Visualization and Bibliometric Analysis of Extracellular Vesicles in Cartilage Regeneration from 2013 to 2023

Visualization and Bibliometric Analysis of Extracellular Vesicles in Cartilage Regeneration from 2013 to 2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Visualization and Bibliometric Analysis of Extracellular Vesicles in Cartilage Regeneration from 2013 to 2023 Shicheng Jia, Tianze Gao, Ruiyang Zhang, Jiayou Chen, Rongji Liang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4162009/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: This study aims to elucidate emerging trends, dynamic advancements, and research focal points in exosome-mediated repair and regeneration of cartilage damage over the past decade, employing a visualization approach. Methods: A total of 300 research records focusing on the utilization of exosomes in cartilage damage repair and regeneration were systematically gathered from the Web of Science Core Collection (WoSCC) database spanning the years 2013 to 2023. Utilizing R language, VOSviewer, CiteSpace, and GraphpadPrism software, we conducted analyses on the general features, historical progression, literature, and keywords of this research domain. Ultimately, we predicted the research focal points and latest trends in the application of exosomes for cartilage defect repair and regeneration. Results: The study amassed a total of 300 articles, revealing a steady increase in publications on exosome application in cartilage repair and regeneration over the years. Significantly, contributions from researchers in China, the USA, and Italy have been pivotal in shaping this field. Keywords clustered into nine distinct research subareas, encompassing mesenchymal stem cells (MSCs), osteochondral repair, runx2, drug delivery, mesenchymal stromal cells, unconventional secretion, biological membranes, and regenerative medicine. Notably, keywords such as "osteochondral repair," "runx2," and "drug delivery" featured prominently between 2013 and 2023. Conclusion: Through a comprehensive review of 300 publications, this bibliometric study provides a detailed overview of exosome-related research in cartilage damage repair and regeneration from 2013 to 2023. The findings contribute to the construction of a knowledge map, illustrating the evolving landscape in this domain. Identifying current trends and potential hotspots, this study offers valuable insights for future researchers in the field. Bibliometric Cartilage regeneration and repair Extracellular vesicles Exosomes Visualization Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Articular cartilage, a layer of connective tissue covering joint surfaces, predominantly comprises chondrocytes and the extracellular matrix they synthesize. Its distinctive biological functions, including robust mechanical properties, result from the specific orientation arrangement of substances such as type 2 collagen and proteoglycans within the extracellular matrix. Unfortunately, when joint cartilage undergoes damage due to factors such as trauma, inflammation, or autoimmunity, its inherent biological functions are compromised. Cartilage defects can escalate to osteoarthritis, precipitating joint pain, stiffness, restricted mobility, and potential disability, posing significant threats to both individual health and societal productivity [ 1 , 2 ]. However, the innate challenge lies in the fact that articular cartilage lacks nerves and blood vessels, rendering its natural repair and regeneration processes exceptionally difficult [ 3 ]. Consequently, the quest to achieve effective repair and regeneration of cartilage defects, aiming to restore the biological properties of compromised cartilage to the greatest extent possible, remains a formidable challenge. Currently, there remains a notable deficiency in effective treatment modalities for the repair and regeneration of joint cartilage defects. Existing surgical interventions for cartilage defects are not without their limitations. While procedures like debridement and microfracture exhibit the ability to repair damaged articular cartilage to some extent, yielding positive short-term clinical outcomes, prolonged postoperative recovery becomes evident in long-term follow-ups. This is primarily due to the repair of fibrocartilage, characterized by inferior mechanical properties and predominant tissue formation [ 4 – 7 ]. Such repair outcomes may result in heightened wear, challenges in bearing joint weight, and inadequate integration with surrounding tissues [ 7 , 8 ]. Autologous cartilage grafting, while initially effective, experiences diminishing efficacy with patient age and an increased number of transplants. Furthermore, it is constrained by factors such as the location, size, and irregular shape of cartilage defects [ 9 , 10 ]. Allogeneic cartilage grafting introduces considerations related to donor availability and the potential for immune rejection [ 9 ]. Although autologous chondrocyte transplantation (ACI) has shown improvements over the aforementioned methods, it extends the treatment timeline due to the necessity for at least two surgeries, imposing a significant physical and psychological burden on patients. In prior endeavors in cartilage tissue engineering, challenges were encountered, notably stemming from insufficient seed cells and the heightened risk of allograft immune rejection. Contemporary research is increasingly directing its focus towards the modulation of the microenvironment post-articular cartilage injury. A current prominent area of investigation involves the establishment of a conducive regenerative microenvironment utilizing acellular scaffolds to stimulate the innate regenerative potential. Extracellular vesicles (EVs), minute particles enveloped by cell membranes and discharged by nearly all cell types, have emerged as a central component in this approach. These vesicles function as messengers for intercellular communication, harboring a diverse array of bioactive molecules, including proteins, enzymes, mRNA, small non-coding RNA, DNA fragments, and metabolic products, on their surface and within their interiors. Through targeted interactions with recipient cells, EVs exert significant influence on cellular behaviors such as proliferation, differentiation, and apoptosis [ 11 ]. Recent studies have provided insights into the presence of EVs in synovial fluid from individuals with osteoarthritis, originating from diverse synovial fibroblasts and immune cells. These EVs exert a notable influence on the advancement of intra-articular inflammation, degradation of the articular cartilage matrix, and apoptosis of chondrocytes [ 12 – 14 ]. In contrast, EVs derived from mesenchymal stem cells (MSCs) exhibit significant immunomodulatory, anti-inflammatory, and anti-aging properties. Investigations have revealed that exosomes obtained from umbilical cord MSCs possess the capacity to enhance the migration and proliferation of bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes. Furthermore, they induce the polarization of macrophages towards the regenerative M2 phenotype. Remarkably, these exosomes contribute to the reversal of chondrocyte aging in osteoarthritis (OA) and the restoration of their vitality. This, in turn, facilitates the establishment of a regenerative microenvironment conducive to cartilage repair [ 15 , 16 ]. Over the past decade, the field of EVs therapy for cartilage repair has witnessed substantial advancements. The combination of various EV types with biomaterials has shown immense potential, emerging as a prominent research focus. Despite this progress, a comprehensive analysis and understanding of publication trends in this area are still lacking. Therefore, it is imperative to conduct an exploration and analysis of the trends in this field to guide future research directions. Bibliometric analysis, employing mathematical and statistical methods to scrutinize publications, offers valuable insights into the developmental history, research focal points, and future trajectories of a specific field. By leveraging visual network tools such as CiteSpace, the R package "bibliometrix," and VOSviewer, researchers can obtain a comprehensive understanding of publication conditions, predict research trends, and identify hotspots. This study performs a novel bibliometric analysis using visual network tools to bridge the knowledge gap and fulfill research needs in the field of EV therapy for cartilage regeneration. The analysis comprehensively examines the literature related to EV therapy for cartilage regeneration from 2013 to 2023, visualizing the developmental trends. It stands as the first scientific and comprehensive analysis of research related to EV therapy for cartilage regeneration, offering insights into the research direction in this field. The significance of this study lies in its addressal of the lack of comprehensive analysis in the field, providing valuable information for researchers. It aids researchers in understanding the current status and hotspots in EV therapy for cartilage regeneration, steering them away from unnecessary detours and enhancing research efficiency. Furthermore, this study guides researchers in formulating reasonable goals and finding suitable research directions. By aggregating big data in the field, this study promotes the sharing of information resources and bolsters researchers' comprehensive capabilities. Methods Data source and search strategy Recognized as one of the most comprehensive and authoritative databases, the Web of Science Core Collection (WoSCC) boasts over 12,000 international academic journals. Hence, it was selected as the primary source to gather global scholarly information for bibliometric analysis, building on previous publications. In this study, we utilized WoSCC to acquire worldwide data for bibliometric analysis. All published articles were systematically retrieved from WoSCC, covering the period from October 1, 2013, to October 1, 2023, with the search conducted on October 4, 2023. Employing the advanced search section function, the search terms were as follows (refer to Fig. 1 ) Theme = Extracellular vesicle or Exosome or Microvesicle or Ectosome or Apoptotic body or Apoptotic bleb or Oncosome AND Theme = Cartilage regeneration or Cartilage repair AND Published year = (2013.10.01–2023.10.01). The exclusion criteria applied in this study were as follows: [ 13 ] Papers that were not categorized as articles or reviews were excluded, and (2) papers not written in English were also excluded. Data collection and statistics We meticulously recorded details of all publications, encompassing nationality, journal name, title, year of publication, author's name, affiliation, funding agency, and research direction. The data was stored in a downloadable format and subsequently imported into Excel 2021 for further analysis. The co-authors independently conducted the search and extraction of data from these studies. Any discrepancies were addressed through consultation with experts, resulting in a final consensus. Subsequently, all data was thoroughly cleansed and analyzed individually by co-authors using GraphPad Prism and Origin 2021. Bibliometric analysis and visualization In our analysis, the number of publications and their citations were directly obtained from WoSCC, and we calculated the relative research interest (RRI) to reflect the ratio of publications in the specific research area each year to the total number of publications in that year. The publishing years were considered from 2013 to 2023, and GraphPad Prism8 was utilized for data analysis. To visualize the global distribution of publications, we utilized R software, including scipy, matplotlib, numpy, and Python, to generate a world map. For an in-depth examination of the total publications from leading countries, we accessed and analyzed data using WoS and GraphPad Prism8. The H-index, serving as a measure of research impact, was analyzed for scholars by GraphPad Prism8. To explore the networks within the literature, VOS viewer was employed to construct literature networks, and analyses of co-citation, co-occurrence, and couple of bibliography were conducted using this software. Visualization of publications and their corresponding relationships between countries was accomplished using R language. For a comprehensive overview of journals, strong citation bursts of keywords and references, and cluster analysis of co-citation of keywords, CiteSpace (6.1.R2) was employed to generate summaries. In summary, a diverse set of software tools, including GraphPad Prism8, VOS viewer, R software, and CiteSpace, were utilized to conduct a comprehensive bibliometric analysis, ensuring a thorough exploration of publications, citations, and networks in the field of interest. Results Overall performance of global literature In accordance with the specified search criteria, a total of 308 studies were initially collected and analyzed spanning the years 2013 to 2023. Following the exclusion of editorial material (4), meeting abstracts (3), and one non-English study, a refined dataset of 300 studies was identified. As depicted in Fig. 2 A, the global literature on this subject exhibited continuous growth from 2013 to 2023, with a particularly pronounced surge in the last 5 years, indicating a rapid upward trajectory. The total number of global studies escalated from 1 in 2013 to 89 in 2022. Notably, the peak year for study publications in the past decade was 2017 (Fig. 2 A). The escalating trend in published literature aligns with an evident increase in research interest in this field over the years (Fig. 2 A). VOSviewer analysis revealed contributions from 50 countries/regions in this field. As illustrated in Fig. 2 C, China emerged as the leading contributor with 161 papers, followed by the USA (36), Italy (20), England (14), and South Korea (14). China accounted for nearly 55% of the total publications among the top 10 countries/regions, with the combined output of the second and third countries, the USA and Italy, amounting to only 22.4% and 12.4% of China's total, respectively. Notably, China has consistently led in publications annually since 2017, underscoring its pivotal role as the primary driving force in advancing this field. In summary, the research on exosome-related cartilage regeneration has garnered increasing attention globally, marking a phase of rapid development and growth. Distribution of publications in countries As depicted in Fig. 3 A, publications with the highest total citation frequencies originated from China (4403), followed by Singapore (1733), the USA (1108), the Netherlands (608), and Iran (448). In terms of relative publications and the