Radiographic and Histomorphometric Analysis of a Xenograft S1-XB for Socket Preservation in Maxillary Posterior Teeth: A Randomized Controlled Clinical Study

Radiographic and Histomorphometric Analysis of a Xenograft S1-XB for Socket Preservation in Maxillary Posterior Teeth: A Randomized Controlled Clinical Study | 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 Radiographic and Histomorphometric Analysis of a Xenograft S1-XB for Socket Preservation in Maxillary Posterior Teeth: A Randomized Controlled Clinical Study Marwan Aboul Makarem, Mohamed Hassan Eid, Merhan Nabih Elmansy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8223707/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 Background Socket preservation aims to minimize post-extraction ridge resorption. This randomized controlled clinical trial evaluated the radiographic and histomorphometric outcomes of a bovine-derived xenograft combined with alginate hydrogel (S1-XB) compared with natural healing. Aim This study investigated the radiographic and histomorphometric outcomes of socket preservation with a bovine-derived xenograft combined with alginate hydrogel (S1-XB) compared to natural healing in maxillary posterior extraction sites. Materials and Methods Sixteen male patients (21–40 years) requiring atraumatic extraction of maxillary posterior teeth were randomly assigned (1:1) to S1-XB grafting (n = 8) or natural healing (n = 8). Cone-beam computed tomography (CBCT) was performed immediately post-extraction and after 4 months to assess bone density, ridge height, and ridge width. Core biopsies harvested at 4 months were analyzed using H&E, Masson's trichrome, and osteopontin immunohistochemistry. The primary outcome was CBCT-based bone density at 4 months. Secondary outcomes included ridge dimensions, bone area, osteoid, intertrabecular tissue, and osteopontin expression. Results All 16 randomized participants completed the study. Bone density was significantly higher in the grafted group compared with controls (748.66 ± 90.19 HU vs. 514.33 ± 177.58 HU; p < 0.001). Histomorphometry showed significantly greater bone area and lower osteoid and intertrabecular tissue in the grafted sockets. Ridge height and width did not differ significantly between groups. No adverse events occurred. Conclusions S1-XB xenograft significantly enhanced bone density and histological bone quality without altering ridge dimensions at 4 months. The material appears effective for socket preservation prior to implant placement. Trial was retrospectively registered on Clinicaltrials.gov , TNR: NCT07250256 , 11/25/2025 Socket preservation Xenograft Bone density Histomorphometry Osteopontin Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction The alveolar process always has resorptive changes as natural consequence to tooth extraction, occurring commonly after tooth removal. This has been significantly more obvious on empty socket buccal aspect where an increased loss of bone volume has been noticed. 1 The process of natural healing is composed of a complex and dynamic series of events. It starts with blood clot formation immediately which serves as a protective barrier that covers the exposed bone and nerve endings in the socket. It also provides a scaffold for the infiltration of granulation tissue. The formation of a stable clot is essential to prevent alveolar osteitis, commonly known as dry socket. Then, the inflammatory phase involves the recruitment of inflammatory cells to the site to combat infection and clear out debris. Proliferative phase fills the socket with granulation tissue rich in collagen, fibroblasts, and capillaries. Bone formation begins at the periphery of the socket and progresses towards the center. This woven bone eventually matures into harder lamellar bone. Maturation and remodeling to achieve the density and architecture of the original bone. 2 ' 3 Socket preservation is a crucial procedure following tooth extraction, aimed at minimizing bone resorption, and maintaining the contour and volume of the alveolar ridge. This is particularly important in areas where future prosthetic replacements or implants are planned. Moreover, it reduces the necessity for extensive ridge augmentation procedures in the future. 4 Several techniques and materials are used in socket preservation to achieve optimal outcomes. Bone graft has great importance in filling the socket post-extraction, supporting new bone formation and preventing the collapse of the socket walls. 5 The earliest recorded use of a bone graft dates back to 1682, during repair of a cranial defect using a graft obtained from the skull of a deceased dog. 6 Since that time, bone grafts and their substitutes have become integral in clinical practice. A bone graft is generally defined as viable tissue was transplanted into a bone defect, to stimulate bone regeneration and healing either alone or in combination with other materials, with the capacity. 7 In comparison, a bone substitute serves the same purpose but does not contain living cells; instead, it is composed of a mineralized bone matrix of either natural or synthetic origin. 8 Allografts are limited by drawbacks such as the risk of donor tissue rejection and potential disease transmission, including HIV and hepatitis. Autografts, while considered the gold standard, are also associated with notable disadvantages, including limited tissue availability, the requirement for a second surgical site, and the resulting donor site pain and morbidity. 9 To overcome these challenges, alternative grafting strategies have been explored to optimize clinical outcomes. Among these, synthetic bone substitutes and xenografts demonstrate distinct advantages in terms of availability and cost-effectiveness. Notably, xenograft-based hydrogels have been successfully utilized in humans for socket preservation following the extraction of impacted mandibular molars. 10 An ideal bone substitute is expected to combine several key properties, including affordability, ease of handling, minimal patient morbidity, low immunogenicity, and angiogenic potential. However, most commercially available products have yet to demonstrate all these characteristics simultaneously. 11 Based on this gap, the present randomized controlled clinical study aimed to assess the radiographic and histomorphometric outcomes of S1-XB xenograft for the preservation of extraction sockets in maxillary posterior teeth, compared with natural healing. We hypothesized that the use of xenograft would lead to significantly improved bone density and superior histological bone quality after four months, without compromising ridge dimensions. This randomized clinical trial adhered to the CONSORT 2010 recommendations for reporting parallel-group randomized trials. 2 Patients and Methods 2.1 Trial Design This study was a parallel-group, two-arm, 1:1 randomized controlled clinical trial. No changes to the trial design, eligibility criteria, or outcome measures were made after trial commencement. 2.2 Ethical Approval and Registration The trial was approved by the Research Ethics Committee of Suez Canal University (No. 547/2022). The study was not prospectively registered; however, the full protocol was approved before participant enrolment and is available from the corresponding author upon reasonable request 2.3 Recruitment Period Participants were recruited between [August–2022] and [December–2022] , and all follow-up procedures were completed by [December–2024] . 2.4 Sample Size: G* Power analysis version 3.1.9.7 was used to perform the calculation of the sample size. Based on the results of a previous study, 12 alpha level = 0.05, beta = 0.2, power = 80% and absolute error or precision (d) = 1.51. The predicted sample size (n) was 16 samples that were divided equally in both groups. Eight samples in each group were in line with a previous study that tested it in similar subjects. 13 The calculation was based on detecting a clinically meaningful difference in bone density (primary outcome) at 4 months. 2.5 Patients Randomization and Allocation: Sequence generation A simple randomization sequence (1:1) was generated using a computer-based randomizer ( www.randomizer.org ). Allocation concealment: Allocation was concealed using sequentially numbered, opaque, sealed envelopes prepared by an independent research coordinator not involved in enrolment or treatment. Implementation: The random sequence was generated by an independent statistician. Participants were enrolled by a research coordinator. The surgeon opened the next sealed envelope to assign the participant to the study or control group. 2.6 Blinding Due to the nature of the intervention, blinding of the surgeon and participants was not feasible. However: Radiographic outcome assessors and Histopathology examiners were fully blinded to group allocation. 2.7 Outcomes Primary outcome: – Bone density (HU) measured by CBCT at baseline and at 4 months. Secondary outcomes: Ridge height and ridge width (CBCT). Histomorphometric measures (H&E and Masson's trichrome): bone area, osteoid tissue, intertrabecular tissue. Osteopontin (OPN) immunoexpression (% area). No outcome changes were made after trial initiation. Sixteen male patients aged 21–40 years requiring extraction of hopeless maxillary posterior teeth, with sites suitable for future implant placement were randomly assigned (1:1) using a web-based randomizer (www.randomizer.org). Study group (n=8) extracted their teeth, and the sockets were grafted using bovine derived xenograft with alginate hydrogel material (hydroxypropyl methylcellulose) using S1-XB (Medpark/Korea). Control group (n=8) extracted their teeth and were allowed to undergo natural healing. Blinding the surgeon was not feasible due to the nature of the intervention. However, both outcome assessors and histological examiners were blinded to group allocation. 