Three-year results of a prospective, controlled clinical study evaluating treatment of intra- bony defects with PRF or EMD- a randomized control trial

Three-year results of a prospective, controlled clinical study evaluating treatment of intra- bony defects with PRF or EMD- a randomized control trial | 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 Three-year results of a prospective, controlled clinical study evaluating treatment of intra- bony defects with PRF or EMD- a randomized control trial Ferenc Dőri, Florina Németh, Nicole Arweiler, Eleonora Solyom This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9163030/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Periodontal regeneration of intrabony defects remains clinically challenging. Enamel matrix derivative (EMD) is a well-documented biologic agent, whereas platelet-rich fibrin (PRF) has emerged as a promising autologous alternative. This prospective controlled clinical study aimed to compare the long-term clinical outcomes of PRF and EMD in the treatment of periodontal intrabony defects. Methods Thirty patients with chronic periodontitis and at least one intrabony defect [probing pocket depth (PPD) ≥ 6 mm; intrabony component ≥ 3 mm] were randomly assigned to surgery using PRF (test group) or EMD (control group). Clinical parameters, including PPD, gingival recession (GR), clinical attachment level (CAL), and bone sounding (BS), were recorded at baseline, 6 months, and 3 years postoperatively. Appropriate parametric and nonparametric statistical tests were applied (α = 0.05). Results Twenty-six patients completed the 3-year follow-up. In the PRF group, mean PPD was reduced from 8.85 ± 2.27 mm to 4.38 ± 1.95 mm at 6 months and measured 5.15 ± 2.03 mm at 3 years (p < 0.001). Mean CAL improved from 10.31 ± 1.75 mm to 5.92 ± 2.36 mm at 6 months and remained stable at 6.53 ± 2.26 mm after 3 years (p < 0.001). In the EMD group, mean PPD decreased from 8.08 ± 2.53 mm to 4.46 ± 1.27 mm at 6 months and was 4.77 ± 2.49 mm at 3 years, while CAL improved from 9.23 ± 2.62 mm to 7.31 ± 1.49 mm and 6.69 ± 2.75 mm, respectively (p < 0.001). At 6 months, GR was significantly lower in the PRF group compared with the EMD group (1.54 ± 1.56 mm vs. 2.85 ± 1.34 mm; p = 0.031). No statistically significant intergroup differences were observed for any parameter at 3 years. Conclusions PRF and EMD provided comparable and stable long-term clinical improvements after surgical treatment of intrabony periodontal defects. PRF demonstrated a short-term advantage in reducing postoperative gingival recession. Surgery with PRF may represent a reliable autologous alternative to EMD in periodontal therapy. Trial Registration: The study was registered on ClinicalTrials.gov, registration number: NCT07183631, registration date:2025.09.14.; retrospectively registered. Periodontitis Intrabony defects Enamel matrix derivative Platelet-rich fibrin Periodontal regeneration Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Regenerative periodontal surgery, despite the use of various treatment approaches such as bone grafts, barrier membranes and biologic agents, achieving complete and predictable periodontal regeneration remains a significant clinical challenge. Among biologic agents, enamel matrix derivative (EMD), particularly Emdogain® is one of the most extensively studied and most predictable material. Numerous in vitro studies have evaluated the effects of EMD on osteoblasts and periodontal fibroblasts. These studies indicate that EMD promotes the proliferation of PDL fibroblasts, enhances their protein synthesis, and supports the formation of mineralized nodules. While specific signaling molecules such as IGF-1, IGF-2, PDGF-BB, TNF, TGF-β, and IL-1β have not been directly identified within EMD, the extract appears to foster mesenchymal cell proliferation by inhibiting epithelial growth and encouraging autocrine growth factor release from periodontal fibroblasts [ 1 , 2 ]. A promising strategy to support periodontal regeneration is the use of platelet concentrates, particularly platelet-rich fibrin (PRF). Nearly 40 randomized clinical trials have investigated its regenerative potential, showing PRF to be particularly effective in soft tissue healing, though its benefits in hard tissue regeneration remain a topic of ongoing debate [ 3 – 9 ]. PRF is known to contain several key growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and insulin-like growth factors (IGFs). TGF-β plays a dual role: it stimulates the production of extracellular matrix proteins such as collagen and fibronectin by osteoblasts and fibroblasts, while also exerting anti-inflammatory effects [ 9 ]. PDGF regulates mesenchymal cell proliferation, migration, and survival, whereas IGFs help prevent apoptosis and promote cell proliferation and differentiation [ 10 ]. These growth factors are released more gradually from PRF than from platelet-rich plasma (PRP), which may enhance its therapeutic effects in wound healing. In addition to growth factors, PRF also contains both proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as anti-inflammatory cytokines like interleukin-4 (IL-4) and vascular endothelial growth factor (VEGF) [ 5 , 7 , 11 , 12 ]. The proinflammatory cytokines play a role in the early, proliferative stages of healing, while the anti-inflammatory components help regulate tissue remodeling and