H-index, China (35) played a dominant role in this field, followed by the USA (18), Italy (12), Iran (10), and South Korea (9) (Fig. 3 C). Notably, publications from Singapore exhibited the highest average citation frequencies (144.4), followed by the Netherlands (50.6), Iran (34.4), England (30.8), and the USA (30.7) (Fig. 3 B). Analysis of country/regional collaboration The authorship-country collaboration analysis, conducted via VOSviewer (Fig. 4 C), highlighted the United States as the most intensively collaborating nation, boasting a total link strength of 51. This indicates that the USA has the strongest international collaboration in the field. In contrast, despite having the highest research output, China exhibited a considerably lower total link strength of 25, suggesting that the majority of China's research endeavors have been focused on domestic collaboration. In essence, the USA and China hold prominent positions in international cooperation, with other countries also engaging in collaboration, albeit to a lesser extent and often not as closely interconnected as their collaborations with the United States and China. Analysis of institutions In terms of publication ranking, Table 1 lists the top 10 contributing institutions, with Shanghai Jiao Tong University being the leading contributor in terms of the number of articles. When examining international collaboration between institutions, the top institution was Future Biol (Fig. 4 D). Interestingly, institutions from China accumulated the highest number of citations, yet none of them ranked prominently in the collaboration rankings. This suggests that Chinese institutions demonstrated a stronger inclination towards domestic cooperation, consistent with the analysis of country collaboration. Utilizing VOSviewer (Fig. 4 B), the impact of each research was estimated based on citations, considering the citations in the top 20 institutions. In this context, Sichuan University emerged as the institution with the highest impact (link strength 18985), followed by Shanghai Jiao Tong University (link strength 16698), and the National University of Singapore (link strength 13467). Notably, Sichuan University, despite not having the highest research output, demonstrated a relatively strong research impact. Table 1 The top 10 institutions published literature related to EVs for cartilage regeneration from 2013 to 2023. Rank Institution Article counts Percentage Country 1 Shanghai Jiao Tong University 16 5.333 China 2 Sichuan University 14 4.667 China 3 National University of Singapore 12 4 Singapore 4 Tongji University 11 3.667 China 5 Chinese People S Liberation Army General Hospital 9 3 China 6 Nanjing Medical University 9 3 China 7 Zhejiang University 9 3 China 8 Irccs Istituto Ortopedico Galeazzi 8 2.667 Italy 9 Peking University 8 2.667 China 10 Sun Yat Sen University 8 2.667 China Table 2 The top 10 well-represented research areas. Rank Research Areas Records Percentage 1 Cell Biology 95 31.67 2 Materials Science 47 15.67 3 Research Experimental Medicine 46 15.33 4 Biotechnology Applied Microbiology 43 14.33 5 Science Technology Other Topics 43 14.33 6 Biochemistry Molecular Biology 42 14.00 7 Engineering 40 13.33 8 Pharmacology Pharmacy 30 10.00 9 Orthopedics 29 9.67 10 Chemistry 27 9.00 Table 3 The top 10 funds related to EVs for cartilage regeneration from 2013 to 2023. Rank Journal Article counts Percentage 1 National Natural Science Foundation of China Nsfc 100 33.33 2 National Institutes of Health Nih Usa 15 5.00 3 United States Department Of Health Human Services 15 5.00 4 Uk Research Innovation Ukri 14 4.67 5 China Postdoctoral Science Foundation 12 4.00 6 National Key R D Program of China 11 3.67 7 Medical Research Council Uk Mrc 10 3.33 8 Beijing Natural Science Foundation 7 2.33 7 European Union Eu 7 2.33 10 Ministry of Health Italy 7 2.33 Analysis of authors In total, 152 authors in the field, each having published more than 2 articles, were considered and analyzed using VOSviewer. The collaboration analysis assessed the relatedness of authors based on the number of articles they co-authored. The top 5 authors with the most publications EVs for cartilage regeneration were Toh, Wei Seong; Ragni, Enrico; De Girolamo, LAURA; Lim, Sai Kiang; and Orfei, Carlotta Perucca (Table 5 ). Toh, Wei Seong, in particular, published 9 articles with 1144 citations, indicating a significant contribution and leading role in the field from both publication and citation perspectives. The visualization of author collaboration in VOSviewer (Fig. 5 B) revealed the existence of two collaboration circles of researchers. Bibliographic coupling analysis and co-citation analysis of authors are presented in Fig. 5 A and 5 C, respectively. The link strength between two authors signifies the correlation of their research fields. The results indicate that Zhang, SP, and Toh, Wei Seong, are the authors with the highest link strength, indicating that their research findings are widely recognized in the field. Table 4 The top 10 most productive journals related to EVs for cartilage regeneration from 2013 to 2023. Rank Journal Article counts Percentage Impact factor (IF, 2022) 1 Frontiers in Bioengineering and Biotechnology 17 5.67 5.7 2 Frontiers in Cell and Developmental Biology 12 4.00 5.5 3 International Journal of Molecular Sciences 11 3.67 5.6 4 Stem Cell Research Therapy 11 3.67 7.5 5 Cells 9 3.00 6.0 6 Journal of Nanobiotechnology 7 2.33 10.2 7 Stem Cells International 7 2.33 4.3 8 Biomedicines 6 2.00 4.7 7 Cartilage 6 2.00 2.8 10 Journal of Orthopaedic Translation 6 2.00 6.6 Table 5 The top 10 authors with the most publications on EVs for cartilage regeneration from 2013 to 2023. Rank Highly Published Authors Article counts percentage 1 Toh, Wei Seong 9 3.00 2 Ragni, Enrico 7 2.33 3 De Girolamo, LAURA 7 2.33 4 Lim, Sai Kiang 7 2.33 5 Orfei, Carlotta Perucca 6 2.00 6 Hui, James Hoi Po 6 2.00 7 Lai, Ruenn Chai 6 2.00 8 Zhang, Shipin 5 1.67 9 Colombini, Alessandra 4 1.33 10 Yin, Feng 4 1.33 Citation burst, reflecting the references of interest to researchers in a specific period, is also an important indicator. In our analysis, the top strongest citation bursts were identified. Specifically, CiteSpace summarized a total of 20 publications, presented in Fig. 5 D. The study by Zhang S maintained the strongest citation burst with a strength of 9.69, lasting from 2017 to 2019. Analysis of research areas and journals The 10 most productive journals in this study are presented in Table 4 . Frontiers in Bioengineering and Biotechnology emerged as the leading journal, publishing 17 articles. Other notable journals include Frontiers in Cell and Developmental Biology (12 publications), International Journal of Molecular Sciences (11 publications), Stem Cell Research Therapy (11 publications), and Cells (9 publications). In terms of co-citation analysis using VOSviewer, journals with fewer than 10 citations were excluded. As visualized in Fig. 6 , a total of 251 journals were analyzed for total link strength. The top 5 journals with the highest total link strength were Stem Cell Research Therapy (total citations = 1080), Biomaterials (total citations = 841), Osteoarthritis and Cartilage (total citations = 811), SCI REP-UK (total citations = 554), and J Extracell Vesicles (total citations = 572), as detailed in Table 5 . A summary of research orientations, generated using VOSviewer, is presented in Table 2 . The most prevalent research fields include Cell Biology, Materials Science, Experimental Medicine, Biotechnology, and Applied Microbiology, as well as Science Technology Other Topics. These research orientations provide insights into the current focus and potential areas of development in the field. Analysis of references and funds To identify the most influential literature, co-citation references were analyzed using VOSviewer (Fig. 7 A). The article by Tao Sc had the highest link strength. The references were clustered into four main groups: mesenchymal stem cell, critical-sized, exosome, and bone regeneration (Fig. 7 B). Additionally, the top 5 research articles with the most citations in the field of EVs for cartilage regeneration are shown in Table 6 and Table 7 . The article titled "MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis, and modulating immune reactivity" was the most cited research article, with 509 citations. The article titled "MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment" was the most cited review article, with 295 citations. Furthermore, Fig. 7 C provides more details on related articles, including the citation burst for each reference. The paper by Zhou Y, published in 2013, had the strongest citation burst, lasting from 2015 to 2017. Table 6 The top 5 research articles with the most citations in the field of EVs for cartilage regeneration from 2013 to 2023. Rank Title First author Journal IF Publication year Total citations 1 MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity Zhang, SP Biomaterials 14.0 2018 509 2 Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration Zhang, S Osteoarthritis and Cartilage 7.0 2016 419 3 Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration Liu, XL Nanoscale 6.7 2017 280 4 MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis Zhang, SP Biomaterials 14 2019 275 5 Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A Mao, GP Stem Cell Research & Therapy 7.5 2018 255 Table 7 The top 5 review articles with the most citations in the field of EVs for cartilage regeneration from 2013 to 2023. Rank Title First author Journal IF Publication year Total citations 1 MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment Toh, WS Seminars in Cell & Developmental Biology 7.3 2017 295 2 Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine - a new paradigm for tissue repair Bjorge, IM Biomaterials Science 6.6 2017 177 3 Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis? Mianehsaz, E Stem Cell Research & Therapy 7.5 2019 148 4 Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives Lee, WYW Journal of Orthopaedic Translation 6.6 2017 136 5 Macrophages: The Good, the Bad, and the Gluttony Ross, ERA Frontiers in Immunology 7.3 2021 126 A list of funding sources for EVs in cartilage regeneration is summarized in Table 3 . According to the table, the National Natural Science Foundation of China supported the highest number of articles (100 articles), followed by the National Institutes of Health (15 articles) and the United States Department of Health and Human Services (15 articles). Interestingly, the top three funding sources supporting the most articles are from China and the United States, consistent with previous analyses of countries.. Analysis of keywords and hotspots Using VOSviewer's algorithm, the burst of keywords based on burst detection was analyzed and visualized. The co-occurrence analysis of keywords is displayed in Fig. 8 A and 8 B, with the keyword "osteoarthritis" having the highest link strength, indicating a significant focus on EVs therapies in osteoarthritis. The keywords were primarily grouped into nine categories and arranged in a timeline. Notably, "mesenchymal stem cells" has been a topic of interest for researchers for many years, indicating that EVs derived from MSCs are hotspots in cartilage regeneration. Furthermore, keywords such as "osteochondral repair," "runx2," and "drug delivery" have also frequently appeared during the period of 2013–2023. This suggests ongoing research interest and emphasis on these specific aspects in the field of EV therapies for cartilage regeneration. Discussion Over the past decade, substantial efforts have been dedicated to exploring the application of extracellular vesicles for cartilage repair and regeneration. This study contributes a comprehensive bibliometric and visualization analysis covering the period from 2013 to 2023. The utilization of bibliometric software has become increasingly prevalent, offering a valuable tool for researchers. Bibliometric analysis facilitates an intuitive and systematic understanding of the development process and trends within a specific field. Moreover, it aids in the identification of emerging research hotspots and achievements, providing valuable insights for both novices and seasoned researchers alike. Trends of global development of EVs for cartilage repair and regeneration As evident from the visualized figures, there is a notable upward trend in the number of publications from October 1, 2013, to October 1, 2023. Concurrently, the relative research interest has also seen a surge in recent years, indicating a growing popularity in this field. Regarding national contributions, China has emerged as the leader with over 100 publications, making it the highest contributor over the past decade, followed by the United States and Italy. China also leads in terms of the total number of citations and the highest H-index of related publications. However, when considering average citations, Singapore surpasses all other countries, with China ranking sixth. These findings suggest that while China has a significant influence in this field and produces high-quality research, there is room for improvement in the average quality of academic publications. Eight of the top 10 institutions in terms of the number of publications are from China, and four of the top 10 funding sources in the field are also from China, with the first place belonging to China. This highlights the close relationship between China's high academic influence globally and the support from research platforms and funds. Furthermore, the backing of research platforms and funding serves as the foundation for conducting impactful research. As the field continues to advance, collaboration among nations, institutions, and researchers is expected to intensify, catalyzing further breakthroughs and innovations in the application of EVs for cartilage repair and regeneration. This global trajectory promises a future where EV-based therapies play a pivotal role in enhancing the clinical outcomes of individuals grappling with cartilage-related disorders. Status of authors and studies In contrast to the country-based publication trends, authors from Singapore emerge as prominent contributors with the highest individual article count and the highest representation in the top 10 prolific authors, surpassing even their Italian counterparts. Moreover, Singaporean authors exhibit notable collaboration and are cited most frequently in related publications, indicating a focused and advanced exploration of EVs applications in cartilage defect repair and regeneration within the scholarly community of Singapore. In-depth investigations by Italian researchers are also evident. Conversely, China