2.8 Harms All adverse events and complications were monitored at each visit. No intraoperative or postoperative complications or adverse events occurred in either group. 2.9 Inclusion criteria: · Male patients aged between 21 and 40 years. · Participants in good general health. · Presence of a single extraction site in the maxillary premolar or molar region. · Adequate mesiodistal and interocclusal space to accommodate implant restoration. · Extraction site suitable for subsequent replacement with a dental implant. 2.10 Exclusion criteria: · Female patients. · Current smokers. · Patients receiving chronic medications known to affect bone turnover (e.g., bisphosphonates). · Patients with psychological disorders or uncontrolled systemic conditions. 2.11 Surgical Procedure All extractions performed by the same surgeon under local anesthesia (4% articaine with 1:100,000 epinephrine) using an atraumatic technique, which involved periotomes, luxators, and tooth sectioning when necessary. Following extraction, all sockets were thoroughly curetted and irrigated with sterile saline (Figure 1). In the study group, S1-XB granules were hydrated with 0.5–1 mL of sterile saline to achieve a workable consistency, then gently packed into the socket up to the crestal level and stabilized using 3-0 silk figure-of-eight sutures. In the control group, sockets were left to heal spontaneously without intervention. All patients received standardized postoperative instructions along with a 5-day course of antibiotics: amoxicillin 500 mg three / day (or azithromycin 500 mg once daily in case of allergy) in combination with metronidazole three / day. Analgesia was provided with 500 mg paracetamol up to three times daily as needed. Additionally, chlorhexidine 0.12% mouthrinse was prescribed twice daily, starting 24 hours after surgery and continuing for 7 days. Sutures were removed between 7 and 10 days postoperatively. At 4 months, a full-thickness flap was raised under local anesthesia. Core biopsies were harvested from the planned implant site using a 2–3 mm trephine to a depth of 2 mm without compromising implant stability. 2.16 Radiographic Analysis Cone-beam computed tomography (CBCT) scans (Scanora 3D) were obtained immediately after extraction at baseline and postponed at 4 months postoperatively to evaluate the following parameters: bone density that was measured in Hounsfield units (HU) at the center of the socket, ridge height that was determined by vertical distance from the crestal bone to a fixed reference point and ridge width that was measured at 3 mm apical to the crest. 2.17 Microscopic Analysis Biopsies were fixed in 10% buffered formalin and decalcified in 10% EDTA for one week with regular renewal of the solution daily. Then, the specimen was dehydrated, cleared in xylol, embedded in paraffin and sectioned using a microtome into thin paraffin sections 5 µ thickness. Sections were stained with different stains according to manufacture instructions. Samples were first stained with hematoxylin and eosin (H&E) to demonstrate the general tissue architecture, cellular distribution, and overall structural organization. Subsequently, sections were stained with Masson’s Trichrome (MTC) to allow both qualitative and quantitative assessment of bone trabeculae and osteoid tissue. Osteopontin (OPN) immunohistochemistry was used to assess the percentage of OPN expression area within the surrounding connective tissue. The OPN poly-colonal antibody was purchased from Thermo Fisher Scientific, Catalog # PA1-72061. Images were captured at ×400 magnification using a SOPTOP EX20 microscope with HD camera. ImageJ software was used to quantify area% from five standardized fields per section at oral pathology laboratory, Faculty of Dentistry, Suez Canal University. 2.18 Statistical Analysis Program of SPSS version 26.0 (IBM Corp., Armonk, NY, USA) was used in data analysis that were represented as mean ± standard deviation (SD). Independent samples t-test was used between-group differences, while paired t-test was applied within-group changes over time at p-value <0.05 as statistically significant. All analyses were performed on an intention-to-treat basis, including all randomized participants. 3 Results All 16 randomized participants received the allocated intervention and completed the study. There were no post-randomization exclusions or losses to follow-up. 3.1 Radiographic Assessment Sixteen patients completed the study with no dropouts. Baseline characteristics, including pre-extraction CBCT measurements, were comparable between groups (p > 0.05). Radiographic evaluation revealed greater radiopacity in the study group compared to the un-grafted control group. The mean bone density was 514.33 ± 177.58 HU in the control group and 748.66 ± 90.19 HU in the study group (Table 1 ). The difference between groups was highly statistically significant (T = 3.359; p < 0.001). Changes in the ridge height and width from baseline to 4 months were minimal and showed no statistically significant differences between groups (T = 0.267; p = 0.793 and T = 0.936; p = 0.364, respectively). The mean ridge height was 14.14 ± 3.53 mm in the control group and 14.64 ± 4.09 mm in the study group. The mean ridge width was 8.82 ± 0.93 mm in the control group and 8.04 ± 2.32 mm in the study group.(Fig. 2 ) 3.2 Microscopic Assessment 3.2.1 Hematoxylin and Eosin (H&E) Assessment The study group demonstrated newly formed fibrous bone undergoing remodeling into lamellar bone, with remnants of fibrous tissue incorporated within it. Bone surfaces were lined by osteoblasts, while osteocytes were visible within their lacunae (54.31 ± 8.60). Varying sizes of residual graft particles were embedded within trabecular bone and/or bone marrow connective tissue. These remnants appeared either osteo-integrated or encapsulated. Rows of active osteoblasts secreting osteoid tissue were observed adjacent to graft granules. In deeper regions of the specimens, the presence of lamellar bone reflected advanced bone remodeling. Residual graft particles were frequently in contact with osteoblasts producing osteoid and new woven bone, indicating ongoing osteogenesis and dynamic remodeling. The intertrabecular spaces were filled with fibrous connective tissue showing abundant vascularization. Numerous thin-walled capillaries surrounding the graft material suggested active angiogenesis and healing. No necrosis, foreign body reaction, or multinucleated giant cells were detected. The well-developed extracellular matrix appeared to support the integration of osteoid tissue with the graft interface. In a few specimens, a mild inflammatory response was noted, which may have contributed to the healing process (Fig. 3 A). The control group showed viable bone with no empty lacunae or morphological abnormalities. The bone marrow space was predominantly filled with loose connective tissue, with no evidence of inflammatory cell infiltration or bacterial infection. Vascularization was evident near the newly formed trabeculae. The bone tissue displayed thin lamellar bone, with areas of woven bone also present (40.05 ± 7.03). The trabecular surfaces were consistently lined by a layer of osteogenic cells. Occasional small clusters of round cells were observed within the adipose fibrovascular connective tissue of the intertrabecular spaces or at the specimen periphery (Fig. 3 B). Values for bone area in both groups were presented in Table 1 . A highly statistically significant difference was detected between the study and control groups (T = 3.633; p = 0.003). The mean bone area was markedly higher in the bone graft group (54.31 ± 8.60) compared to the control group (40.05 ± 7.03). 3.2.2 Masson’s Trichrome Assessment It enabled clear differentiation of mineralized bone matrix, osteoid, and fibrous connective tissue. Mineralized bone exhibited an organized lamellar structure with the graft material and active osteoblast lining stained with green/blue, while unmineralized osteoid appeared red, and fibrous connective tissue was stained green (Fig. 3 C & D). Multiple variables such as bone area, intertrabecular tissue, osteoid tissue were listed in Table 1 in the form of means ± standard deviations and revealed highly statistically significant between both groups. Bone area: The mean bone area was significantly greater in the study group (198 ± 53.4) compared with the control group (136 ± 41.6), with T = 10.01; p < 0.001. Intertrabecular tissue: The mean intertrabecular tissue was significantly reduced in the study group (122.5 ± 65.2) compared to the control group (177.8 ± 42.9) (T = 13.82; p < 0.001). Osteoid tissue: The mean osteoid tissue was also significantly lower in the study group (109.4 ± 33.8) relative to the control group (146.1 ± 11.3) (T = 11.3; p = 0.002). 