{"paper_id":"10331745-5249-4dc7-b8f6-b090399dd0f9","body_text":"Topical hemostatic agents play an important role in modern surgical practice. The application of topical hemostatic agents should be considered as an adjunctive measure to primary hemostatic techniques. They are especially beneficial in cases where the efficacy of conventional methods, including suture ligation and electrocautery, is limited by tissue accessibility, fragility, or the diffuse nature of minor capillary bleeding, making their use impractical [ 1 - 3 ].\nAmong the array of hemostatic materials available, polysaccharide-based agents have gained prominence due to their biodegradability, abundance, biocompatibility, and minimal immunogenicity. These materials have evolved alongside clinical demands and technological advancements, expanding their use beyond hemostasis to include applications such as sealants, wound dressings, and drug delivery systems. One of the most widely adopted polysaccharide-derived hemostatic agents is Oxidized Regenerated Cellulose (ORC). ORC is a chemically modified form of cellulose, first developed in 1942 by Yackel et al. and introduced commercially in 1945 [ 4 - 7 ]. It is widely used due to its favorable clinical characteristics like biocompatibility, biodegradability, absorbability, low toxicity, ease of application, and bactericidal properties. Its versatility and efficacy have led to its integration across various surgical disciplines, including general surgery, neurosurgery, head and neck surgery, thoracic surgery, gynecology, and urology. However, certain contraindications must be considered to ensure safe use. These include the presence of active infection without adequate drainage, direct application to major vessels, encasement of nerves (especially in confined bony spaces), hypersensitivity to ORC, and intraoperative complications such as extensive fractures. Additionally, powdered forms should not be used in blood salvage circuits due to the risk of filter contamination. Caution is advised in patients with poorly controlled diabetes, immunosuppression, ongoing chemotherapy, coagulation disorders, severe obesity, and other comorbidities (e.g., renal or hepatic insufficiency) that may increase the risk of complications [ 6 , 8 , 9 ].\nORC is available in various physical forms, standard, knit, fibril, and non-woven, to suit different surgical needs and bleeding intensities [ 5 ]. It offers significant advantages, including low production cost, minimal risk of thrombotic complications, and a low potential for disease transmission. Additionally, it features a long shelf life, further enhancing its practicality for clinical use [ 5 , 8 ].\nDespite its widespread use, emerging studies point to gaps in our understanding of ORC's full clinical potential, side-effect profile, and optimization in complex surgical environments. This scoping review aims to synthesize the current evidence from clinical trials on the efficacy, safety, and adjunctive benefits of ORC across various surgical disciplines [ 10 ].\nORC's mechanism of action\nThe hemostatic efficacy of ORC is driven by both chemical and mechanical actions, which work synergistically to promote rapid clot formation and wound stabilization. The position of the oxidation sites on the cellulose molecule determines the physicochemical properties of ORC, which in turn dictates its efficacy. Through a process of oxidation, hydroxyl groups on the cellulose backbone are converted into carboxyl groups, forming polyuronic acids [ 11 ]. This structural modification imparts both hemostatic and bactericidal properties [ 8 ]. The acidic environment created by ORC not only contributes to its biodegradability but also promotes vasoconstriction, denaturation of blood proteins, restriction of local blood flow, and red blood cell lysis, facilitating clot formation. It also inhibits bacterial growth, making it particularly useful in contaminated surgical fields [ 11 , 12 ].\nFollowing its application over the site that needs hemostasis, ORC acts by two mechanisms. Firstly, it acts as a scaffold, forming a dense absorbent mass upon contact with blood. This temporary hemostatic scaffold provides a mechanical tamponade over the open capillaries and initiates clot development by activating the coagulation cascade [ 11 ]. ORC is often preferred over other hemostatic agents like gelatin foam due to its dual functionality in promoting clotting and inhibiting microbial growth [ 5 ]. Gelatin foam absorption occurs over weeks but is site-dependent, and is contraindicated in infected wounds because it may exacerbate the infection [ 13 ].\nSecondly, the cohesive and adhesive structure of ORC enables better interaction with clotting factors, further supporting thrombus formation [ 14 ]. The large surface area of the cellulose fibers increases the absorption of blood and tissue exudates, thereby facilitating faster clot formation. More importantly, ORC is typically absorbed by the body within seven to 14 days (Figure  1 ) [ 1 ].\nFigure created by the authors on Microsoft Powerpoint (Microsoft Corp., Redmond, WA, US).