would benefit from an increased concentration of researchers specializing in this domain. Examining specific publications, the most cited primary authors in both review and research literature are Singaporean scholars, Zhang, SP, and Toh, WS, respectively. Their research findings, notably Zhang's accomplishment in achieving osteochondral regeneration using exosomes derived from bone marrow mesenchymal stem cells, have garnered widespread recognition [ 17 ]. This study demonstrates that exosomal CD73 facilitates cell migration and proliferation by activating the AKT and ERK signaling pathways. Furthermore, exosome-treated cartilage defects exhibit a regenerative immunophenotype characterized by high M2 macrophage infiltration and low IL-1b and TNF-a expression. Beyond author analysis, this study delves into the prevailing research landscape based on published journals. Noteworthy publications in this field predominantly appear in journals such as Frontiers in Bioengineering and Biotechnology, Frontiers in Cell and Developmental Biology, and the International Journal of Molecular Sciences. The listed journals in Table 4 provide insights into current research hotspots and directions. Additionally, journal-based citation analysis identifies Stem Cell Research & Therapy (IF = 7.5) as the most cited journal, signifying its significant contribution to the field. Analysis of research hotspots The research trends and frontiers in EVs for cartilage defect repair and regeneration are elucidated through keyword analysis. Figure 8 A and B highlight "Osteoarthritis" as the keyword with the highest frequency in publications, indicating that the primary focus of current research lies in understanding the role and therapeutic potential of EVs in osteoarthritis [ 18 – 21 ]. A visual analysis of keyword clustering identifies nine main research clusters, shedding light on promising hotspots in the field. These clusters likely represent distinct areas of investigation and innovation within the application of EVs for cartilage repair and regeneration. MSCs stand out as a significant research cluster, emphasizing the pluripotent nature of these stem cells and their ability to release bioregulatory nucleic acids and proteins via EVs [ 22 – 24 ]. This suggests a growing interest in utilizing EV-based therapies as an alternative to traditional stem cell approaches for cartilage repair [ 17 , 25 – 27 ]. Given that extracellular vesicles essentially comprise cell-derived biological membranes, facilitating substance exchange between cells and participating in diverse physiological and pathological processes [ 28 ], their free entry and exit properties could be harnessed for efficient drug delivery, thereby enhancing drug action efficacy [ 29 , 30 ]. EVs present opportunities to regulate various stages of pathological changes after cartilage injury. By understanding and manipulating the content of EVs, researchers aim to achieve precise and targeted regulation, potentially influencing signaling pathways like Wnt and AKT [ 31 , 32 ]. The immunomodulatory functions of EVs, particularly in the regulation of macrophage polarization and the transformation of dendritic cells and Treg cells, are garnering attention [ 23 , 33 – 35 ]. This suggests a focus on understanding the immune response and its modulation for effective cartilage regeneration. Future studies are anticipated to delve deeper into the mechanisms through which EVs contribute to cartilage defect repair [ 36 ]. This reflects a desire for a comprehensive understanding of the cellular and molecular processes involved, enabling more precise interventions. In summary, the research hotspots in the field of EVs for cartilage defect repair and regeneration encompass osteoarthritis, MSCs, biological membranes, drug delivery, regulation of pathological changes, immunomodulation, and the exploration of underlying mechanisms. These trends highlight the multidimensional approach researchers are taking to harness the therapeutic potential of EVs in addressing cartilage injuries. Prospects for EVs in cartilage regeneration Articular cartilage presents challenges in repair post-defect due to its absence of structural features like blood vessels and nerves. The excessive inflammatory response post-cartilage defect triggers various degrading enzymes, including MMPs, ADAMTS, leading to increased catabolism of the cartilage matrix. EVs have emerged as promising players in the realm of cartilage regeneration, offering novel therapeutic avenues for addressing the challenges associated with cartilage defects and osteoarthritis. Deepening the application of extracellular vesicles to regulate different stages of pathological changes after cartilage injury offers a pathway for cartilage defect repair and regeneration. As we delve into the prospects for EVs in cartilage regeneration, it becomes evident that these nanosized vesicles hold immense potential for revolutionizing the field of regenerative medicine. One of the key prospects lies in the regenerative capabilities inherent in EVs derived from various cell sources, particularly MSCs. MSC-derived EVs have been shown to carry a cargo of bioactive molecules, including proteins, nucleic acids, and microRNAs, capable of modulating cellular activities crucial for cartilage repair [ 37 ]. The paracrine effects mediated by MSC-derived EVs play a pivotal role in promoting cell proliferation, attenuating apoptosis, and orchestrating anti-inflammatory responses within the damaged cartilage microenvironment. Moreover, EVs present a unique advantage in terms of their natural composition, mimicking the cell membrane and facilitating biocompatibility. This characteristic makes EVs an attractive alternative to traditional cell-based therapies, offering a cell-free approach to cartilage regeneration [ 38 ]. The capacity of EVs to traverse biological barriers, including the blood-brain barrier, enhances their therapeutic potential, allowing for targeted and minimally invasive interventions. The versatility of EVs extends to their immunomodulatory properties, influencing the behavior of immune cells involved in the inflammatory response associated with cartilage injuries. By promoting the polarization of macrophages toward anti-inflammatory phenotypes and regulating immune cell activities, EVs contribute to the creation of a favorable microenvironment for cartilage regeneration. Moreover, exosomes derived from mesenchymal stem cells contain a variety of miRNAs and proteins with immunomodulatory functions, regulating macrophage polarization to the M2 phenotype and promoting the transformation of tolerant dendritic cells and Treg cells [ 39 – 41 ]. Furthermore, ongoing research is unraveling the potential of engineered EVs, designed to carry specific therapeutic payloads [ 42 ]. These designer EVs can be tailored to enhance their regenerative capabilities, delivering targeted growth factors, signaling molecules, or gene therapies directly to the site of cartilage damage [ 43 ]. This opens new avenues for precision medicine in cartilage regeneration, allowing for customized therapeutic interventions based on the unique characteristics of each patient's condition. Despite the optimistic prospects, challenges remain, such as standardizing isolation techniques, understanding the optimal dosage and timing of EV administration, and ensuring long-term efficacy. Additionally, regulatory frameworks must evolve to accommodate the unique nature of EV-based therapies. Collaborative efforts between researchers, clinicians, and regulatory bodies are essential to navigate these challenges and translate the prospects of EVs in cartilage regeneration from the laboratory to clinical practice. Future studies can explore the mechanisms of extracellular vesicles in cartilage defect repair for precise and targeted regulation. In conclusion, the prospects for EVs in cartilage regeneration are marked by their regenerative, biocompatible, and immunomodulatory properties. As research advances, harnessing the full potential of EVs holds the key to unlocking innovative and effective therapies for cartilage defects, providing hope for millions of individuals suffering from osteoarthritis and related conditions. The journey from discovery to clinical application represents a paradigm shift in regenerative medicine, with EVs poised to reshape the landscape of cartilage regeneration in the years to come. Conclusion Through a comprehensive analysis of 300 publications, this bibliometric study provides a detailed overview of exosome-related research in cartilage damage repair and regeneration from 2013 to 2023. The findings contribute to the construction of a knowledge map, illustrating the evolving landscape in this domain. Identifying current trends and potential hotspots, this study offers valuable insights for future researchers in the field. Abbreviations ADAMTS, A disintegrin and metalloproteinase with thrombospondin; BMSCs, bone marrow-derived mesenchymal stem cells; ACI, autologous chondrocyte transplantation; EVs, extracellular vesicles; MMPs, matrix metalloproteinases; MSCs, mesenchymal stem cells; OA, osteoarthritis; RRI, relative research interest; WoSCC, Web of Science Core Collection. Declarations Ethics approval and consent to participate: The authors declare there are no needs to get ethics approval and consent to participate in this study. Consent for publication: The authors declare there are no needs to get ethics approval and consent to participate in this study. Not applicable. Availability of data and materials: Not acceptable. Authors' contributions: Authors' agreement: Shicheng Jia designed the project, determined search formula, performed the experiments, and corrected the draft. Tianze Gao and Ruiyang Zhang wrote the paper draft, analyzed, and visualized data. Jiayou ChenandRongji Liang managed the publications, drew the tables and figures. Yuxiang Ren and Xiaocheng Jiang supervised the experimentations. Jianjing Lin provided financial support and ensured the final manuscript. All authors have read and approved the final version of the manuscript. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy. Funding: This study was funded by Shenzhen“San-Ming” Project of Medicine (No. SZSM202211019), Guangdong Basic and Applied Basic Research Foundation (2022A1515220056) and Shenzhen Science and Technology Innovation Committee Foundation (JCYJ20220530160212028). Declarations of competing interests: The authors declare that they have no financial competing interests exist. Acknowledgement: No acknowledgement. References X. Tang, S. Wang, S. Zhan, J. Niu, K. Tao, Y. Zhang, J. Lin, The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study, Arthritis Rheumatol, 68 (2016) 648-653. J. Martel-Pelletier, A.J. Barr, F.M. Cicuttini, P.G. Conaghan, C. Cooper, M.B. Goldring, S.R. Goldring, G. Jones, A.J. Teichtahl, J.-P. Pelletier, Osteoarthritis, Nature Reviews Disease Primers, 2 (2016) 16072. A.J. Sophia Fox, A. Bedi, S.A. Rodeo, The Basic Science of Articular Cartilage: Structure, Composition, and Function, Sports Health: A Multidisciplinary Approach, 1 (2009) 461-468. L. Zhou, V.O. Gjvm, J. Malda, M.J. Stoddart, Y. Lai, R.G. Richards, K. Ki-Wai Ho, L. Qin, Innovative Tissue-Engineered Strategies for Osteochondral Defect Repai r and Regeneration: Current Progress and Challenges, Advanced healthcare materials, (2020). C. Lesage, M. Lafont, P. Guihard, P. Weiss, J. Guicheux, V. Delplace, Material‐Assisted Strategies for Osteochondral Defect Repair, Advanced Science, 9 (2022) 2200050. D. Sun, X. Liu, L. Xu, Y. Meng, H. Kang, Z. Li, Advances in the Treatment of Partial-Thickness Cartilage Defect, International Journal of Nanomedicine, Volume 17 (2022) 6275-6287. C.L. Camp, M.J. Stuart, A.J. Krych, Current Concepts of Articular Cartilage Restoration Techniques in the Knee, Sports Health: A Multidisciplinary Approach, 6 (2013) 265-273. R.S. Tuan, A.F. Chen, B.A. Klatt, Cartilage Regeneration, J. Am. Acad. Orthop. Surg., 21 (2013) 303-311. G. Filardo, L. Andriolo, F. Soler, M. Berruto, P. Ferrua, P. Verdonk, F. Rongieras, D.C. Crawford, Treatment of unstable knee osteochondritis dissecans in the young adul t: results and limitations of surgical strategies-The advantages of al lografts to address an osteochondral challenge, Knee surgery, sports traumatology, arthroscopy : official journal of t he ESSKA, 27 (2018) 1726-1738. S. Imade, N. Kumahashi, S. Kuwata, J. Iwasa, Y. Uchio, Effectiveness and limitations of autologous osteochondral grafting for the treatment of articular cartilage defects in the knee, Knee surgery, sports traumatology, arthroscopy : official journal of t he ESSKA, 20 (2011) 160-165. J. Malda, J. Boere, C.H.A. van de Lest, P.R. van Weeren, M.H.M. Wauben, Extracellular vesicles — new tool for joint repair and regeneration, Nature Reviews Rheumatology, 12 (2016) 243-249. R.J. Berckmans, R. Nieuwland, M.C. Kraan, M.C.L. Schaap, D. Pots, T.J.M. Smeets, A. Sturk, P.P. Tak, Synovial microparticles from arthritic patients modulate chemokine and cytokine release by synoviocytes, Arthritis Research & Therapy, 7 (2005) R536-R544. T. Kato1, S. Miyaki, H. Ishitobi, Y. Nakamura1, T. Nakasa1, M.K. Lotz, M. Ochi, Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes., Arthritis Research & Therapy 16 (2014) R163. J.r.H.W. Distler, A.J. ngel, L.C. Huber, C.A. Seemayer, C.F.R. III, R.E. Gay, B.A. Michel, A. Fontana, S. Gay, D.S. Pisetsky, O. Distler, The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles, Proceedings of the National Academy of Sciences of the United States of America, 102 (2005) 2892-2897. H. Cao, M. Chen, X. Cui, Y. Liu, Y. Liu, S. Deng, T. Yuan, Y. Fan, Q. Wang, X. Zhang, Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes, ACS Nano, 17 (2023) 13358-13376. S. Jiang, G. Tian, Z. Yang, X. Gao, F. Wang, J. Li, Z. Tian, B. Huang, F. Wei, X. Sang, L. Shao, J. Zhou, Z. Wang, S. Liu, X. Sui, Q. Guo, W. Guo, X. Li, Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration, Bioactive Materials, 6 (2021) 2711-2728. S. Zhang, S.J. Chuah, R.C. Lai, J.H.P. Hui, S.K. Lim, W.S. Toh, MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity, Biomaterials, 156 (2018) 16-27. B. You, C. Zhou, Y. Yang, MSC-EVs alleviate osteoarthritis by regulating microenvironmental cells in the articular cavity and maintaining cartilage matrix homeostasis, Ageing Research Reviews, 85 (2023) 101864. Z. Liu, Y. Zhuang, L. Fang, C. Yuan, X. Wang, K. Lin, Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis, Bioactive Materials, 22 (2023) 423-452. H. Yin, M. Li, G. Tian, Y. Ma, C. Ning, Z. Yan, J. Wu, Q. Ge, X. Sui, S. Liu, J. Zheng, W. Guo, Q. Guo, The role of extracellular vesicles in osteoarthritis treatment