3.2.3 Immunohistochemical OPN Assessment Osteopontin expression was markedly stronger in the study group compared with the control group. The immunoreactivity was most prominent at the periphery of the newly formed trabeculae. In addition, increased staining was observed in bone marrow cells and some connective tissue cells surrounding the trabeculae. In the control group, OPN immune reactivity was limited to the bone trabeculae boundaries with scanty expression of the connective tissue (Fig. 3 E & F). Quantitative analysis revealed a highly statistically significant difference (Table 1 ). While the mean OPN immunoreactivity was 60.82 ± 14.91 in the bone graft group compared to 16.09 ± 10.11 in the control group (T = 4.135; p = 0.001). Table 1 Distributions between the studied and control groups Study group (Mean ± SD) Control group (Mean ± SD) T test P value Immediate bone density (CBCT) 545.97 ± 131 -178.9 ± 80.17 13.95 < 0.001 4 months bone density (CBCT) 748.66 ± 90.19 514.33 ± 177.58 3.359 < 0.001 Alveolar ridge height (CBCT) 14.14 ± 3.53 14.64 ± 4.09 0.267 0.793 Alveolar ridge width (CBCT) 8.82 ± 0.93 8.04 ± 2.32 0.936 0.364 Bone area (H&E) 54.31 ± 8.60 40.05 ± 7.03 3.633 0.003 Bone trabeculae (MT) 198.1 ± 53.4 136.5 ± 41.6 10.01 0.001 Intertrabecular tissue (MT) 122.5 ± 65.2 177.8 ± 42.9 13.82 0.001 Osteoid tissue (MT) 109.4 ± 33.8 146.1 ± 58.3 11.30 0.002 Osteopontin (IHC) 60.82 ± 14.91 16.09 ± 10.11 4.135 0.001 4 Discussion The purpose of this clinical trial was to evaluate the histologic and histomorphometric outcomes of xenograft used in socket preservation prior to implant placement, in comparison with an un-grafted control group. Bone substitutes have been developed to address the drawbacks of autografts. While autogenous bone is considered the gold standard due to its histocompatibility, lack of immunogenic response, and its ability to support osteo-induction, osteogenesis, and osteogenesis, and osteogenesis, and osteo-conduction, harvesting was not always practical because it prolonged surgical procedures and might increase patient morbidity. 14 Tooth extraction affects negatively on the alveolar ridge (AR) through volumetric and geometric changes in edentulous site. Socket preservation for the space maintaining activity of the implanted material ensured decreased demand for sinus lift augmentation. 15 Moreover, it reduces the post-extraction bone loss, depending on the surgical technique and type of graft material used. 16 The goal of alveolar ridge preservation (ARP) is to maintain the dimensions and contours of the AR by placing a bone graft or substitute material into the socket immediately after tooth extraction during the remodeling process or implant rehabilitation. 17 Challenges to create an excellent bone quality which is suitable for implant placement to optimize the outcomes through using different grafting materials like allografts and xenografts for socket preservation. The graft material acts as a scaffold for new bone formation, preserving the volume and shape of the AR. 18 ' 19 Recent trials would try to adopt innovative approaches including plasma rich fibrin (PRF), injectable bone repair materials, and advanced hydrogel systems. 20 The alginate hydrogel was selected to achieve scaffold support to the xenograft material, providing a stable environment for cell attachment, proliferation, and differentiation. 21 The primary aim of this study was to study the S1-XB Xenograft containing hydrogel and to evaluate its effects on extraction socket healing in comparison to natural socket healing. The findings provided robust evidence that the xenograft group achieved significantly greater bone formation, maturation, and density, while no significant differences were observed in socket width, bone height, or osteopontin expression. These results add important suggestions to the literature on alveolar ridge preservation and the performance of graft materials. Histomorphometric analysis revealed that the study group had a markedly higher mean bone area, both in H & E staining (54.31 ± 8.60 vs. 40.05 ± 7.03; p = 0.003) and Masson's trichrome (47.48 ± 5.31 vs. 22.04 ± 4.79; p < 0.001) compared to control group. These results indicated not only a greater quantity of new bones but also more advanced collagen organization and mineralization in the grafted sockets. Such findings were consistent with previous studies reporting that xenografts effectively preserved alveolar bone and promoted superior bone quality. 22 ' 23 The use of hydrogel as a carrier likely enhanced these effects by providing scaffold stability and facilitating cellular infiltration and vascularization. 4 ' 23 No statistically significant differences were found in bone height (14.14 ± 3.53 mm vs. 14.64 ± 4.09 mm; p = 0.793) or width (8.04 ± 2.32 mm vs. 8.82 ± 0.93 mm; p = 0.364) between groups. This contrasted with some literature reporting improved ridge width preservation with grafting. 24 Several factors may explain this discrepancy follow-up duration: The four-month follow-up might be insufficient to observe the full extent of ridge remodeling, as significant dimensional changes often require at least six months to manifest. 25 Biological variability such as patient-related factors such as bone quality, systemic health, could influence healing outcomes. Measurement limitations such as variability in radiographic and clinical measurements might have masked subtle differences. Although a systematic review analysis of evidence-based ARP techniques stated that complete prevention of vertical resorption is still not implemented. Only one preservation technique not only stopped horizontal resorption but increased width of AR. 26 The study group demonstrated significantly higher bone density and Masson trichrome scores, supporting the hypothesis that the combination of xenograft and hydrogel enhanced both the quantity and quality of regenerated bone. This was likely due to improved osteo-conductivity and scaffold stability, as hydrogels had been shown to facilitate cell migration and vascularization. 4 Osteopontin (OPN) is a non-collagenous protein produced by osteoblasts throughout their maturation and by osteocytes, and it becomes incorporated into the mineralized bone matrix. In the present study, OPN showed strong immunoexpression at the interface between the remaining graft particles and surrounding tissue, suggesting that the grafting material stimulated osteoblastic differentiation. The mean OPN immunoexpression value was 60.82 ± 14.91 in the study group, compared with 16.09 ± 10.11 in the control group. The difference between the groups was 14.26, with a t-test result of 4.135 and a p-value of 0.001, indicating a statistically significant difference. Moreno et al., (2019) 27 confirmed that the marked increase in OPN immunoexpression in the study group was unlikely due to random variation and supported the hypothesis that the graft material enhanced osteoblastic activity. Adel-Khattab et al., (2020) 28 reported that the residual graft particles and the adjacent tissue reflected the stimulatory influence of the grafted material on osteoblastic differentiation. Although it is impossible to determine which method for ARP is better because of different evaluation and investigation methods. For successful implant placement and to avoid additional bone augmentation procedures, ARP was suggested. 26 Generalisability : Generalizability is limited by the single-center design, the inclusion of only male patients aged 21–40 years, and the restriction to maxillary posterior extraction sites. Results may therefore not apply to broader or medically compromised populations. Interpretation : Interpretation was consistent with the magnitude and precision of the treatment effects and did not rely solely on statistical significance. The conclusions reflect the clinical context and are balanced against study limitations. 5 Conclusion Bovine-derived xenograft with alginate hydrogel (S1-XB) significantly increased bone density and improved histological bone quality in maxillary posterior sockets compared to natural healing, without altering ridge height or width at 4 months. These results supported its use as an effective socket preservation material to optimize bone conditions for subsequent implant placement. Future studies should evaluate larger, more diverse populations, extend follow-up to assess long-term volume stability, and correlate histological findings with implant stability and survival. Comparative trials with other xenografts or graft carriers would further clarify the relative advantages of hydrogel-based formulations. Abbreviations CBCT Cone-Beam Computed Tomography ARP Alveolar ridge preservation. Declarations Acknowledgements Thanks to the patients who participated the follow-up Authors’ contributions MAM and MHE and MAE contributed to design and operation of the surgical procedure. MAM and MNE contributed to data collection specimen preparation and analysis and drafting article. All authors read and approved of the final manuscript. Funding This study was funded by the author MAM Conflict of interest: The authors declare no conflicts of interest. Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study protocol was evaluated and approved by the ethical committee in Suez Canal University, Faculty of Dentistry ,(Ref. 2022-547). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided written informed consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Authors details Department of Oral and Maxillofacial Surgery, Suez Canal University, Faculty of Dentistry Ismalia, Egypt 1,2,4 Department of Oral Pathology, Suez Canal University, Faculty of Dentistry, Ismalia, Egypt 3 References Tan WL, Wong TL, Wong MC, Lang NP. A systematic review of post‐extractional alveolar hard and soft tissue dimensional changes in humans. Clinical oral implants research. 