\n\nMethodology\nA literature search was conducted using the PubMed Central database maintained by the U.S. National Institutes of Health (NIH). The search term “Oxidized Regenerated Cellulose” was used. The search results were filtered to include only the following types of studies: Clinical Trials, Controlled Clinical Trials, and Randomized Controlled Trials. Additionally, to explore the future clinical potential of ORC, a search was performed on  clinicaltrials.gov  database using the term \"oxidized regenerated cellulose\\ORC\\\". This yielded four relevant studies at various stages of completion. However, one of the completed studies was already identified in the PubMed search, resulting in three unique studies being included in the analysis. These were evaluated to identify prospective developments in the use of ORC across different surgical specialties and wound healing scenarios. The search was completed on June 26, 2025.\nStudies were selected for inclusion based on specific criteria. Only studies conducted on human subjects and those reporting on the comparative efficacy or other clinically-relevant outcomes related to the use of ORC were included. Studies were excluded if they did not involve a direct comparison of ORC with another intervention or control group, assessed ORC in combination with other agents (as these could confound the interpretation of ORC’s standalone effects), retracted publications, and non-comparative studies.\nFive independent reviewers screened all titles and abstracts for eligibility. Full texts of potentially relevant articles were assessed in detail. Any disagreements were resolved through discussion and consensus. From each eligible study, data were systematically extracted and organized according to the following categories: author(s) and year of publication, details of the intervention (specifically the use of ORC), comparator information (such as alternative hemostatic agents or control interventions), indication, reported outcomes, key results, and safety findings, including any adverse effects or complications.\nAs this is a scoping review, a formal risk of bias assessment was not performed. Due to the anticipated clinical and methodological heterogeneity of the included studies, a meta-analysis was not feasible. The results are therefore presented as a narrative synthesis.\nThis review explores several key domains related to the use of ORC. Firstly, it examines the comparative effectiveness of ORC in relation to other hemostatic agents or interventions, assessing its relative performance in clinical settings. Secondly, it discusses the side effects and complications associated with the use of ORC, highlighting potential risks and safety concerns. Lastly, it delves into ongoing research and future prospects, focusing on its advancements in clinical applications and material development.\nResults\nA comprehensive literature search in PubMed Central database yielded 725 records. After applying the filters, the number of articles were reduced to 54. These records were then screened for eligibility, based on the inclusion and exclusion criteria. A total of 26 studies were excluded for the following reasons: two did not involve ORC, one was a retracted article, five were not comparative in nature, and 18 used ORC in combination with another agent, making it difficult to isolate the effects of ORC.\nA comprehensive literature search in  clinicaltrials.gov  database yielded four records. Since one of the completed studies was also retrieved in the PubMed search, only three non-duplicative studies were included in the analysis.\nFinally, 31 studies (28 studies from PubMed Central + three studies from  Clinicaltrials.gov ) were deemed suitable for the final review (Figure  2 ).\nThe flowchart was prepared in accordance with the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [ 15 ].\nAcross these studies, ORC was evaluated not only for its hemostatic properties but also for its effects on adhesion prevention, infection control, and postoperative recovery. A detailed summary of these 28 studies (from PubMed Central), including key findings and study characteristics, is presented in Table  1 .\nORC: Oxidized Regenerated Cellulose; PTFE: Polytetrafluoroethylene.\nHemostatic Efficacy and Blood Loss Control\nSeveral studies examined the ability of ORC to control blood loss in various surgical settings. In orthopedic surgery, Li et al. (2023) [ 6 ] reported a statistically significant reduction in both total and hidden blood loss with the use of ORC compared to the control group following unilateral total knee arthroplasty, highlighting the effectiveness of ORC in managing postoperative hemorrhage. Similarly, Wakasa et al. (2024) [ 17 ] showed that ORC powder was as effective as tranexamic acid in reducing blood loss during total hip arthroplasty, suggesting that ORC could serve as an alternative in patients where systemic antifibrinolytics are contraindicated. In thoracic surgery, Shimizu et al. (2019) [ 16 ] reported no statistically significant difference in median intraoperative blood loss between ORC-treated and control patients undergoing Video-Assisted Thoracoscopic Surgery (VATS), though ORC reduced the need for additional hemostatic interventions.