via microenvironment regulation, Biomaterials Research, 26 (2022) 52. B. Yin, J. Ni, C.E. Witherel, M. Yang, J.A. Burdick, C. Wen, S.H.D. Wong, Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics, Theranostics, 12 (2022) 207-231. X. Zhao, Y. Zhao, X. Sun, Y. Xing, X. Wang, Q. Yang, Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis, Frontiers in Bioengineering and Biotechnology, 8 (2020) 575057. K. Li, G. Yan, H. Huang, M. Zheng, K. Ma, X. Cui, D. Lu, L. Zheng, B. Zhu, J. Cheng, J. Zhao, Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages, Journal of Nanobiotechnology, 20 (2022) 38. G. Qiu, G. Zheng, M. Ge, J. Wang, R. Huang, Q. Shu, J. Xu, Functional proteins of mesenchymal stem cell-derived extracellular vesicles, Stem Cell. Res. Ther., 10 (2019) 359. C.H. Woo, H.K. Kim, G.Y. Jung, Y.J. Jung, K.S. Lee, Y.E. Yun, J. Han, J. Lee, W.S. Kim, J.S. Choi, S. Yang, J.H. Park, D.G. Jo, Y.W. Cho, Small extracellular vesicles from human adipose‐derived stem cells attenuate cartilage degeneration, Journal of Extracellular Vesicles, 9 (2020) 1735249. S. Li, J. Liu, S. Liu, W. Jiao, X. Wang, Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis, Journal of Nanobiotechnology, 19 (2021) 343. S. Keshtkar, N. Azarpira, M.H. Ghahremani, Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine, Stem Cell. Res. Ther., 9 (2018) 63. G. van Niel, G. D'Angelo, G. Raposo, Shedding light on the cell biology of extracellular vesicles, Nature reviews. Molecular cell biology, 19 (2018) 213-228. P. Vader, E.A. Mol, G. Pasterkamp, R.M. Schiffelers, Extracellular vesicles for drug delivery, Adv. Drug Del. Rev., 106 (2016) 148-156. S. Li, S. Stöckl, C. Lukas, M. Herrmann, C. Brochhausen, M.A. König, B. Johnstone, S. Grässel, Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p, Stem Cell. Res. Ther., 12 (2021) 252. H. Hu, L. Dong, Z. Bu, Y. Shen, J. Luo, H. Zhang, S. Zhao, F. Lv, Z. Liu, miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration, Journal of Extracellular Vesicles, 9 (2020) 1778883. B.L. Thomas, S.E. Eldridge, B. Nosrati, M. Alvarez, A.S. Thorup, G. Nalesso, S. Caxaria, A. Barawi, J.G. Nicholson, M. Perretti, C. Gaston‐Massuet, C. Pitzalis, A. Maloney, A. Moore, R. Jupp, F. Dell'Accio, WNT3A‐loaded exosomes enable cartilage repair, Journal of Extracellular Vesicles, 10 (2021) e12088. P. Lai, J. Weng, L. Guo, X. Chen, X. Du, Novel insights into MSC-EVs therapy for immune diseases, Biomarker Research, 7 (2019). R. Wu, X. Fan, Y. Wang, M. Shen, Y. Zheng, S. Zhao, L. Yang, Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy, Front. Immunol., 13 (2022). E.I. Buzas, The roles of extracellular vesicles in the immune system, Nature Reviews Immunology, 23 (2022) 236-250. Y. Sun, J. Zhao, Q. Wu, Y. Zhang, Y. You, W. Jiang, K. Dai, Chondrogenic primed extracellular vesicles activate miR-455/SOX11/FOXO axis for cartilage regeneration and osteoarthritis treatment, npj Regenerative Medicine, 7 (2022) 53. S. Yuan, G. Li, J. Zhang, X. Chen, J. Su, F. Zhou, Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis, Pharmaceutics, 15 (2023) 1814. S. Rani, A.E. Ryan, M.D. Griffin, T. Ritter, Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications, Mol. Ther., 23 (2015) 812-823. C.R. Harrell, N. Jovicic, V. Djonov, N. Arsenijevic, V. Volarevic, Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases, Cells, 8 (2019) 1605-1626. E. Ragni, C. Perucca Orfei, F. Sinigaglia, L. de Girolamo, Joint Tissue Protective and Immune-Modulating miRNA Landscape of Mesenchymal Stromal Cell-Derived Extracellular Vesicles under Different Osteoarthritis-Mimicking Conditions, Pharmaceutics, 14 (2022) 1400. H. Zhou, X. Shen, C. Yan, W. Xiong, Z. Ma, Z. Tan, J. Wang, Y. Li, J. Liu, A. Duan, F. Liu, Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage, Stem Cell. Res. Ther., 13 (2022) 322. J. Rädler, D. Gupta, A. Zickler, S.E. Andaloussi, Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading, Molecular therapy : the journal of the American Society of Gene Therap y, 31 (2023) 1231-1250. M.J.W. Evers, S.I. van de Wakker, E.M. de Groot, O.G. de Jong, J.J.J. Gitz-François, C.S. Seinen, J.P.G. Sluijter, R.M. Schiffelers, P. Vader, Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nan oparticles, Advanced healthcare materials, 11 (2022) e2101202. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4162009","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":284132586,"identity":"bd93077a-a168-4ed3-9999-f722f07db7c3","order_by":0,"name":"Shicheng Jia","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shicheng","middleName":"","lastName":"Jia","suffix":""},{"id":284132587,"identity":"15c902f1-fa93-4faf-9c5c-f8b9a99e0216","order_by":1,"name":"Tianze Gao","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tianze","middleName":"","lastName":"Gao","suffix":""},{"id":284132588,"identity":"e5803e46-20fb-4780-a0e6-3f9e71326763","order_by":2,"name":"Ruiyang Zhang","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ruiyang","middleName":"","lastName":"Zhang","suffix":""},{"id":284132589,"identity":"0c7aed2f-2600-48e4-b3e2-45b183ac02cb","order_by":3,"name":"Jiayou Chen","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiayou","middleName":"","lastName":"Chen","suffix":""},{"id":284132590,"identity":"b4cb040f-ce06-4779-9865-898a176a2c97","order_by":4,"name":"Rongji Liang","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rongji","middleName":"","lastName":"Liang","suffix":""},{"id":284132591,"identity":"af189632-0393-4d79-8a21-1436abbdb41c","order_by":5,"name":"Yuxiang Ren","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuxiang","middleName":"","lastName":"Ren","suffix":""},{"id":284132592,"identity":"ca48f09a-a160-48d9-ae7d-1177fddef1c7","order_by":6,"name":"Xiaocheng Jiang","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaocheng","middleName":"","lastName":"Jiang","suffix":""},{"id":284132593,"identity":"3f4129c5-0787-48c0-b000-5d843e245ed2","order_by":7,"name":"Jianjing Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYBACPmYGBoMEBgZmNgYGxscMPGBBA7xa2JC0MBsTpwWZLQ1lENDCznug4EHNHXY+6fZr1QUy2xIb2Ju3STDU3MHjML4Eg4Rjz5jZZM6U3Z7BczuxgedYmQTDsWd4tPAYGCSwHWZmk8hJu80D0iKRYybB2HCYgJZ/EC3FYC3yb4jQktgG0pJ+jBliCw8xWvrAtjBLA/1i3MaTVmyRcAy3Fn7+M2aGP74dTpafkf7wc2HPbdl+9sMbb3yowa0FZBEoGpIZGHgMGBh7oDGVgE8DMNIfAAk7BgZ2IP0Dv9JRMApGwSgYmQAAme5J5mRcc68AAAAASUVORK5CYII=","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jianjing","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2024-03-25 09:05:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4162009/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4162009/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53649598,"identity":"c3146444-07d7-4ff5-bd5a-971a8b9dc7bb","added_by":"auto","created_at":"2024-03-28 14:28:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":410941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart depicting the literatures selection process.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"FigurePage1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/47bb42a5302ccd5a56898271.jpg"},{"id":53649599,"identity":"0be16c88-359e-416f-b327-ce9809ecc0c8","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1386698,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGlobal trends and countries/regions contributing to the research field regarding EVs for cartilage regeneration from 2013 to 2023. (A)\u003c/strong\u003e The annual number of publications related to EVs for cartilage regeneration from 2013 to 2023. \u003cstrong\u003e(B) \u003c/strong\u003eA world map depicting the distribution of EVs for cartilage regeneration from 2013 to 2023. The total number \u003cstrong\u003e(C)\u003c/strong\u003e and annual number \u003cstrong\u003e(D) \u003c/strong\u003eof publications in the top 10 most productive countries from 2013 to 2023.\u003c/p\u003e","description":"","filename":"FigurePage2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/1c88a8bfc6d64cac38c79ddc.jpg"},{"id":53650321,"identity":"9425047e-1bb1-4441-b062-8da2e9b75d5b","added_by":"auto","created_at":"2024-03-28 14:36:05","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":628626,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e The top 10 countries/regions of total citations regarding EVs for cartilage regeneration from 2013 to 2023.\u003cstrong\u003e (B)\u003c/strong\u003e The top 10 countries/regions of the average citations per publication related to EVs for cartilage regeneration from 2013 to 2023.\u003cstrong\u003e (C)\u003c/strong\u003e The top 10 countries/regions of the publication H-index related to EVs forcartilage regeneration from 2013 to 2023.\u003c/p\u003e","description":"","filename":"FigurePage3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/9d46a20e24bb663fafb2b272.jpg"},{"id":53649601,"identity":"d8ab1289-e1d4-47e3-9d54-0f8e2dfdf823","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1702744,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMapping of countries/regions/institutions associated with EVs forcartilageregeneration from 2013 to 2023. (A)\u003c/strong\u003eCountry/regional collaboration analysis derived based on Vosviewer.\u003cstrong\u003e (B)\u003c/strong\u003eInstitutional collaboration analysis based on Vosviewer. \u003cstrong\u003e(C) \u003c/strong\u003eThe authorship-country collaboration analysis via Vosviewer. \u003cstrong\u003e(D)\u003c/strong\u003e The authorship-institution collaboration analysis via Vosviewer. The nodes represent countries/regions, and the lines connect them. The number of publications grows proportionally to the size of the nodes. The lines between the nodes represent the cooperation relationship, and the thickness of the connecting lines represents the strength of their cooperation; the closer the cooperationis, the thicker the connecting lines.\u003c/p\u003e","description":"","filename":"FigurePage4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/1738455d4b9501f3c0a2ca27.jpg"},{"id":53649606,"identity":"aaf7d0e5-2342-47ae-b101-d9d729159110","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1416473,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNetwork visualization of author collaboration analysis regarding EVs for cartilageregeneration from 2013 to 2023. (A) \u003c/strong\u003eAuthor collaboration analyzed by Vosviewer. \u003cstrong\u003e(B) \u003c/strong\u003eNetwork visualization diagram of authorship-author analysis based on Vosviewer. \u003cstrong\u003e(C) \u003c/strong\u003eNetwork visualization diagram of cocited-author analysis based on Vosviewer.\u003cstrong\u003e (D)\u003c/strong\u003e Top 20 cited authors with the strongest citation bursts of publications related to EVs for cartilage regeneration. Author collaboration authors are indicated by the node. The collaboration relationship is indicated by the line connecting the nodes. The node area grows as the number of collaborations increases.\u003c/p\u003e","description":"","filename":"FigurePage5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/72ea87e6365f748c31e77aa5.jpg"},{"id":53649604,"identity":"bbdd1976-9c15-44fc-83ba-2280fc5a3610","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":15232389,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eArticles published in different journals on EVs for cartilage regeneration from 2013 to 2023. (A)\u003c/strong\u003e The dual-map overlay of journals related to EVs for cartilage regeneration.\u003cstrong\u003e (B) \u003c/strong\u003eBibliographic analysis of journals based on Vosviewer.\u003cstrong\u003e (C) \u003c/strong\u003eNetwork map of journals that were cocited based on Vosviewer. \u003cstrong\u003e(D) \u003c/strong\u003eTop 20 cited journals with the strongest citation bursts of publications.\u003c/p\u003e","description":"","filename":"FigurePage6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/42d1e8b15ae70d6393762170.jpg"},{"id":53649603,"identity":"8e089ede-ac9f-43e0-b660-30022a7411c2","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":6740751,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMapping of references in studies on EVs for cartilage regeneration from 2013 to 2023. (A) \u003c/strong\u003eNetwork map of reference analysis based on Vosviewer. \u003cstrong\u003e(B)\u003c/strong\u003e Cluster map ofreference analysis based on CiteSpace. \u003cstrong\u003e(C) \u003c/strong\u003eTop 20 references with the strongest citation bursts of publications.\u003c/p\u003e","description":"","filename":"FigurePage7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/44009f74cb81926b3d25749b.jpg"},{"id":53649602,"identity":"656236e4-c959-4028-b95d-80d196bfc408","added_by":"auto","created_at":"2024-03-28 14:28:05","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":11225504,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMapping of keywords in studies on EVs for cartilage regeneration from 2013 to 2023. (A) \u003c/strong\u003eNetwork visualization of keywords based on Vosviewer, and the frequency is represented by point size. \u003cstrong\u003e(B) \u003c/strong\u003eDistribution of keywords according to the mean frequency of appearance; keywords in yellow appeared later than those in blue.\u003cstrong\u003e (C) \u003c/strong\u003eKeyword clustering visualization from 2013 to 2023. \u003cstrong\u003e(D)\u003c/strong\u003e Keywordtimeline visualization from 2013 to 2023.\u003c/p\u003e","description":"","filename":"FigurePage8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/c5a09b5cc86d9c67eca97483.jpg"},{"id":54117095,"identity":"faa5df78-c187-412e-9038-78062443d291","added_by":"auto","created_at":"2024-04-04 19:52:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1741042,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4162009/v1/cf863314-31a3-4bf4-9e6d-1ac96cfeac25.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Visualization and Bibliometric Analysis of Extracellular Vesicles in Cartilage Regeneration from 2013 to 2023","fulltext":[{"header":"Introduction","content":"\u003cp\u003eArticular cartilage, a layer of connective tissue covering joint surfaces, predominantly comprises chondrocytes and the extracellular matrix they synthesize. Its distinctive biological functions, including robust mechanical properties, result from the specific orientation arrangement of substances such as type 2 collagen and proteoglycans within the extracellular matrix. Unfortunately, when joint cartilage undergoes damage due to factors such as trauma, inflammation, or autoimmunity, its inherent biological functions are compromised. Cartilage defects can escalate to osteoarthritis, precipitating joint pain, stiffness, restricted mobility, and potential disability, posing significant threats to both individual health and societal productivity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the innate challenge lies in the fact that articular cartilage lacks nerves and blood vessels, rendering its natural repair and regeneration processes exceptionally difficult [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, the quest to achieve effective repair and regeneration of cartilage defects, aiming to restore the biological properties of compromised cartilage to the greatest extent possible, remains a formidable challenge.