2012 Feb; 23:1–21. dos Santos Canellas JV, Medeiros PJ, da Silva Figueredo CM, Fischer RG, Ritto FG. 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Bone regeneration and graft material resorption in extraction sockets grafted with bioactive silica-calcium phosphate composite versus non-grafted sockets: clinical, radiographic, and histological findings. Journal of Periodontal & Implant Science. 2020 Nov 13;50(6):418. Additional Declarations No competing interests reported. Supplementary Files CONSORT2025Marwan.docx 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. 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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-8223707","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":556411233,"identity":"b4d74a94-7fb0-4094-b4cc-e8b2e7384661","order_by":0,"name":"Marwan Aboul 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15:37:38","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72394,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/dcb1815e0cab953b6fc502ea.html"},{"id":97895386,"identity":"57c99582-3296-4ac8-abb2-6763b3f50a36","added_by":"auto","created_at":"2025-12-10 15:34:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14876,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/28d298686db47d3021ccc07c.png"},{"id":97721022,"identity":"afa55c0f-3fb1-4c16-b2e0-fd85a4b7b6cc","added_by":"auto","created_at":"2025-12-08 15:37:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":476370,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 1: \u003c/strong\u003ePhotographs showing (A) atraumatic surgical extraction. (B) Socket immediately after extraction. (C) Packing of bone graft inside the empty socket after curettage. (D \u0026amp; E) Suturing after bone application. (F \u0026amp; G) Healing after 4 months and prior to drilling. (H) Harvested bone inside the trephine bur. (I) Harvested bone in 10% formalin solution.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/f7142345a4d747dc9039d15e.png"},{"id":97895941,"identity":"f4df82a7-83fd-475f-ab83-ecf41108e3f3","added_by":"auto","created_at":"2025-12-10 15:35:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":152551,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2: \u003c/strong\u003eCBCT scans after extraction at baseline and at 4 months postoperatively.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/e8da7544a9d8ddc4402ccf7e.png"},{"id":97721030,"identity":"b0327ad2-44ed-4ff1-b1d9-8c41279709d0","added_by":"auto","created_at":"2025-12-08 15:37:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":795101,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 3: \u003c/strong\u003ePhotomicrographs of the study group: (A) H \u0026amp; E-stained section showing thick trabeculae of woven bone and evidence of residual material in the with non-inflamed connective tissue. (C) Masson Trichrome shows many calcified areas with less osteoid areas in a remodeling process. (E) Strong positive OPN immunoreactivity at the graft/bone interface. The control group: (B) H \u0026amp; E-stained section shows thin trabeculae of woven bone with intervening non-inflamed connective tissue. (D) Masson Trichrome shows trabeculae of woven bone with less calcified areas. (F) Weak positive OPN immunoreactivity at the osteoblastic lining of newly formed bone.\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/9931731afeac006f85fe8212.png"},{"id":102191387,"identity":"c32d728c-5ba1-47d0-8baf-eaf56b656da8","added_by":"auto","created_at":"2026-02-09 09:13:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2784894,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/59adb9dd-79fa-4260-b77b-b4dfd6888dfc.pdf"},{"id":97895127,"identity":"8d7cbd59-714b-4557-9ec9-f0de5365a501","added_by":"auto","created_at":"2025-12-10 15:33:38","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32966,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2025Marwan.docx","url":"https://assets-eu.researchsquare.com/files/rs-8223707/v1/9e0c34a9ebd5727bfdc11e4a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Radiographic and Histomorphometric Analysis of a Xenograft S1-XB for Socket Preservation in Maxillary Posterior Teeth: A Randomized Controlled Clinical Study","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eThe alveolar process always has resorptive changes as natural consequence to tooth extraction, occurring commonly after tooth removal. This has been significantly more obvious on empty socket buccal aspect where an increased loss of bone volume has been noticed.\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe process of natural healing is composed of a complex and dynamic series of events. It starts with blood clot formation immediately which serves as a protective barrier that covers the exposed bone and nerve endings in the socket. It also provides a scaffold for the infiltration of granulation tissue. The formation of a stable clot is essential to prevent alveolar osteitis, commonly known as dry socket. Then, the inflammatory phase involves the recruitment of inflammatory cells to the site to combat infection and clear out debris. Proliferative phase fills the socket with granulation tissue rich in collagen, fibroblasts, and capillaries. Bone formation begins at the periphery of the socket and progresses towards the center. This woven bone eventually matures into harder lamellar bone. Maturation and remodeling to achieve the density and architecture of the original bone.\u003csup\u003e2\u003c/sup\u003e' \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSocket preservation is a crucial procedure following tooth extraction, aimed at minimizing bone resorption, and maintaining the contour and volume of the alveolar ridge. This is particularly important in areas where future prosthetic replacements or implants are planned. Moreover, it reduces the necessity for extensive ridge augmentation procedures in the future.\u003csup\u003e4\u003c/sup\u003e Several techniques and materials are used in socket preservation to achieve optimal outcomes. Bone graft has great importance in filling the socket post-extraction, supporting new bone formation and preventing the collapse of the socket walls.\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe earliest recorded use of a bone graft dates back to 1682, during repair of a cranial defect using a graft obtained from the skull of a deceased dog.\u003csup\u003e6\u003c/sup\u003e Since that time, bone grafts and their substitutes have become integral in clinical practice. A bone graft is generally defined as viable tissue was transplanted into a bone defect, to stimulate bone regeneration and healing either alone or in combination with other materials, with the capacity.\u003csup\u003e7\u003c/sup\u003e In comparison, a bone substitute serves the same purpose but does not contain living cells; instead, it is composed of a mineralized bone matrix of either natural or synthetic origin.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAllografts are limited by drawbacks such as the risk of donor tissue rejection and potential disease transmission, including HIV and hepatitis. Autografts, while considered the gold standard, are also associated with notable disadvantages, including limited tissue availability, the requirement for a second surgical site, and the resulting donor site pain and morbidity.\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTo overcome these challenges, alternative grafting strategies have been explored to optimize clinical outcomes. Among these, synthetic bone substitutes and xenografts demonstrate distinct advantages in terms of availability and cost-effectiveness. Notably, xenograft-based hydrogels have been successfully utilized in humans for socket preservation following the extraction of impacted mandibular molars.\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAn ideal bone substitute is expected to combine several key properties, including affordability, ease of handling, minimal patient morbidity, low immunogenicity, and angiogenic potential. However, most commercially available products have yet to demonstrate all these characteristics simultaneously.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eBased on this gap, the present randomized controlled clinical study aimed to assess the radiographic and histomorphometric outcomes of S1-XB xenograft for the preservation of extraction sockets in maxillary posterior teeth, compared with natural healing. We hypothesized that the use of xenograft would lead to significantly improved bone density and superior histological bone quality after four months, without compromising ridge dimensions.\u003c/p\u003e\u003cp\u003eThis randomized clinical trial adhered to the CONSORT 2010 recommendations for reporting parallel-group randomized trials.\u003c/p\u003e"},{"header":"2 Patients and Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Trial Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a parallel-group, two-arm, 1:1 randomized controlled clinical trial. No changes to the trial design, eligibility criteria, or outcome measures were made after trial commencement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Ethical Approval and Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial was approved by the Research Ethics Committee of Suez Canal University (No. 547/2022).