\nImpact on Drainage Volume\nThe use of ORC showed mixed results in reducing postoperative drainage. Wang et al. (2015) [ 19 ] demonstrated a significant reduction in drainage volume post-hepatectomy with the application of ORC compared to the control group (406.9 mL vs. 627.0 mL, p<0.028), suggesting its utility in liver surgery where fluid management is critical. However, other trials, such as that by Nam et al. (2022) [ 18 ] in mastectomy patients, did not find significant differences in seroma formation or drainage volume between the ORC and control groups, indicating that ORC’s benefits may be context-specific and dependent on surgical site characteristics and fluid dynamics.\nTime to Hemostasis (TTH)\nThe ability of ORC to rapidly achieve hemostasis has been well documented, although its performance varies across indications and in comparison with other agents. In cases of low-grade bleeding, such as malignant wound oozing, ORC has shown comparable efficacy to other standard agents. Firmino et al. (2024) [ 20 ] reported that ORC and calcium alginate achieved similar TTH, indicating that ORC is effective in managing mild to moderate bleeding in oncology-related wound care. Conversely, in high-pressure bleeding scenarios such as vascular or hepatic surgeries, ORC was associated with longer TTH. Schenk et al. (2003) [ 24 ] demonstrated that fibrinogen-thrombin sealants achieved significantly faster hemostasis compared to ORC in vascular procedures (mean TTH: 56.3 vs. 772.9 seconds). Similarly, Schenk et al. (2002) [ 25 ] and Genyk et al. (2016) [ 26 ] found that fibrin sealant patches outperformed ORC gauze in hepatic resections and vascular anastomosis, providing faster and more reliable control of bleeding. However, modified forms such as neutralized ORC (NORC) appear to offer improved performance. Develle et al. (2020) [ 21 ] found NORC achieved faster hemostasis than conventional ORC, with 100% of patients achieving hemostasis within two minutes, highlighting the potential for material optimization.\nIn the dental setting, Guardieiro et al. (2023) [ 22 ] compared ORC gauze with a chitosan-based dental dressing following tooth extraction. The chitosan group achieved significantly shorter intraoral bleeding times (two minutes vs. five minutes, P=0.001), suggesting that while ORC is effective, chitosan dressings may offer superior hemostatic control in oral surgical procedures.\nRossman et al. (1999) [ 23 ] evaluated hemostatic methods following palatal donor tissue harvesting. Both ORC and absorbable gelatin sponge significantly reduced the TTH compared to standard gauze pressure. However, postoperative bleeding occurred in 40% of both the ORC and gauze groups, while no bleeding was reported in the gelatin sponge group, indicating a superior safety and efficacy profile for the gelatin sponge.\nIn patients with inherited bleeding disorders, Eshghi et al. (2014) [ 27 ] reported that the chitosan-reinforced tampon achieved significantly faster hemostasis compared to the ORC tampon and the TXA-impregnated tampon (P<0.001). These findings demonstrate that ORC provides moderate efficacy in high-risk patients but is less effective than chitosan in managing epistaxis under coagulopathic conditions.\nAdhesion Prevention and Reformation\nEight studies evaluated ORC’s ability to reduce postoperative adhesions. In laparoscopic myomectomy, studies by Mais et al. (1995) [ 28 , 30 ] and Sawad et al. (2000) [ 31 ] showed that patients receiving ORC had significantly higher adhesion-free rates compared to controls. Similarly, Franklin et al. (1995) [ 33 ] reported fewer and less severe ovarian adhesions with ORC treatment as compared to control. Azziz et al. (1993) [ 34 ] and Sekiba et al. (1992) [ 35 ] conducted paired-site studies in which one side of the pelvic cavity was treated with ORC while the other served as a control, showing significant reductions in both adhesion incidence and extent on the ORC-treated side. While some studies (e.g., Haney et al., 1995 [ 29 ]) found expanded polytetrafluoroethylene (PTFE) barriers to be superior in terms of reducing adhesion severity and surface area, ORC remained advantageous due to its absorbability, ease of use, and reduced risk of foreign body reactions. Tinelli et al. (2011) [ 32 ] further demonstrated that ORC significantly reduced adhesion rates compared to the control group in patients undergoing intracapsular myomectomy, with consistent benefits observed across both open and laparoscopic surgical approaches.\nOther Clinical Outcomes\nAlfieri et al. (2011) [ 36 ] demonstrated that ORC reduced microbial contamination in contaminated stoma sites more effectively than iodine-soaked gauze (66% vs. 25% showed no/reduced contamination). Similarly, Lee et al. (2017) [ 39 ] found lower surgical site infection (SSI) rates with hemostasis-purposed ORC versus adhesion-barrier-purposed ORC in post-mastectomy patients (p=0.042), along with shorter operative times (p=0.027).\nIn colorectal surgery, Naito et al. (2017) [ 37 ] found no increase in adverse events with ORC, and adhesive small bowel obstruction occurred only in the control group, suggesting a favorable safety and usability profile.\nFunctional outcomes such as seroma formation, recovery time, and hospital stay were variably impacted. In thyroidectomy, Scerrino et al. (2013) [ 38 ] observed fewer seromas with fibrin patches than with ORC. Testini et al. (2009) [ 41 ] also reported shorter operative and recovery times with collagen-thrombin matrix compared to ORC.