\u003c/p\u003e \u003cp\u003eCurrently, there remains a notable deficiency in effective treatment modalities for the repair and regeneration of joint cartilage defects. Existing surgical interventions for cartilage defects are not without their limitations. While procedures like debridement and microfracture exhibit the ability to repair damaged articular cartilage to some extent, yielding positive short-term clinical outcomes, prolonged postoperative recovery becomes evident in long-term follow-ups. This is primarily due to the repair of fibrocartilage, characterized by inferior mechanical properties and predominant tissue formation [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Such repair outcomes may result in heightened wear, challenges in bearing joint weight, and inadequate integration with surrounding tissues [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Autologous cartilage grafting, while initially effective, experiences diminishing efficacy with patient age and an increased number of transplants. Furthermore, it is constrained by factors such as the location, size, and irregular shape of cartilage defects [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Allogeneic cartilage grafting introduces considerations related to donor availability and the potential for immune rejection [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although autologous chondrocyte transplantation (ACI) has shown improvements over the aforementioned methods, it extends the treatment timeline due to the necessity for at least two surgeries, imposing a significant physical and psychological burden on patients.\u003c/p\u003e \u003cp\u003eIn prior endeavors in cartilage tissue engineering, challenges were encountered, notably stemming from insufficient seed cells and the heightened risk of allograft immune rejection. Contemporary research is increasingly directing its focus towards the modulation of the microenvironment post-articular cartilage injury. A current prominent area of investigation involves the establishment of a conducive regenerative microenvironment utilizing acellular scaffolds to stimulate the innate regenerative potential. Extracellular vesicles (EVs), minute particles enveloped by cell membranes and discharged by nearly all cell types, have emerged as a central component in this approach. These vesicles function as messengers for intercellular communication, harboring a diverse array of bioactive molecules, including proteins, enzymes, mRNA, small non-coding RNA, DNA fragments, and metabolic products, on their surface and within their interiors. Through targeted interactions with recipient cells, EVs exert significant influence on cellular behaviors such as proliferation, differentiation, and apoptosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent studies have provided insights into the presence of EVs in synovial fluid from individuals with osteoarthritis, originating from diverse synovial fibroblasts and immune cells. These EVs exert a notable influence on the advancement of intra-articular inflammation, degradation of the articular cartilage matrix, and apoptosis of chondrocytes [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In contrast, EVs derived from mesenchymal stem cells (MSCs) exhibit significant immunomodulatory, anti-inflammatory, and anti-aging properties. Investigations have revealed that exosomes obtained from umbilical cord MSCs possess the capacity to enhance the migration and proliferation of bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes. Furthermore, they induce the polarization of macrophages towards the regenerative M2 phenotype. Remarkably, these exosomes contribute to the reversal of chondrocyte aging in osteoarthritis (OA) and the restoration of their vitality. This, in turn, facilitates the establishment of a regenerative microenvironment conducive to cartilage repair [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the past decade, the field of EVs therapy for cartilage repair has witnessed substantial advancements. The combination of various EV types with biomaterials has shown immense potential, emerging as a prominent research focus. Despite this progress, a comprehensive analysis and understanding of publication trends in this area are still lacking. Therefore, it is imperative to conduct an exploration and analysis of the trends in this field to guide future research directions.\u003c/p\u003e \u003cp\u003eBibliometric analysis, employing mathematical and statistical methods to scrutinize publications, offers valuable insights into the developmental history, research focal points, and future trajectories of a specific field. By leveraging visual network tools such as CiteSpace, the R package \"bibliometrix,\" and VOSviewer, researchers can obtain a comprehensive understanding of publication conditions, predict research trends, and identify hotspots.\u003c/p\u003e \u003cp\u003eThis study performs a novel bibliometric analysis using visual network tools to bridge the knowledge gap and fulfill research needs in the field of EV therapy for cartilage regeneration. The analysis comprehensively examines the literature related to EV therapy for cartilage regeneration from 2013 to 2023, visualizing the developmental trends. It stands as the first scientific and comprehensive analysis of research related to EV therapy for cartilage regeneration, offering insights into the research direction in this field.\u003c/p\u003e \u003cp\u003eThe significance of this study lies in its addressal of the lack of comprehensive analysis in the field, providing valuable information for researchers. It aids researchers in understanding the current status and hotspots in EV therapy for cartilage regeneration, steering them away from unnecessary detours and enhancing research efficiency. Furthermore, this study guides researchers in formulating reasonable goals and finding suitable research directions. By aggregating big data in the field, this study promotes the sharing of information resources and bolsters researchers' comprehensive capabilities.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source and search strategy\u003c/h2\u003e \u003cp\u003eRecognized as one of the most comprehensive and authoritative databases, the Web of Science Core Collection (WoSCC) boasts over 12,000 international academic journals. Hence, it was selected as the primary source to gather global scholarly information for bibliometric analysis, building on previous publications. In this study, we utilized WoSCC to acquire worldwide data for bibliometric analysis. All published articles were systematically retrieved from WoSCC, covering the period from October 1, 2013, to October 1, 2023, with the search conducted on October 4, 2023. Employing the advanced search section function, the search terms were as follows (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) Theme\u0026thinsp;=\u0026thinsp;Extracellular vesicle or Exosome or Microvesicle or Ectosome or Apoptotic body or Apoptotic bleb or Oncosome AND Theme\u0026thinsp;=\u0026thinsp;Cartilage regeneration or Cartilage repair AND Published year = (2013.10.01\u0026ndash;2023.10.01). The exclusion criteria applied in this study were as follows: [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Papers that were not categorized as articles or reviews were excluded, and (2) papers not written in English were also excluded.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection and statistics\u003c/h2\u003e \u003cp\u003eWe meticulously recorded details of all publications, encompassing nationality, journal name, title, year of publication, author's name, affiliation, funding agency, and research direction. The data was stored in a downloadable format and subsequently imported into Excel 2021 for further analysis. The co-authors independently conducted the search and extraction of data from these studies. Any discrepancies were addressed through consultation with experts, resulting in a final consensus. Subsequently, all data was thoroughly cleansed and analyzed individually by co-authors using GraphPad Prism and Origin 2021.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eBibliometric analysis and visualization\u003c/h2\u003e \u003cp\u003eIn our analysis, the number of publications and their citations were directly obtained from WoSCC, and we calculated the relative research interest (RRI) to reflect the ratio of publications in the specific research area each year to the total number of publications in that year. The publishing years were considered from 2013 to 2023, and GraphPad Prism8 was utilized for data analysis. To visualize the global distribution of publications, we utilized R software, including scipy, matplotlib, numpy, and Python, to generate a world map.\u003c/p\u003e \u003cp\u003eFor an in-depth examination of the total publications from leading countries, we accessed and analyzed data using WoS and GraphPad Prism8. The H-index, serving as a measure of research impact, was analyzed for scholars by GraphPad Prism8.\u003c/p\u003e \u003cp\u003eTo explore the networks within the literature, VOS viewer was employed to construct literature networks, and analyses of co-citation, co-occurrence, and couple of bibliography were conducted using this software. Visualization of publications and their corresponding relationships between countries was accomplished using R language.\u003c/p\u003e \u003cp\u003eFor a comprehensive overview of journals, strong citation bursts of keywords and references, and cluster analysis of co-citation of keywords, CiteSpace (6.1.R2) was employed to generate summaries.\u003c/p\u003e \u003cp\u003eIn summary, a diverse set of software tools, including GraphPad Prism8, VOS viewer, R software, and CiteSpace, were utilized to conduct a comprehensive bibliometric analysis, ensuring a thorough exploration of publications, citations, and networks in the field of interest.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eOverall performance of global literature\u003c/h2\u003e\n \u003cp\u003eIn accordance with the specified search criteria, a total of 308 studies were initially collected and analyzed spanning the years 2013 to 2023. Following the exclusion of editorial material (4), meeting abstracts (3), and one non-English study, a refined dataset of 300 studies was identified. As depicted in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA, the global literature on this subject exhibited continuous growth from 2013 to 2023, with a particularly pronounced surge in the last 5 years, indicating a rapid upward trajectory. The total number of global studies escalated from 1 in 2013 to 89 in 2022. Notably, the peak year for study publications in the past decade was 2017 (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). The escalating trend in published literature aligns with an evident increase in research interest in this field over the years (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e\n \u003cp\u003eVOSviewer analysis revealed contributions from 50 countries/regions in this field. As illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC, China emerged as the leading contributor with 161 papers, followed by the USA (36), Italy (20), England (14), and South Korea (14). China accounted for nearly 55% of the total publications among the top 10 countries/regions, with the combined output of the second and third countries, the USA and Italy, amounting to only 22.4% and 12.4% of China\u0026apos;s total, respectively. Notably, China has consistently led in publications annually since 2017, underscoring its pivotal role as the primary driving force in advancing this field.\u003c/p\u003e\n \u003cp\u003eIn summary, the research on exosome-related cartilage regeneration has garnered increasing attention globally, marking a phase of rapid development and growth.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eDistribution of publications in countries\u003c/h2\u003e\n \u003cp\u003eAs depicted in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA, publications with the highest total citation frequencies originated from China (4403), followed by Singapore (1733), the USA (1108), the Netherlands (608), and Iran (448). In terms of relative publications and the H-index, China (35) played a dominant role in this field, followed by the USA (18), Italy (12), Iran (10), and South Korea (9) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC). Notably, publications from Singapore exhibited the highest average citation frequencies (144.4), followed by the Netherlands (50.6), Iran (34.4), England (30.8), and the USA (30.7) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of country/regional collaboration\u003c/h2\u003e\n \u003cp\u003eThe authorship-country collaboration analysis, conducted via VOSviewer (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eC), highlighted the United States as the most intensively collaborating nation, boasting a total link strength of 51. This indicates that the USA has the strongest international collaboration in the field. In contrast, despite having the highest research output, China exhibited a considerably lower total link strength of 25, suggesting that the majority of China\u0026apos;s research endeavors have been focused on domestic collaboration. In essence, the USA and China hold prominent positions in international cooperation, with other countries also engaging in collaboration, albeit to a lesser extent and often not as closely interconnected as their collaborations with the United States and China.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of institutions\u003c/h2\u003e\n \u003cp\u003eIn terms of publication ranking, Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e lists the top 10 contributing institutions, with Shanghai Jiao Tong University being the leading contributor in terms of the number of articles. When examining international collaboration between institutions, the top institution was Future Biol (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eD). Interestingly, institutions from China accumulated the highest number of citations, yet none of them ranked prominently in the collaboration rankings. This suggests that Chinese institutions demonstrated a stronger inclination towards domestic cooperation, consistent with the analysis of country collaboration. Utilizing VOSviewer (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eB), the impact of each research was estimated based on citations, considering the citations in the top 20 institutions. In this context, Sichuan University emerged as the institution with the highest impact (link strength 18985), followed by Shanghai Jiao Tong University (link strength 16698), and the National University of Singapore (link strength 13467). Notably, Sichuan University, despite not having the highest research output, demonstrated a relatively strong research impact.