\u003cbr\u003e\u0026nbsp;The study was not prospectively registered; however, the full protocol was approved before participant enrolment and is available from the corresponding author upon reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Recruitment Period\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants were recruited between \u003cstrong\u003e[August\u0026ndash;2022]\u003c/strong\u003e and \u003cstrong\u003e[December\u0026ndash;2022]\u003c/strong\u003e, and all follow-up procedures were completed by \u003cstrong\u003e[December\u0026ndash;2024]\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSample Size:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eG* Power analysis version 3.1.9.7 was used to perform the calculation of the sample size. Based on the results of a previous study,\u003csup\u003e12\u003c/sup\u003e alpha level = 0.05, beta = 0.2, power = 80% and absolute error or precision (d) = 1.51. The predicted sample size (n) was 16 samples that were divided equally in both groups. Eight samples in each group were in line with a previous study that tested it in similar subjects.\u003csup\u003e13\u003c/sup\u003e The calculation was based on detecting a clinically meaningful difference in \u003cstrong\u003ebone density (primary outcome)\u003c/strong\u003e at 4 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Patients Randomization and Allocation:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSequence generation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA simple randomization sequence (1:1) was generated using a computer-based randomizer\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003e\u003cstrong\u003ewww.randomizer.org\u003c/strong\u003e\u003cstrong\u003e).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAllocation concealment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAllocation was concealed using sequentially numbered, opaque, sealed envelopes prepared by an independent research coordinator not involved in enrolment or treatment.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation:\u003cbr\u003e\u003c/strong\u003eThe random sequence was generated by an independent statistician.\u003cbr\u003eParticipants were enrolled by a research coordinator.\u003cbr\u003eThe surgeon opened the next sealed envelope to assign the participant to the study or control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6 Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to the nature of the intervention, blinding of the surgeon and participants was not feasible.\u003cbr\u003e\u0026nbsp;However:\u003cbr\u003e\u0026nbsp;Radiographic outcome assessors and Histopathology examiners\u003cbr\u003e\u0026nbsp;were fully blinded to group allocation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.7 Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome:\u003c/strong\u003e\u003cbr\u003e\u0026ndash; \u003cstrong\u003eBone density (HU)\u003c/strong\u003e measured by CBCT at baseline and at 4 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp; Ridge height and ridge width (CBCT).\u003cbr\u003e\u0026nbsp; Histomorphometric measures (H\u0026amp;E and Masson\u0026apos;s trichrome): bone area, osteoid tissue, intertrabecular tissue.\u003cbr\u003e\u0026nbsp;Osteopontin (OPN) immunoexpression (% area).\u003c/p\u003e\n\u003cp\u003eNo outcome changes were made after trial initiation.\u003c/p\u003e\n\u003cp\u003eSixteen male patients aged 21\u0026ndash;40 years requiring extraction of hopeless maxillary posterior teeth, with sites suitable for future implant placement were randomly assigned (1:1) using a web-based randomizer (www.randomizer.org). Study group (n=8) extracted their teeth, and the sockets were grafted using bovine derived xenograft with alginate hydrogel material (hydroxypropyl methylcellulose) using S1-XB (Medpark/Korea). Control group (n=8) extracted their teeth and were allowed to undergo natural healing. Blinding the surgeon was not feasible due to the nature of the intervention. However, both outcome assessors and histological examiners were blinded to group allocation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 Harms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll adverse events and complications were monitored at each visit. No intraoperative or postoperative complications or adverse events occurred in either group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.9 Inclusion criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026middot; Male patients aged between 21 and 40 years.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026middot; Participants in good general health.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Presence of a single extraction site in the maxillary premolar or molar region.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Adequate mesiodistal and interocclusal space to accommodate implant restoration.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Extraction site suitable for subsequent replacement with a dental implant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.10 Exclusion criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026middot; Female patients.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Current smokers.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Patients receiving chronic medications known to affect bone turnover (e.g., bisphosphonates).\u003c/p\u003e\n\u003cp\u003e\u0026middot; Patients with psychological disorders or uncontrolled systemic conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.11 Surgical Procedure\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll extractions performed by the same surgeon under local anesthesia (4% articaine with 1:100,000 epinephrine) using an atraumatic technique, which involved periotomes, luxators, and tooth sectioning when necessary. Following extraction, all sockets were thoroughly curetted and irrigated with sterile saline (Figure 1).\u003c/p\u003e\n\u003cp\u003eIn the study group, S1-XB granules were hydrated with 0.5\u0026ndash;1 mL of sterile saline to achieve a workable consistency, then gently packed into the socket up to the crestal level and stabilized using 3-0 silk figure-of-eight sutures. In the control group, sockets were left to heal spontaneously without intervention.\u003c/p\u003e\n\u003cp\u003eAll patients received standardized postoperative instructions along with a 5-day course of antibiotics: amoxicillin 500 mg three / day (or azithromycin 500 mg once daily in case of allergy) in combination with metronidazole three / day. Analgesia was provided with 500 mg paracetamol up to three times daily as needed. Additionally, chlorhexidine 0.12% mouthrinse was prescribed twice daily, starting 24 hours after surgery and continuing for 7 days. Sutures were removed between 7 and 10 days postoperatively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 4 months, a full-thickness flap was raised under local anesthesia. Core biopsies were harvested from the planned implant site using a 2\u0026ndash;3 mm trephine to a depth of 2 mm without compromising implant stability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.16 \u0026nbsp;Radiographic Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCone-beam computed tomography (CBCT) scans (Scanora 3D) were obtained immediately after extraction at baseline and postponed at 4 months postoperatively to evaluate the following parameters: bone density that was measured in Hounsfield units (HU) at the center of the socket, ridge height that was determined by vertical distance from the crestal bone to a fixed reference point and ridge width that was measured at 3 mm apical to the crest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.17 \u0026nbsp; Microscopic Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBiopsies were fixed in 10% buffered formalin and decalcified in 10% EDTA for one week with regular renewal of the solution daily.\u0026nbsp;Then, the specimen was dehydrated, cleared in xylol, embedded in paraffin and sectioned using a microtome into thin paraffin sections 5 \u0026micro; thickness. Sections were stained with different stains according to manufacture instructions.\u003c/p\u003e\n\u003cp\u003eSamples were first stained with hematoxylin and eosin (H\u0026amp;E) to demonstrate the general tissue architecture, cellular distribution, and overall structural organization. Subsequently, sections were stained with Masson\u0026rsquo;s Trichrome (MTC) to allow both qualitative and quantitative assessment of bone trabeculae and osteoid tissue. Osteopontin (OPN) immunohistochemistry was used to assess the percentage of OPN expression area within the surrounding connective tissue.\u0026nbsp;The OPN poly-colonal antibody was purchased from\u0026nbsp;Thermo Fisher Scientific, Catalog\u003cstrong\u003e\u0026nbsp;#\u0026nbsp;\u003c/strong\u003ePA1-72061. Images were captured at \u0026times;400 magnification using a SOPTOP EX20 microscope with HD camera. ImageJ software was used to quantify area% from five standardized fields per section at oral pathology laboratory, Faculty of Dentistry, Suez Canal University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.18 Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgram of SPSS version 26.0 (IBM Corp., Armonk, NY, USA) was used in data analysis that were represented as mean \u0026plusmn; standard deviation (SD). Independent samples t-test was used between-group differences, while paired t-test was applied within-group changes over time at p-value \u0026lt;0.05 as statistically significant. All analyses were performed on an intention-to-treat basis, including all randomized participants.