\nIn oral and periodontal procedures, ORC was less effective than newer materials. Gatti et al. (2025) [ 40 ] found no significant difference in pain or healing between ORC and leukocyte- and platelet-rich fibrin (L-PRF), though L-PRF was associated with reduced postoperative stress (p<0.05). Alkan et al. (2004) [ 42 ] showed no benefit of ORC compared to the control in preventing postoperative swelling after third molar extraction, suggesting limited effectiveness of ORC in oral surgical procedures involving soft tissue edema.\nTaken together, these clinical trials reflect a growing trend toward expanding the clinical roles of ORC beyond bleeding control, including applications in infection prevention, adhesion reduction, and wound healing optimization. With its broad-spectrum antibacterial activity, biocompatibility, resorbability, and evolving formulations (e.g., powders and gels), ORC remains a promising candidate for future research and therapeutic innovation in both surgical and nonsurgical domains.\nDiscussion\nThis review underscores the versatility and clinical reliability of ORC as a topical hemostatic agent across a wide range of surgical and bleeding scenarios. In a comprehensive review of topical hemostatic agents, ORC was noted to have a moderate hemostatic effect, but excellent handling characteristics. It did not adhere to instruments, conformed well to tissue surfaces, and was fully resorbed within weeks. These properties support its practical advantages in surgery, minimizing both intraoperative disruption and postoperative complications [ 11 ]. In procedures involving mild to moderate bleeding, such as malignant wound care in palliative settings or during dental extractions, ORC appears to provide satisfactory control [ 3 ]. Firmino et al. (2024) [ 20 ] found no significant difference in time to hemostasis between ORC and calcium alginate, suggesting that ORC remains a viable and cost-effective option for low-grade bleeding. In dental applications, Guardieiro et al. (2023) [ 22 ] showed that while chitosan dressings reduced bleeding time more rapidly, ORC still achieved satisfactory hemostasis within minutes, with no associated adverse effects, confirming its continued relevance in oral surgical practice. Moreover, studies such as Rossman et al. (1999) [ 23 ] have shown that ORC significantly improves intraoperative hemostasis compared to conventional gauze pressure, especially in procedures like palatal donor site management. Although gelatin sponges showed slightly better outcomes in preventing postoperative bleeding, ORC remains an effective, resorbable alternative with minimal complications. These findings further emphasize that ORC performs well in soft tissue surgeries where mechanical support and biocompatibility are critical.\nWhile some studies in high-pressure bleeding environments, such as vascular or hepatic surgeries, report faster hemostasis with fibrin-based sealants [ 24 , 26 ], ORC still provides a safe and effective option, particularly in cases where biologic sealants are either contraindicated or cost-prohibitive. Importantly, ORC does not rely on patient coagulation factors or fibrin formation, making it particularly valuable in patients with coagulopathies or anticoagulant use. Develle et al. (2020) [ 21 ] demonstrated that neutralized ORC achieved faster and more consistent hemostasis than conventional ORC, with all patients reaching bleeding control within two minutes. This highlights the potential of modified ORC formulations to further optimize outcomes while retaining its core advantages. While other agents may offer advantages in select high-risk scenarios, the continued refinement of ORC, such as the development of neutralized or composite forms, positions it strongly for expanded clinical use.\nIn addition to the hemostatic properties, ORC also has demonstrated the ability to inhibit the growth of 32 different bacterial strains, including multi-drug resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), and Candida albicans, with inhibition rates ranging from 50-100%. The complete inhibition of PRSP, a major cause of pneumonia and meningitis, is especially noteworthy and highlights ORC’s potential as a preventive barrier against SSIs. In vitro studies further support its activity against both Gram-positive and Gram-negative pathogens, which may reduce postoperative infection rates [ 5 , 43 ].\nIn addition to its hemostatic and antimicrobial benefits, ORC has emerged as an effective adhesion barrier in abdominal and pelvic surgeries. Several studies [ 44 - 46 ] report its efficacy in preventing postoperative adhesions when applied in sheet form to surgical sites. A meta-analysis [ 47 ] found that ORC significantly reduced adhesion incidence, with no reported cases of reoperation for adhesive small bowel obstruction. Mechanistically, ORC converts into a gel within 24 hours and is phagocytosed by macrophages. It supports tissue repair by promoting fibroblast, epithelial, and endothelial cell activity-further enhancing surgical healing.\nOngoing and Future Research\nFour clinical studies involving ORC are currently registered on  clinicaltrials.gov . As one of the completed studies overlapped with the PubMed search results, only three distinct studies were included in the final analysis. The first trial (Kuo et al. [ 48 ]) is a prospective comparison evaluating ORC versus hyaluronic acid in thyroid and parathyroid surgeries. The study focuses on postoperative adhesion formation and patient-reported swallowing difficulties, measured over one year. This research highlights ORC’s potential dual function as both a hemostatic and an anti-adhesion agent-extending its applicability beyond bleeding control to enhancing postoperative recovery.