\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 10 institutions published literature related to EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInstitution\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eArticle counts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShanghai Jiao Tong University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSichuan University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNational University of Singapore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingapore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTongji University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChinese People S Liberation Army General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNanjing Medical University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhejiang University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIrccs Istituto Ortopedico Galeazzi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeking University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSun Yat Sen University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 10 well-represented research areas.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eResearch Areas\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRecords\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCell Biology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaterials Science\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResearch Experimental Medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiotechnology Applied Microbiology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScience Technology Other Topics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiochemistry Molecular Biology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEngineering\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePharmacology Pharmacy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrthopedics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 10 funds related to EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eJournal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eArticle counts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNational Natural Science Foundation of China Nsfc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNational Institutes of Health Nih Usa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnited States Department Of Health Human Services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUk Research Innovation Ukri\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina Postdoctoral Science Foundation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNational Key R D Program of China\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedical Research Council Uk Mrc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeijing Natural Science Foundation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean Union Eu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMinistry of Health Italy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of authors\u003c/h2\u003e\n \u003cp\u003eIn total, 152 authors in the field, each having published more than 2 articles, were considered and analyzed using VOSviewer. The collaboration analysis assessed the relatedness of authors based on the number of articles they co-authored. The top 5 authors with the most publications EVs for cartilage regeneration were Toh, Wei Seong; Ragni, Enrico; De Girolamo, LAURA; Lim, Sai Kiang; and Orfei, Carlotta Perucca (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). Toh, Wei Seong, in particular, published 9 articles with 1144 citations, indicating a significant contribution and leading role in the field from both publication and citation perspectives. The visualization of author collaboration in VOSviewer (Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eB) revealed the existence of two collaboration circles of researchers. Bibliographic coupling analysis and co-citation analysis of authors are presented in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eA and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eC, respectively. The link strength between two authors signifies the correlation of their research fields. The results indicate that Zhang, SP, and Toh, Wei Seong, are the authors with the highest link strength, indicating that their research findings are widely recognized in the field.\u003c/p\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 10 most productive journals related to EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eJournal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003eArticle counts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eImpact factor (IF, 2022)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eFrontiers in Bioengineering and Biotechnology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eFrontiers in Cell and Developmental Biology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eInternational Journal of Molecular Sciences\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eStem Cell Research Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eCells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eJournal of Nanobiotechnology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eStem Cells International\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eBiomedicines\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eCartilage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.3313%;\"\u003e\n \u003cp\u003eJournal of Orthopaedic Translation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 14.2443%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 10 authors with the most publications on EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHighly Published Authors\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eArticle counts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003epercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eToh, Wei Seong\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRagni, Enrico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDe Girolamo, LAURA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLim, Sai Kiang\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrfei, Carlotta Perucca\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHui, James Hoi Po\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLai, Ruenn Chai\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang, Shipin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eColombini, Alessandra\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYin, Feng\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eCitation burst, reflecting the references of interest to researchers in a specific period, is also an important indicator. In our analysis, the top strongest citation bursts were identified. Specifically, CiteSpace summarized a total of 20 publications, presented in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eD. The study by Zhang S maintained the strongest citation burst with a strength of 9.69, lasting from 2017 to 2019.\u003c/p\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of research areas and journals\u003c/h2\u003e\n \u003cp\u003eThe 10 most productive journals in this study are presented in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. Frontiers in Bioengineering and Biotechnology emerged as the leading journal, publishing 17 articles. Other notable journals include Frontiers in Cell and Developmental Biology (12 publications), International Journal of Molecular Sciences (11 publications), Stem Cell Research Therapy (11 publications), and Cells (9 publications). In terms of co-citation analysis using VOSviewer, journals with fewer than 10 citations were excluded. As visualized in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, a total of 251 journals were analyzed for total link strength. The top 5 journals with the highest total link strength were Stem Cell Research Therapy (total citations\u0026thinsp;=\u0026thinsp;1080), Biomaterials (total citations\u0026thinsp;=\u0026thinsp;841), Osteoarthritis and Cartilage (total citations\u0026thinsp;=\u0026thinsp;811), SCI REP-UK (total citations\u0026thinsp;=\u0026thinsp;554), and J Extracell Vesicles (total citations\u0026thinsp;=\u0026thinsp;572), as detailed in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eA summary of research orientations, generated using VOSviewer, is presented in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The most prevalent research fields include Cell Biology, Materials Science, Experimental Medicine, Biotechnology, and Applied Microbiology, as well as Science Technology Other Topics. These research orientations provide insights into the current focus and potential areas of development in the field.\u003c/p\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of references and funds\u003c/h2\u003e\n \u003cp\u003eTo identify the most influential literature, co-citation references were analyzed using VOSviewer (Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eA). The article by Tao Sc had the highest link strength. The references were clustered into four main groups: mesenchymal stem cell, critical-sized, exosome, and bone regeneration (Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eB). Additionally, the top 5 research articles with the most citations in the field of EVs for cartilage regeneration are shown in Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e. The article titled \u0026quot;MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis, and modulating immune reactivity\u0026quot; was the most cited research article, with 509 citations. The article titled \u0026quot;MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment\u0026quot; was the most cited review article, with 295 citations. Furthermore, Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eC provides more details on related articles, including the citation burst for each reference. The paper by Zhou Y, published in 2013, had the strongest citation burst, lasting from 2015 to 2017.\u003c/p\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 5 research articles with the most citations in the field of EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTitle\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFirst author\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eJournal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIF\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePublication year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal citations\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang, SP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiomaterials\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e509\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExosomes derived from human embryonic mesenchymal stem cells promote osteochondral\u0026nbsp;regeneration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang, S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteoarthritis and Cartilage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e419\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntegration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLiu, XL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNanoscale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang, SP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiomaterials\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e275\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMao, GP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStem Cell Research \u0026amp; Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe top 5 review articles with the most citations in the field of EVs for cartilage regeneration from 2013 to 2023.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTitle\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFirst author\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eJournal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIF\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePublication year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal citations\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eToh, WS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeminars in Cell \u0026amp; Developmental Biology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e295\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtracellular vesicles, exosomes and shedding vesicles in regenerative medicine - a new paradigm for tissue repair\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBjorge, IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiomaterials Science\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e177\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMianehsaz, E\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStem Cell Research \u0026amp; Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCartilage repair by mesenchymal stem cells: Clinical trial update and perspectives\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLee, WYW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJournal of Orthopaedic Translation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMacrophages: The Good, the Bad, and the Gluttony\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRoss, ERA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrontiers in Immunology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eA list of funding sources for EVs in cartilage regeneration is summarized in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. According to the table, the National Natural Science Foundation of China supported the highest number of articles (100 articles), followed by the National Institutes of Health (15 articles) and the United States Department of Health and Human Services (15 articles). Interestingly, the top three funding sources supporting the most articles are from China and the United States, consistent with previous analyses of countries..