\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAll 16 randomized participants received the allocated intervention and completed the study. There were no post-randomization exclusions or losses to follow-up.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Radiographic Assessment\u003c/h2\u003e\u003cp\u003eSixteen patients completed the study with no dropouts. Baseline characteristics, including pre-extraction CBCT measurements, were comparable between groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Radiographic evaluation revealed greater radiopacity in the study group compared to the un-grafted control group. The mean bone density was 514.33\u0026thinsp;\u0026plusmn;\u0026thinsp;177.58 HU in the control group and 748.66\u0026thinsp;\u0026plusmn;\u0026thinsp;90.19 HU in the study group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The difference between groups was highly statistically significant (T\u0026thinsp;=\u0026thinsp;3.359; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eChanges in the ridge height and width from baseline to 4 months were minimal and showed no statistically significant differences between groups (T\u0026thinsp;=\u0026thinsp;0.267; p\u0026thinsp;=\u0026thinsp;0.793 and T\u0026thinsp;=\u0026thinsp;0.936; p\u0026thinsp;=\u0026thinsp;0.364, respectively). The mean ridge height was 14.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.53 mm in the control group and 14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09 mm in the study group. The mean ridge width was 8.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 mm in the control group and 8.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32 mm in the study group.(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Microscopic Assessment\u003c/h2\u003e\u003cdiv id=\"Sec17\" class=\"Section3\"\u003e\u003ch2\u003e3.2.1 Hematoxylin and Eosin (H\u0026amp;E) Assessment\u003c/h2\u003e\u003cp\u003eThe study group demonstrated newly formed fibrous bone undergoing remodeling into lamellar bone, with remnants of fibrous tissue incorporated within it. Bone surfaces were lined by osteoblasts, while osteocytes were visible within their lacunae (54.31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60). Varying sizes of residual graft particles were embedded within trabecular bone and/or bone marrow connective tissue. These remnants appeared either osteo-integrated or encapsulated. Rows of active osteoblasts secreting osteoid tissue were observed adjacent to graft granules. In deeper regions of the specimens, the presence of lamellar bone reflected advanced bone remodeling. Residual graft particles were frequently in contact with osteoblasts producing osteoid and new woven bone, indicating ongoing osteogenesis and dynamic remodeling. The intertrabecular spaces were filled with fibrous connective tissue showing abundant vascularization. Numerous thin-walled capillaries surrounding the graft material suggested active angiogenesis and healing. No necrosis, foreign body reaction, or multinucleated giant cells were detected. The well-developed extracellular matrix appeared to support the integration of osteoid tissue with the graft interface. In a few specimens, a mild inflammatory response was noted, which may have contributed to the healing process (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e\u003cp\u003eThe control group showed viable bone with no empty lacunae or morphological abnormalities. The bone marrow space was predominantly filled with loose connective tissue, with no evidence of inflammatory cell infiltration or bacterial infection. Vascularization was evident near the newly formed trabeculae. The bone tissue displayed thin lamellar bone, with areas of woven bone also present (40.05\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03). The trabecular surfaces were consistently lined by a layer of osteogenic cells. Occasional small clusters of round cells were observed within the adipose fibrovascular connective tissue of the intertrabecular spaces or at the specimen periphery (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eValues for bone area in both groups were presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A highly statistically significant difference was detected between the study and control groups (T\u0026thinsp;=\u0026thinsp;3.633; p\u0026thinsp;=\u0026thinsp;0.003). The mean bone area was markedly higher in the bone graft group (54.31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60) compared to the control group (40.05\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section3\"\u003e\u003ch2\u003e3.2.2 Masson\u0026rsquo;s Trichrome Assessment\u003c/h2\u003e\u003cp\u003eIt enabled clear differentiation of mineralized bone matrix, osteoid, and fibrous connective tissue. Mineralized bone exhibited an organized lamellar structure with the graft material and active osteoblast lining stained with green/blue, while unmineralized osteoid appeared red, and fibrous connective tissue was stained green (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC \u0026amp; D). Multiple variables such as bone area, intertrabecular tissue, osteoid tissue were listed in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e in the form of means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations and revealed highly statistically significant between both groups.\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eBone area: The mean bone area was significantly greater in the study group (198\u0026thinsp;\u0026plusmn;\u0026thinsp;53.4) compared with the control group (136\u0026thinsp;\u0026plusmn;\u0026thinsp;41.6), with T\u0026thinsp;=\u0026thinsp;10.01; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eIntertrabecular tissue: The mean intertrabecular tissue was significantly reduced in the study group (122.5\u0026thinsp;\u0026plusmn;\u0026thinsp;65.2) compared to the control group (177.8\u0026thinsp;\u0026plusmn;\u0026thinsp;42.9) (T\u0026thinsp;=\u0026thinsp;13.82; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eOsteoid tissue: The mean osteoid tissue was also significantly lower in the study group (109.4\u0026thinsp;\u0026plusmn;\u0026thinsp;33.8) relative to the control group (146.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3) (T\u0026thinsp;=\u0026thinsp;11.3; p\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section3\"\u003e\u003ch2\u003e3.2.3 Immunohistochemical OPN Assessment\u003c/h2\u003e\u003cp\u003eOsteopontin expression was markedly stronger in the study group compared with the control group. The immunoreactivity was most prominent at the periphery of the newly formed trabeculae. In addition, increased staining was observed in bone marrow cells and some connective tissue cells surrounding the trabeculae. In the control group, OPN immune reactivity was limited to the bone trabeculae boundaries with scanty expression of the connective tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE \u0026amp; F). Quantitative analysis revealed a highly statistically significant difference (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). While the mean OPN immunoreactivity was 60.82\u0026thinsp;\u0026plusmn;\u0026thinsp;14.91 in the bone graft group compared to 16.09\u0026thinsp;\u0026plusmn;\u0026thinsp;10.11 in the control group (T\u0026thinsp;=\u0026thinsp;4.135; p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistributions between the studied and control groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT test\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmediate bone density (CBCT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e545.97\u0026thinsp;\u0026plusmn;\u0026thinsp;131\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-178.9\u0026thinsp;\u0026plusmn;\u0026thinsp;80.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4 months bone density (CBCT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e748.66\u0026thinsp;\u0026plusmn;\u0026thinsp;90.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e514.33\u0026thinsp;\u0026plusmn;\u0026thinsp;177.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.359\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlveolar ridge height (CBCT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.267\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.793\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlveolar ridge width (CBCT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e8.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e8.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.936\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.364\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone area\u003c/p\u003e\u003cp\u003e(H\u0026amp;E)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e54.31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e40.05\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.633\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone trabeculae (MT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e198.1\u0026thinsp;\u0026plusmn;\u0026thinsp;53.