\nA second completed trial (Al-Attar et al. [ 49 ]) assessed the efficacy and safety of a powdered ORC formulation in managing mild to moderate intraoperative bleeding across various surgical specialties, including general, gynecological, urological, and cardiothoracic procedures. Hemostasis success rates at three, five, and 10 minutes were key endpoints, alongside postoperative complications such as thromboembolic events and rebleeding. The trial's broad scope and multicenter design underscore ORC’s versatility and favorable safety profile across diverse clinical contexts.\nThe third study (Stacey [ 50 ]), although primarily focused on topical growth factors and protease inhibitors in chronic wound healing, indirectly informs future directions for ORC use. While ORC was not the main intervention, the study reflects an evolving therapeutic interest in bioactive wound care solutions. This aligns with the emerging role of ORC-based materials with antimicrobial or regenerative enhancements, particularly in treating complex wounds like diabetic foot ulcers and venous leg ulcers.\nORC consistently demonstrated a favorable safety profile, with no significant reported adverse events. Even in high-risk surgical settings (e.g., hepatic resection, vascular surgery, colorectal procedures, neck dissections, and skull base repairs), ORC use was not associated with increased infection, allergic reaction, or delayed wound healing. When adverse outcomes did occur, such as infections, seromas, or hematomas, they were either attributed to surgical technique or patient factors, not to specific to ORC alone. While newer materials and sealants may offer incremental improvements in specific clinical scenarios, ORC continues to stand out for its unique combination of hemostatic efficacy, ease of use, absorbability, broad antimicrobial action, and additional benefits such as adhesion prevention in GI surgeries and promotion of wound healing.\nLimitations\nWhile this review provides a comprehensive assessment of ORC across diverse surgical applications, several limitations warrant consideration. The studies included in this review vary widely in terms of surgical specialty, patient populations, endpoints, and comparators. This heterogeneity limits the ability to draw direct comparisons or conduct meaningful meta-analyses. For example, TTH and drainage volume were measured using different methodologies across studies, reducing consistency in outcome interpretation. Although several RCTs were identified, many studies were small-scale, retrospective, or lacked blinding. This introduces the potential for bias in outcome reporting and underlines the need for larger, rigorously designed clinical trials to confirm the efficacy of ORC, particularly in comparison with newer or more specialized hemostatic agents. Many included studies used a broad range of alternative materials, such as gelatin sponges, fibrin sealants, or chitosan dressings, without consistent controls. This diversity complicates the evaluation of ORC’s relative performance and cost-effectiveness across clinical contexts. Evidence suggests that ORC’s benefits are highly dependent on the surgical setting and type of bleeding. Few studies assessed long-term postoperative outcomes, such as adhesion reformation, chronic infection risk, or delayed wound healing, over extended follow-up periods. Furthermore, real-world data on cost-effectiveness, surgeon preference, and logistical considerations (e.g., ease of storage, waste) are insufficiently addressed in the current literature. While ORC has shown safety in standard adult populations, limited data exist on its use in pediatric patients, individuals with complex coagulopathies, or those undergoing repeat surgeries. These populations require further investigation to validate ORC’s safety and efficacy.\n\nORC has established itself as a clinically valuable and functionally adaptable hemostatic agent across a wide spectrum of surgical disciplines. Its consistent performance in controlling low to moderate bleeding, along with its ease of application, biocompatibility, and rapid absorbability, make it a dependable option in routine and complex surgical procedures. Moreover, ORC’s intrinsic bactericidal properties and low immunogenicity extend its utility beyond hemostasis, particularly in contaminated surgical fields and infection-prone environments.\nWhile certain advanced agents, such as fibrin sealants, chitosan-based dressings, and synthetic adhesion barriers, have demonstrated superior outcomes in specific high-risk or specialized procedures, they often come with higher costs or increased technical demands. ORC, by contrast, offers a balanced profile of efficacy, safety, and cost-effectiveness, which supports its widespread clinical adoption, especially in resource-constrained settings. Nevertheless, additional high-quality studies are essential to enhance the evidence base and enable clinicians to make informed, evidence-based decisions across diverse surgical contexts.","source_license":"CC-BY-4.0","license_restricted":false}