\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eAnalysis of keywords and hotspots\u003c/h2\u003e\n \u003cp\u003eUsing VOSviewer\u0026apos;s algorithm, the burst of keywords based on burst detection was analyzed and visualized. The co-occurrence analysis of keywords is displayed in Fig. \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003eA and \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003eB, with the keyword \u0026quot;osteoarthritis\u0026quot; having the highest link strength, indicating a significant focus on EVs therapies in osteoarthritis. The keywords were primarily grouped into nine categories and arranged in a timeline. Notably, \u0026quot;mesenchymal stem cells\u0026quot; has been a topic of interest for researchers for many years, indicating that EVs derived from MSCs are hotspots in cartilage regeneration. Furthermore, keywords such as \u0026quot;osteochondral repair,\u0026quot; \u0026quot;runx2,\u0026quot; and \u0026quot;drug delivery\u0026quot; have also frequently appeared during the period of 2013\u0026ndash;2023. This suggests ongoing research interest and emphasis on these specific aspects in the field of EV therapies for cartilage regeneration.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOver the past decade, substantial efforts have been dedicated to exploring the application of extracellular vesicles for cartilage repair and regeneration. This study contributes a comprehensive bibliometric and visualization analysis covering the period from 2013 to 2023. The utilization of bibliometric software has become increasingly prevalent, offering a valuable tool for researchers. Bibliometric analysis facilitates an intuitive and systematic understanding of the development process and trends within a specific field. Moreover, it aids in the identification of emerging research hotspots and achievements, providing valuable insights for both novices and seasoned researchers alike.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eTrends of global development of EVs for cartilage repair and regeneration\u003c/h2\u003e \u003cp\u003eAs evident from the visualized figures, there is a notable upward trend in the number of publications from October 1, 2013, to October 1, 2023. Concurrently, the relative research interest has also seen a surge in recent years, indicating a growing popularity in this field.\u003c/p\u003e \u003cp\u003eRegarding national contributions, China has emerged as the leader with over 100 publications, making it the highest contributor over the past decade, followed by the United States and Italy. China also leads in terms of the total number of citations and the highest H-index of related publications. However, when considering average citations, Singapore surpasses all other countries, with China ranking sixth. These findings suggest that while China has a significant influence in this field and produces high-quality research, there is room for improvement in the average quality of academic publications. Eight of the top 10 institutions in terms of the number of publications are from China, and four of the top 10 funding sources in the field are also from China, with the first place belonging to China. This highlights the close relationship between China's high academic influence globally and the support from research platforms and funds. Furthermore, the backing of research platforms and funding serves as the foundation for conducting impactful research. As the field continues to advance, collaboration among nations, institutions, and researchers is expected to intensify, catalyzing further breakthroughs and innovations in the application of EVs for cartilage repair and regeneration. This global trajectory promises a future where EV-based therapies play a pivotal role in enhancing the clinical outcomes of individuals grappling with cartilage-related disorders.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eStatus of authors and studies\u003c/h2\u003e \u003cp\u003eIn contrast to the country-based publication trends, authors from Singapore emerge as prominent contributors with the highest individual article count and the highest representation in the top 10 prolific authors, surpassing even their Italian counterparts. Moreover, Singaporean authors exhibit notable collaboration and are cited most frequently in related publications, indicating a focused and advanced exploration of EVs applications in cartilage defect repair and regeneration within the scholarly community of Singapore. In-depth investigations by Italian researchers are also evident. Conversely, China would benefit from an increased concentration of researchers specializing in this domain.\u003c/p\u003e \u003cp\u003eExamining specific publications, the most cited primary authors in both review and research literature are Singaporean scholars, Zhang, SP, and Toh, WS, respectively. Their research findings, notably Zhang's accomplishment in achieving osteochondral regeneration using exosomes derived from bone marrow mesenchymal stem cells, have garnered widespread recognition [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This study demonstrates that exosomal CD73 facilitates cell migration and proliferation by activating the AKT and ERK signaling pathways. Furthermore, exosome-treated cartilage defects exhibit a regenerative immunophenotype characterized by high M2 macrophage infiltration and low IL-1b and TNF-a expression.\u003c/p\u003e \u003cp\u003eBeyond author analysis, this study delves into the prevailing research landscape based on published journals. Noteworthy publications in this field predominantly appear in journals such as Frontiers in Bioengineering and Biotechnology, Frontiers in Cell and Developmental Biology, and the International Journal of Molecular Sciences. The listed journals in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e provide insights into current research hotspots and directions. Additionally, journal-based citation analysis identifies Stem Cell Research \u0026amp; Therapy (IF\u0026thinsp;=\u0026thinsp;7.5) as the most cited journal, signifying its significant contribution to the field.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of research hotspots\u003c/h2\u003e \u003cp\u003eThe research trends and frontiers in EVs for cartilage defect repair and regeneration are elucidated through keyword analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003eA and B highlight \"Osteoarthritis\" as the keyword with the highest frequency in publications, indicating that the primary focus of current research lies in understanding the role and therapeutic potential of EVs in osteoarthritis [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA visual analysis of keyword clustering identifies nine main research clusters, shedding light on promising hotspots in the field. These clusters likely represent distinct areas of investigation and innovation within the application of EVs for cartilage repair and regeneration.\u003c/p\u003e \u003cp\u003eMSCs stand out as a significant research cluster, emphasizing the pluripotent nature of these stem cells and their ability to release bioregulatory nucleic acids and proteins via EVs [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This suggests a growing interest in utilizing EV-based therapies as an alternative to traditional stem cell approaches for cartilage repair [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven that extracellular vesicles essentially comprise cell-derived biological membranes, facilitating substance exchange between cells and participating in diverse physiological and pathological processes [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], their free entry and exit properties could be harnessed for efficient drug delivery, thereby enhancing drug action efficacy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. EVs present opportunities to regulate various stages of pathological changes after cartilage injury. By understanding and manipulating the content of EVs, researchers aim to achieve precise and targeted regulation, potentially influencing signaling pathways like Wnt and AKT [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The immunomodulatory functions of EVs, particularly in the regulation of macrophage polarization and the transformation of dendritic cells and Treg cells, are garnering attention [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This suggests a focus on understanding the immune response and its modulation for effective cartilage regeneration. Future studies are anticipated to delve deeper into the mechanisms through which EVs contribute to cartilage defect repair [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. This reflects a desire for a comprehensive understanding of the cellular and molecular processes involved, enabling more precise interventions.\u003c/p\u003e \u003cp\u003eIn summary, the research hotspots in the field of EVs for cartilage defect repair and regeneration encompass osteoarthritis, MSCs, biological membranes, drug delivery, regulation of pathological changes, immunomodulation, and the exploration of underlying mechanisms. These trends highlight the multidimensional approach researchers are taking to harness the therapeutic potential of EVs in addressing cartilage injuries.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eProspects for EVs in cartilage regeneration\u003c/h2\u003e \u003cp\u003eArticular cartilage presents challenges in repair post-defect due to its absence of structural features like blood vessels and nerves. The excessive inflammatory response post-cartilage defect triggers various degrading enzymes, including MMPs, ADAMTS, leading to increased catabolism of the cartilage matrix. EVs have emerged as promising players in the realm of cartilage regeneration, offering novel therapeutic avenues for addressing the challenges associated with cartilage defects and osteoarthritis. Deepening the application of extracellular vesicles to regulate different stages of pathological changes after cartilage injury offers a pathway for cartilage defect repair and regeneration. As we delve into the prospects for EVs in cartilage regeneration, it becomes evident that these nanosized vesicles hold immense potential for revolutionizing the field of regenerative medicine.\u003c/p\u003e \u003cp\u003eOne of the key prospects lies in the regenerative capabilities inherent in EVs derived from various cell sources, particularly MSCs. MSC-derived EVs have been shown to carry a cargo of bioactive molecules, including proteins, nucleic acids, and microRNAs, capable of modulating cellular activities crucial for cartilage repair [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The paracrine effects mediated by MSC-derived EVs play a pivotal role in promoting cell proliferation, attenuating apoptosis, and orchestrating anti-inflammatory responses within the damaged cartilage microenvironment.\u003c/p\u003e \u003cp\u003eMoreover, EVs present a unique advantage in terms of their natural composition, mimicking the cell membrane and facilitating biocompatibility. This characteristic makes EVs an attractive alternative to traditional cell-based therapies, offering a cell-free approach to cartilage regeneration [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The capacity of EVs to traverse biological barriers, including the blood-brain barrier, enhances their therapeutic potential, allowing for targeted and minimally invasive interventions.\u003c/p\u003e \u003cp\u003eThe versatility of EVs extends to their immunomodulatory properties, influencing the behavior of immune cells involved in the inflammatory response associated with cartilage injuries. By promoting the polarization of macrophages toward anti-inflammatory phenotypes and regulating immune cell activities, EVs contribute to the creation of a favorable microenvironment for cartilage regeneration. Moreover, exosomes derived from mesenchymal stem cells contain a variety of miRNAs and proteins with immunomodulatory functions, regulating macrophage polarization to the M2 phenotype and promoting the transformation of tolerant dendritic cells and Treg cells [\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, ongoing research is unraveling the potential of engineered EVs, designed to carry specific therapeutic payloads [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. These designer EVs can be tailored to enhance their regenerative capabilities, delivering targeted growth factors, signaling molecules, or gene therapies directly to the site of cartilage damage [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. This opens new avenues for precision medicine in cartilage regeneration, allowing for customized therapeutic interventions based on the unique characteristics of each patient's condition.\u003c/p\u003e \u003cp\u003eDespite the optimistic prospects, challenges remain, such as standardizing isolation techniques, understanding the optimal dosage and timing of EV administration, and ensuring long-term efficacy. Additionally, regulatory frameworks must evolve to accommodate the unique nature of EV-based therapies. Collaborative efforts between researchers, clinicians, and regulatory bodies are essential to navigate these challenges and translate the prospects of EVs in cartilage regeneration from the laboratory to clinical practice. Future studies can explore the mechanisms of extracellular vesicles in cartilage defect repair for precise and targeted regulation.\u003c/p\u003e \u003cp\u003eIn conclusion, the prospects for EVs in cartilage regeneration are marked by their regenerative, biocompatible, and immunomodulatory properties. As research advances, harnessing the full potential of EVs holds the key to unlocking innovative and effective therapies for cartilage defects, providing hope for millions of individuals suffering from osteoarthritis and related conditions. The journey from discovery to clinical application represents a paradigm shift in regenerative medicine, with EVs poised to reshape the landscape of cartilage regeneration in the years to come.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThrough a comprehensive analysis of 300 publications, this bibliometric study provides a detailed overview of exosome-related research in cartilage damage repair and regeneration from 2013 to 2023. The findings contribute to the construction of a knowledge map, illustrating the evolving landscape in this domain. Identifying current trends and potential hotspots, this study offers valuable insights for future researchers in the field.