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e136.5\u0026thinsp;\u0026plusmn;\u0026thinsp;41.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntertrabecular tissue (MT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e122.5\u0026thinsp;\u0026plusmn;\u0026thinsp;65.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e177.8\u0026thinsp;\u0026plusmn;\u0026thinsp;42.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOsteoid tissue (MT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e109.4\u0026thinsp;\u0026plusmn;\u0026thinsp;33.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e146.1\u0026thinsp;\u0026plusmn;\u0026thinsp;58.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOsteopontin\u003c/p\u003e\u003cp\u003e(IHC)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e60.82\u0026thinsp;\u0026plusmn;\u0026thinsp;14.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e16.09\u0026thinsp;\u0026plusmn;\u0026thinsp;10.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThe purpose of this clinical trial was to evaluate the histologic and histomorphometric outcomes of xenograft used in socket preservation prior to implant placement, in comparison with an un-grafted control group. Bone substitutes have been developed to address the drawbacks of autografts. While autogenous bone is considered the gold standard due to its histocompatibility, lack of immunogenic response, and its ability to support osteo-induction, osteogenesis, and osteogenesis, and osteogenesis, and osteo-conduction, harvesting was not always practical because it prolonged surgical procedures and might increase patient morbidity.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTooth extraction affects negatively on the alveolar ridge (AR) through volumetric and geometric changes in edentulous site. Socket preservation for the space maintaining activity of the implanted material ensured decreased demand for sinus lift augmentation.\u003csup\u003e15\u003c/sup\u003e Moreover, it reduces the post-extraction bone loss, depending on the surgical technique and type of graft material used.\u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe goal of alveolar ridge preservation (ARP) is to maintain the dimensions and contours of the AR by placing a bone graft or substitute material into the socket immediately after tooth extraction during the remodeling process or implant rehabilitation. \u003csup\u003e17\u003c/sup\u003e Challenges to create an excellent bone quality which is suitable for implant placement to optimize the outcomes through using different grafting materials like allografts and xenografts for socket preservation. The graft material acts as a scaffold for new bone formation, preserving the volume and shape of the AR. \u003csup\u003e18\u003c/sup\u003e' \u003csup\u003e19\u003c/sup\u003e Recent trials would try to adopt innovative approaches including plasma rich fibrin (PRF), injectable bone repair materials, and advanced hydrogel systems.\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe alginate hydrogel was selected to achieve scaffold support to the xenograft material, providing a stable environment for cell attachment, proliferation, and differentiation.\u003csup\u003e21\u003c/sup\u003e The primary aim of this study was to study the S1-XB Xenograft containing hydrogel and to evaluate its effects on extraction socket healing in comparison to natural socket healing.\u003c/p\u003e\u003cp\u003eThe findings provided robust evidence that the xenograft group achieved significantly greater bone formation, maturation, and density, while no significant differences were observed in socket width, bone height, or osteopontin expression. These results add important suggestions to the literature on alveolar ridge preservation and the performance of graft materials.\u003c/p\u003e\u003cp\u003eHistomorphometric analysis revealed that the study group had a markedly higher mean bone area, both in H \u0026amp; E staining (54.31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60 vs. 40.05\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03; p\u0026thinsp;=\u0026thinsp;0.003) and Masson's trichrome (47.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.31 vs. 22.04\u0026thinsp;\u0026plusmn;\u0026thinsp;4.79; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to control group. These results indicated not only a greater quantity of new bones but also more advanced collagen organization and mineralization in the grafted sockets. Such findings were consistent with previous studies reporting that xenografts effectively preserved alveolar bone and promoted superior bone quality.\u003csup\u003e22\u003c/sup\u003e' \u003csup\u003e23\u003c/sup\u003e The use of hydrogel as a carrier likely enhanced these effects by providing scaffold stability and facilitating cellular infiltration and vascularization.\u003csup\u003e4\u003c/sup\u003e' \u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNo statistically significant differences were found in bone height (14.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.53 mm vs. 14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09 mm; p\u0026thinsp;=\u0026thinsp;0.793) or width (8.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32 mm vs. 8.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 mm; p\u0026thinsp;=\u0026thinsp;0.364) between groups. This contrasted with some literature reporting improved ridge width preservation with grafting.\u003csup\u003e24\u003c/sup\u003e Several factors may explain this discrepancy follow-up duration: The four-month follow-up might be insufficient to observe the full extent of ridge remodeling, as significant dimensional changes often require at least six months to manifest.\u003csup\u003e25\u003c/sup\u003e Biological variability such as patient-related factors such as bone quality, systemic health, could influence healing outcomes. Measurement limitations such as variability in radiographic and clinical measurements might have masked subtle differences. Although a systematic review analysis of evidence-based ARP techniques stated that complete prevention of vertical resorption is still not implemented. Only one preservation technique not only stopped horizontal resorption but increased width of AR.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe study group demonstrated significantly higher bone density and Masson trichrome scores, supporting the hypothesis that the combination of xenograft and hydrogel enhanced both the quantity and quality of regenerated bone. This was likely due to improved osteo-conductivity and scaffold stability, as hydrogels had been shown to facilitate cell migration and vascularization.\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eOsteopontin (OPN) is a non-collagenous protein produced by osteoblasts throughout their maturation and by osteocytes, and it becomes incorporated into the mineralized bone matrix. In the present study, OPN showed strong immunoexpression at the interface between the remaining graft particles and surrounding tissue, suggesting that the grafting material stimulated osteoblastic differentiation. The mean OPN immunoexpression value was 60.82\u0026thinsp;\u0026plusmn;\u0026thinsp;14.91 in the study group, compared with 16.09\u0026thinsp;\u0026plusmn;\u0026thinsp;10.11 in the control group. The difference between the groups was 14.26, with a t-test result of 4.135 and a p-value of 0.001, indicating a statistically significant difference. Moreno et al., (2019) \u003csup\u003e27\u003c/sup\u003e confirmed that the marked increase in OPN immunoexpression in the study group was unlikely due to random variation and supported the hypothesis that the graft material enhanced osteoblastic activity. Adel-Khattab et al., (2020) \u003csup\u003e28\u003c/sup\u003e reported that the residual graft particles and the adjacent tissue reflected the stimulatory influence of the grafted material on osteoblastic differentiation. Although it is impossible to determine which method for ARP is better because of different evaluation and investigation methods. For successful implant placement and to avoid additional bone augmentation procedures, ARP was suggested.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eGeneralisability\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eGeneralizability is limited by the single-center design, the inclusion of only male patients aged 21\u0026ndash;40 years, and the restriction to maxillary posterior extraction sites. Results may therefore not apply to broader or medically compromised populations.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInterpretation\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eInterpretation was consistent with the magnitude and precision of the treatment effects and did not rely solely on statistical significance. The conclusions reflect the clinical context and are balanced against study limitations.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eBovine-derived xenograft with alginate hydrogel (S1-XB) significantly increased bone density and improved histological bone quality in maxillary posterior sockets compared to natural healing, without altering ridge height or width at 4 months. These results supported its use as an effective socket preservation material to optimize bone conditions for subsequent implant placement. Future studies should evaluate larger, more diverse populations, extend follow-up to assess long-term volume stability, and correlate histological findings with implant stability and survival. Comparative trials with other xenografts or graft carriers would further clarify the relative advantages of hydrogel-based formulations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCBCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCone-Beam Computed Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eARP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAlveolar ridge preservation.