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADAMTS, A disintegrin and metalloproteinase with thrombospondin; BMSCs, bone marrow-derived mesenchymal stem cells; ACI, autologous chondrocyte transplantation; EVs, extracellular vesicles; MMPs, matrix metalloproteinases; MSCs, mesenchymal stem cells; OA, osteoarthritis; RRI, relative research interest; WoSCC, Web of Science Core Collection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe authors declare there are no needs to get ethics approval and consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e The authors declare there are no needs to get ethics approval and consent to participate in this study. Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e Not acceptable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e \u003cstrong\u003eAuthors' agreement:\u003c/strong\u003e Shicheng Jia designed the project, determined search formula, performed the experiments, and corrected the draft. Tianze Gao and Ruiyang Zhang wrote the paper draft, analyzed, and visualized data. Jiayou ChenandRongji Liang managed the publications, drew the tables and figures. Yuxiang Ren and Xiaocheng Jiang supervised the experimentations. Jianjing Lin provided financial support and ensured the final manuscript. All authors have read and approved the final version of the manuscript. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was funded by Shenzhen“San-Ming” Project of Medicine (No. SZSM202211019), Guangdong Basic and Applied Basic Research Foundation (2022A1515220056) and Shenzhen Science and Technology Innovation Committee Foundation (JCYJ20220530160212028).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of competing interests:\u003c/strong\u003e The authors declare that they have no financial competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eNo acknowledgement.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eX. Tang, S. Wang, S. Zhan, J. Niu, K. Tao, Y. Zhang, J. Lin, The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study, Arthritis Rheumatol, 68 (2016) 648-653.\u003c/li\u003e\n\u003cli\u003eJ. Martel-Pelletier, A.J. Barr, F.M. Cicuttini, P.G. Conaghan, C. Cooper, M.B. Goldring, S.R. Goldring, G. Jones, A.J. Teichtahl, J.-P. Pelletier, Osteoarthritis, Nature Reviews Disease Primers, 2 (2016) 16072.\u003c/li\u003e\n\u003cli\u003eA.J. Sophia Fox, A. Bedi, S.A. Rodeo, The Basic Science of Articular Cartilage: Structure, Composition, and Function, Sports Health: A Multidisciplinary Approach, 1 (2009) 461-468.\u003c/li\u003e\n\u003cli\u003eL. Zhou, V.O. Gjvm, J. Malda, M.J. Stoddart, Y. Lai, R.G. Richards, K. Ki-Wai Ho, L. Qin, Innovative Tissue-Engineered Strategies for Osteochondral Defect Repai r and Regeneration: Current Progress and Challenges, Advanced healthcare materials, (2020).\u003c/li\u003e\n\u003cli\u003eC. Lesage, M. Lafont, P. Guihard, P. Weiss, J. Guicheux, V. Delplace, Material‐Assisted Strategies for Osteochondral Defect Repair, Advanced Science, 9 (2022) 2200050.\u003c/li\u003e\n\u003cli\u003eD. Sun, X. Liu, L. Xu, Y. Meng, H. Kang, Z. Li, Advances in the Treatment of Partial-Thickness Cartilage Defect, International Journal of Nanomedicine, Volume 17 (2022) 6275-6287.\u003c/li\u003e\n\u003cli\u003eC.L. Camp, M.J. Stuart, A.J. Krych, Current Concepts of Articular Cartilage Restoration Techniques in the Knee, Sports Health: A Multidisciplinary Approach, 6 (2013) 265-273.\u003c/li\u003e\n\u003cli\u003eR.S. Tuan, A.F. Chen, B.A. Klatt, Cartilage Regeneration, J. Am. Acad. Orthop. Surg., 21 (2013) 303-311.\u003c/li\u003e\n\u003cli\u003eG. Filardo, L. Andriolo, F. Soler, M. Berruto, P. Ferrua, P. Verdonk, F. Rongieras, D.C. Crawford, Treatment of unstable knee osteochondritis dissecans in the young adul t: results and limitations of surgical strategies-The advantages of al lografts to address an osteochondral challenge, Knee surgery, sports traumatology, arthroscopy : official journal of t he ESSKA, 27 (2018) 1726-1738.\u003c/li\u003e\n\u003cli\u003eS. Imade, N. Kumahashi, S. Kuwata, J. Iwasa, Y. Uchio, Effectiveness and limitations of autologous osteochondral grafting for the treatment of articular cartilage defects in the knee, Knee surgery, sports traumatology, arthroscopy : official journal of t he ESSKA, 20 (2011) 160-165.\u003c/li\u003e\n\u003cli\u003eJ. Malda, J. Boere, C.H.A. van de Lest, P.R. van Weeren, M.H.M. Wauben, Extracellular vesicles \u0026mdash; new tool for joint repair and regeneration, Nature Reviews Rheumatology, 12 (2016) 243-249.\u003c/li\u003e\n\u003cli\u003eR.J. Berckmans, R. Nieuwland, M.C. Kraan, M.C.L. Schaap, D. Pots, T.J.M. Smeets, A. Sturk, P.P. Tak, Synovial microparticles from arthritic patients modulate chemokine and cytokine release by synoviocytes, Arthritis Research \u0026amp; Therapy, 7 (2005) R536-R544.\u003c/li\u003e\n\u003cli\u003eT. Kato1, S. Miyaki, H. Ishitobi, Y. Nakamura1, T. Nakasa1, M.K. Lotz, M. Ochi, Exosomes from IL-1\u0026beta; stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes., Arthritis Research \u0026amp; Therapy 16 (2014) R163.\u003c/li\u003e\n\u003cli\u003eJ.r.H.W. Distler, A.J. ngel, L.C. Huber, C.A. Seemayer, C.F.R. III, R.E. Gay, B.A. Michel, A. Fontana, S. Gay, D.S. Pisetsky, O. Distler, The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles, Proceedings of the National Academy of Sciences of the United States of America, 102 (2005) 2892-2897.\u003c/li\u003e\n\u003cli\u003eH. Cao, M. Chen, X. Cui, Y. Liu, Y. Liu, S. Deng, T. Yuan, Y. Fan, Q. Wang, X. Zhang, Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes, ACS Nano, 17 (2023) 13358-13376.\u003c/li\u003e\n\u003cli\u003eS. Jiang, G. Tian, Z. Yang, X. Gao, F. Wang, J. Li, Z. Tian, B. Huang, F. Wei, X. Sang, L. Shao, J. Zhou, Z. Wang, S. Liu, X. Sui, Q. Guo, W. Guo, X. Li, Enhancement of acellular cartilage matrix scaffold by Wharton\u0026apos;s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration, Bioactive Materials, 6 (2021) 2711-2728.\u003c/li\u003e\n\u003cli\u003eS. Zhang, S.J. Chuah, R.C. Lai, J.H.P. Hui, S.K. Lim, W.S. Toh, MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity, Biomaterials, 156 (2018) 16-27.\u003c/li\u003e\n\u003cli\u003eB. You, C. Zhou, Y. Yang, MSC-EVs alleviate osteoarthritis by regulating microenvironmental cells in the articular cavity and maintaining cartilage matrix homeostasis, Ageing Research Reviews, 85 (2023) 101864.\u003c/li\u003e\n\u003cli\u003eZ. Liu, Y. Zhuang, L. Fang, C. Yuan, X. Wang, K. Lin, Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis, Bioactive Materials, 22 (2023) 423-452.\u003c/li\u003e\n\u003cli\u003eH. Yin, M. Li, G. Tian, Y. Ma, C. Ning, Z. Yan, J. Wu, Q. Ge, X. Sui, S. Liu, J. Zheng, W. Guo, Q. Guo, The role of extracellular vesicles in osteoarthritis treatment via microenvironment regulation, Biomaterials Research, 26 (2022) 52.\u003c/li\u003e\n\u003cli\u003eB. Yin, J. Ni, C.E. Witherel, M. Yang, J.A. Burdick, C. Wen, S.H.D. Wong, Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics, Theranostics, 12 (2022) 207-231.\u003c/li\u003e\n\u003cli\u003eX. Zhao, Y. Zhao, X. Sun, Y. Xing, X. Wang, Q. Yang, Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis, Frontiers in Bioengineering and Biotechnology, 8 (2020) 575057.\u003c/li\u003e\n\u003cli\u003eK. Li, G. Yan, H. Huang, M. Zheng, K. Ma, X. Cui, D. Lu, L. Zheng, B. Zhu, J. Cheng, J. Zhao, Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages, Journal of Nanobiotechnology, 20 (2022) 38.\u003c/li\u003e\n\u003cli\u003eG. Qiu, G. Zheng, M. Ge, J. Wang, R. Huang, Q. Shu, J. Xu, Functional proteins of mesenchymal stem cell-derived extracellular vesicles, Stem Cell. Res. Ther., 10 (2019) 359.\u003c/li\u003e\n\u003cli\u003eC.H. Woo, H.K. Kim, G.Y. Jung, Y.J. Jung, K.S. Lee, Y.E. Yun, J. Han, J. Lee, W.S. Kim, J.S. Choi, S. Yang, J.H. Park, D.G. Jo, Y.W. Cho, Small extracellular vesicles from human adipose‐derived stem cells attenuate cartilage degeneration, Journal of Extracellular Vesicles, 9 (2020) 1735249.\u003c/li\u003e\n\u003cli\u003eS. Li, J. Liu, S. Liu, W. Jiao, X. Wang, Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis, Journal of Nanobiotechnology, 19 (2021) 343.\u003c/li\u003e\n\u003cli\u003eS. Keshtkar, N. Azarpira, M.H. Ghahremani, Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine, Stem Cell. Res. Ther., 9 (2018) 63.\u003c/li\u003e\n\u003cli\u003eG. van Niel, G. D\u0026apos;Angelo, G. Raposo, Shedding light on the cell biology of extracellular vesicles, Nature reviews. Molecular cell biology, 19 (2018) 213-228.\u003c/li\u003e\n\u003cli\u003eP. Vader, E.A. Mol, G. Pasterkamp, R.M. Schiffelers, Extracellular vesicles for drug delivery, Adv. Drug Del. Rev., 106 (2016) 148-156.\u003c/li\u003e\n\u003cli\u003eS. Li, S. St\u0026ouml;ckl, C. Lukas, M. Herrmann, C. Brochhausen, M.A. K\u0026ouml;nig, B. Johnstone, S. Gr\u0026auml;ssel, Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1\u0026beta;-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p, Stem Cell. Res. Ther., 12 (2021) 252.\u003c/li\u003e\n\u003cli\u003eH. Hu, L. Dong, Z. Bu, Y. Shen, J. Luo, H. Zhang, S. Zhao, F. Lv, Z. Liu, miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration, Journal of Extracellular Vesicles, 9 (2020) 1778883.\u003c/li\u003e\n\u003cli\u003eB.L. Thomas, S.E. Eldridge, B. Nosrati, M. Alvarez, A.S. Thorup, G. Nalesso, S. Caxaria, A. Barawi, J.G. Nicholson, M. Perretti, C. Gaston‐Massuet, C. Pitzalis, A. Maloney, A. Moore, R. Jupp, F. Dell\u0026apos;Accio, WNT3A‐loaded exosomes enable cartilage repair, Journal of Extracellular Vesicles, 10 (2021) e12088.\u003c/li\u003e\n\u003cli\u003eP. Lai, J. Weng, L. Guo, X. Chen, X. Du, Novel insights into MSC-EVs therapy for immune diseases, Biomarker Research, 7 (2019).\u003c/li\u003e\n\u003cli\u003eR. Wu, X. Fan, Y. Wang, M. Shen, Y. Zheng, S. Zhao, L. Yang, Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy, Front. Immunol., 13 (2022).\u003c/li\u003e\n\u003cli\u003eE.I. Buzas, The roles of extracellular vesicles in the immune system, Nature Reviews Immunology, 23 (2022) 236-250.\u003c/li\u003e\n\u003cli\u003eY. Sun, J. Zhao, Q. Wu, Y. Zhang, Y. You, W. Jiang, K. Dai, Chondrogenic primed extracellular vesicles activate miR-455/SOX11/FOXO axis for cartilage regeneration and osteoarthritis treatment, npj Regenerative Medicine, 7 (2022) 53.\u003c/li\u003e\n\u003cli\u003eS. Yuan, G. Li, J. Zhang, X. Chen, J. Su, F. Zhou, Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis, Pharmaceutics, 15 (2023) 1814.\u003c/li\u003e\n\u003cli\u003eS. Rani, A.E. Ryan, M.D. Griffin, T. Ritter, Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications, Mol. Ther., 23 (2015) 812-823.\u003c/li\u003e\n\u003cli\u003eC.R. Harrell, N. Jovicic, V. Djonov, N. Arsenijevic, V. Volarevic, Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases, Cells, 8 (2019) 1605-1626.\u003c/li\u003e\n\u003cli\u003eE. Ragni, C. Perucca Orfei, F. Sinigaglia, L. de Girolamo, Joint Tissue Protective and Immune-Modulating miRNA Landscape of Mesenchymal Stromal Cell-Derived Extracellular Vesicles under Different Osteoarthritis-Mimicking Conditions, Pharmaceutics, 14 (2022) 1400.\u003c/li\u003e\n\u003cli\u003eH. Zhou, X. Shen, C. Yan, W. Xiong, Z. Ma, Z. Tan, J. Wang, Y. Li, J. Liu, A. Duan, F. Liu, Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage, Stem Cell. Res. Ther., 13 (2022) 322.\u003c/li\u003e\n\u003cli\u003eJ. R\u0026auml;dler, D. Gupta, A. Zickler, S.E. Andaloussi, Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading, Molecular therapy : the journal of the American Society of Gene Therap y, 31 (2023) 1231-1250.\u003c/li\u003e\n\u003cli\u003eM.J.W. Evers, S.I. van de Wakker, E.M. de Groot, O.G. de Jong, J.J.J. Gitz-Fran\u0026ccedil;ois, C.S. Seinen, J.P.G. Sluijter, R.M. Schiffelers, P. Vader, Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nan oparticles, Advanced healthcare materials, 11 (2022) e2101202.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bibliometric, Cartilage regeneration and repair, Extracellular vesicles, Exosomes, Visualization","lastPublishedDoi":"10.21203/rs.3.rs-4162009/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4162009/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e \u003c/em\u003eThis study aims to elucidate emerging trends, dynamic advancements, and research focal points in exosome-mediated repair and regeneration of cartilage damage over the past decade, employing a visualization approach.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003eA total of 300 research records focusing on the utilization of exosomes in cartilage damage repair and regeneration were systematically gathered from the Web of Science Core Collection (WoSCC) database spanning the years 2013 to 2023. Utilizing R language, VOSviewer, CiteSpace, and GraphpadPrism software, we conducted analyses on the general features, historical progression, literature, and keywords of this research domain. Ultimately, we predicted the research focal points and latest trends in the application of exosomes for cartilage defect repair and regeneration.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e \u003c/em\u003eThe study amassed a total of 300 articles, revealing a steady increase in publications on exosome application in cartilage repair and regeneration over the years. Significantly, contributions from researchers in China, the USA, and Italy have been pivotal in shaping this field. Keywords clustered into nine distinct research subareas, encompassing mesenchymal stem cells (MSCs), osteochondral repair, runx2, drug delivery, mesenchymal stromal cells, unconventional secretion, biological membranes, and regenerative medicine. Notably, keywords such as \"osteochondral repair,\" \"runx2,\" and \"drug delivery\" featured prominently between 2013 and 2023.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e \u003c/em\u003eThrough a comprehensive review of 300 publications, this bibliometric study provides a detailed overview of exosome-related research in cartilage damage repair and regeneration from 2013 to 2023. The findings contribute to the construction of a knowledge map, illustrating the evolving landscape in this domain. Identifying current trends and potential hotspots, this study offers valuable insights for future researchers in the field.\u003c/p\u003e","manuscriptTitle":"Visualization and Bibliometric Analysis of Extracellular Vesicles in Cartilage Regeneration from 2013 to 2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-28 14:28:00","doi":"10.21203/rs.3.rs-4162009/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"018a02ec-5093-4166-819d-e4270e677acd","owner":[],"postedDate":"March 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-10T12:12:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-28 14:28:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4162009","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4162009","identity":"rs-4162009","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}