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks to the patients who participated the follow-up\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMAM and MHE and MAE contributed to design and operation of the surgical procedure. MAM and MNE contributed to data collection specimen preparation and analysis and drafting article. All authors read and approved of the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the author MAM\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was evaluated and approved by the ethical committee in Suez Canal University, Faculty of Dentistry ,(Ref. 2022-547). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors details\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Oral and Maxillofacial Surgery, Suez Canal University, Faculty of Dentistry Ismalia, Egypt\u003csup\u003e1,2,4\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Oral Pathology, Suez Canal University, Faculty of Dentistry, Ismalia, Egypt \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Tan WL, Wong TL, Wong MC, Lang NP. 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Egyptian Dental Journal. 2022 Apr 1;68(2):1423-33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Huang X, Xie M, Xie Y, Mei F, Lu X, Li X, Chen L. The roles of osteocytes in alveolar bone destruction in periodontitis. Journal of Translational Medicine. 2020 Dec 11;18(1):479.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e. Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian journal of psychological medicine. 2013 Apr;35(2):121-6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. Journal of periodontology. 2008 Aug;79(8):1370-7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Hoexter DL. Bone regeneration graft materials. Journal of oral implantology. 2002 Dec 1;28 (6):290-4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Rasperini G, Canullo L, Dellavia C, Pellegrini G, Simion M. Socket grafting in the posterior maxilla reduces the need for sinus augmentation. International Journal of Periodontics \u0026amp; Restorative Dentistry. 2010 May 1;30(3).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Bayat N, Ghavimi MA, Rahimipour K, Razi S, Esmaeili F. Radiographic texture analysis of the hard tissue changes following socket preservation with allograft and xenograft materials for dental implantation: A randomized clinical trial. Oral and Maxillofacial Surgery. 2024 Jun;28(2):705\u0026thinsp;\u0026minus;\u0026thinsp;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e De Angelis N, Colombo E, Yumang C, Canepa C, Baldi D, Bagnasco F, Pesce P. Socket Preservation in Dentistry: a Comprehensive Review on Efficacy, Tissue Volume Maintenance, and Economic Considerations with Focus on Membrane Types and Bone Regeneration Dynamics. Current Oral Health Reports. 2024 Sep;11(3):177\u0026thinsp;\u0026minus;\u0026thinsp;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Zampara E, Alshammari M, De Bortoli J, Mullings O, Gkisakis IG, Benalc\u0026aacute;zar Jalkh EB, Tovar N, Coelho PG, Witek L. A histologic and histomorphometric evaluation of an allograft, xenograft, and alloplast graft for alveolar ridge preservation in humans: a randomized controlled clinical trial. Journal of Oral Implantology. 2022 Dec 1;48(6):541-9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Mardas N, Macbeth N, Donos N, Jung RE, Zuercher AN. Is alveolar ridge preservation an overtreatment? Periodontology 2000. 2023 Oct;93(1):289\u0026ndash;308.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Kim S, Kim SG. Advancements in alveolar bone grafting and ridge preservation: a narrative review on materials, techniques, and clinical outcomes. Maxillofacial Plastic and Reconstructive Surgery. 2024 Apr 16;46(1):14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Kavand A, Noverraz F, Gerber-Lemaire S. Recent advances in alginate-based hydrogels for cell transplantation applications. Pharmaceutics. 2024 Mar 27;16(4):469.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Ara\u0026uacute;jo MG, Lindhe J. Dimensional ridge alterations following tooth extraction. An experimental study in the dog. Journal of clinical periodontology. 2005 Feb;32(2):212-8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Papageorgiou SN, Papageorgiou PN, Deschner J, G\u0026ouml;tz W. Comparative effectiveness of natural and synthetic bone grafts in oral.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetz JP. Ridge preservation with freeze‐dried bone allograft and a collagen membrane compared to extraction alone for implant site development: A clinical and histologic study in humans. Journal of periodontology. 2003 Jul;74(7):990-9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. International journal of periodontics \u0026amp; restorative dentistry. 2003 Aug 1;23(4).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Stumbras A, Kuliesius P, Januzis G, Juodzbalys G. Alveolar ridge preservation after tooth extraction using different bone graft materials and autologous platelet concentrates: a systematic review. Journal of oral \u0026amp; maxillofacial research. 2019 Mar 31;10(1): e2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Moreno AR, Magdaleno MO, Islas MM, Mercado JA, del Pilar Goldaracena Azuara M, Cruz ER, Ram\u0026iacute;rez GF. Postextraction alveolar preservation and use of the crown of the extracted tooth as a temporary restoration. Case Reports in Dentistry. 2019;2019(1):4262067.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Adel-Khattab D, Afifi NS, El Sadat SM, Aboul-Fotouh MN, Tarek K, Horowitz RA. Bone regeneration and graft material resorption in extraction sockets grafted with bioactive silica-calcium phosphate composite versus non-grafted sockets: clinical, radiographic, and histological findings. Journal of Periodontal \u0026amp; Implant Science. 2020 Nov 13;50(6):418.\u003c/span\u003e\u003c/li\u003e\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":"Socket preservation, Xenograft, Bone density, Histomorphometry, Osteopontin","lastPublishedDoi":"10.21203/rs.3.rs-8223707/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8223707/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSocket preservation aims to minimize post-extraction ridge resorption. This randomized controlled clinical trial evaluated the radiographic and histomorphometric outcomes of a bovine-derived xenograft combined with alginate hydrogel (S1-XB) compared with natural healing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study investigated the radiographic and histomorphometric outcomes of socket preservation with a bovine-derived xenograft combined with alginate hydrogel (S1-XB) compared to natural healing in maxillary posterior extraction sites.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSixteen male patients (21–40 years) requiring atraumatic extraction of maxillary posterior teeth were randomly assigned (1:1) to S1-XB grafting (n = 8) or natural healing (n = 8). Cone-beam computed tomography (CBCT) was performed immediately post-extraction and after 4 months to assess bone density, ridge height, and ridge width. Core biopsies harvested at 4 months were analyzed using H\u0026amp;E, Masson's trichrome, and osteopontin immunohistochemistry. The primary outcome was CBCT-based bone density at 4 months. Secondary outcomes included ridge dimensions, bone area, osteoid, intertrabecular tissue, and osteopontin expression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll 16 randomized participants completed the study. Bone density was significantly higher in the grafted group compared with controls (748.66 ± 90.19 HU vs. 514.33 ± 177.58 HU; p \u0026lt; 0.001). Histomorphometry showed significantly greater bone area and lower osteoid and intertrabecular tissue in the grafted sockets. Ridge height and width did not differ significantly between groups. No adverse events occurred.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS1-XB xenograft significantly enhanced bone density and histological bone quality without altering ridge dimensions at 4 months. The material appears effective for socket preservation prior to implant placement.\u003c/p\u003e\n\u003cp\u003eTrial was retrospectively registered on Clinicaltrials.gov , TNR: NCT07250256 , 11/25/2025\u003c/p\u003e","manuscriptTitle":"Radiographic and Histomorphometric Analysis of a Xenograft S1-XB for Socket Preservation in Maxillary Posterior Teeth: A Randomized Controlled Clinical Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 15:37:33","doi":"10.21203/rs.3.rs-8223707/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":"2aba8807-2b07-4342-bb7d-085f9b719839","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T09:12:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 15:37:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8223707","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8223707","identity":"rs-8223707","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}