angiogenesis. Experimental studies support PRF’s regenerative capabilities. Li et al. demonstrated that PRF enhanced the migration and proliferation of periodontal progenitor cells in vitro, producing effects comparable to those of osteogenic media and superior to platelet-poor plasma [ 13 ]. In animal models, subcutaneous PRF implants integrated with host tissues and were partially replaced by collagen within two weeks. In clinical settings, PRF application has been associated with bone fill in peri-implant defects. Chang et al. proposed that PRF promotes healing of intrabony periodontal defects by upregulating signaling molecules such as phosphorylated extracellular signal-regulated kinase (p-ERK), osteoprotegerin (OPG), and alkaline phosphatase (ALP) in regenerating tissues [ 14 ]. Given the extensive research supporting both PRF and EMD in periodontal regeneration, this randomized clinical trial aims to compare the efficacy of PRF and EMD in the treatment of intrabony periodontal defects. Methods The study protocol follows the recommendations of the CONSORT guidelines[15]. Registration number: NCT07183631. 1.1 Study Design and Patient Selection A total of 30 patients (18 females and 12 males) diagnosed with chronic periodontitis were included in this randomized parallel-design study, with 15 patients assigned to each group after providing informed consent. First evaluation was performed 6 months after surgery. The study adhered to the ethical principles outlined in the Helsinki Declaration of 1983 and 2013[16]. However, only 26 patients (15 females and 11 males) completed the three-year evaluation. Four patients were lost to follow-up due to one participant tooth had to be removed and three relocating (Figure 1). Prior to enrolment, all patients received thorough oral hygiene instructions, as well as full-mouth supra- and subgingival treatment, scaling and root planing using ultrasonic and hand instruments. Subgingival scaling was conducted under local anaesthesia. Three months post-initial therapy, periodontal status was controlled to determine eligibility based on the following inclusion criteria: No systemic conditions affecting treatment outcomes Good oral hygiene [plaque index (PI) <1; gingival index (GI) <1] [17] Compliance with the maintenance program Presence of one intra-bony defect with a probing pocket depth (PPD) of ≥6 mm and an intra-bony component of ≥ 4 mm confirmed by radiographs. Exclusion criteria were the following: (1) significant medical conditions: irradiation in the maxillofacial area, uncontrolled diabetes or hypertension, systemic steroid or bisphosphonate treatment, pregnancy, or lactation, infectious diseases, (2) age 5 cigarettes/day), (4) high residual inflammation (FMBS >25%), (5) poor oral hygiene (FMPS >25%), and (6) defect-related factors: furcation involvement, endo-periodontal defects or multi-tooth defects. Clinical Assessment At study-designated teeth, the following clinical parameters were assessed one week before, at six months, and 3 years post-surgery using a standardized periodontal probe (PCP 12, Hu-Friedy, Chicago, IL, USA): Plaque index (PI) [17] Gingival index (GI) [17] Probing pocket depth (PPD) Gingival recession (GR) Clinical attachment loss (CAL) Bone Sounding (BS) Measurements were recorded at six sites per tooth: mesiovestibular (mv), midvestibular (v), distovestibular (dv), mesiooral (mo), midoral (o), and distooral (do) by a calibrated investigator blinded to the surgical procedure (FN). The cemento-enamel junction (CEJ) was used as the reference point. When the CEJ was not visible, a restoration margin was used. The study reports only measurements at the same, at baseline the deepest point of the selected defects. Baseline and postoperative radiographs were taken using the long-cone paralleling technique. Intra-Examiner Reproducibility To ensure measurement consistency, the examiner was calibrated using five patients, each with ten teeth exhibiting PPD >6 mm on at least one aspect. Patients were evaluated twice, 48 hours apart, and calibration was accepted if baseline and follow-up measurements matched to the millimeter in at least 90% of cases. The examiner remained blinded to the surgical procedures. Randomization procedure Defects were allocated to treatment arms using a randomized block design. Patients were randomly assigned in a 1:1 ratio to either the test group (PRF) or the control group (EMD). Group assignments were concealed in sequentially numbered, opaque, sealed envelopes, which were opened only at the time of surgery. This procedure ensured that neither the patient nor the investigators were aware of the allocation. Statistical analysis Data were expressed as mean ± standard deviation (SD). Normality of distribution was assessed using the Shapiro–Wilk test. For normally distributed variables, comparisons within groups (baseline vs. 6 months, baseline vs. 3 years) and between groups (PRF vs. EMD) were performed using paired and independent Student’s t-tests, respectively. For variables not normally distributed, the Wilcoxon signed-rank test (intragroup comparisons) and Mann–Whitney U test (intergroup comparisons) were applied. A p-value of <0.05 was considered statistically significant. Statistical analyses were performed using (SPSS version XX, IBM Corp., Armonk, NY, USA). Sample size calculation The primary outcome variable was the absolute clinical attachment level (CAL) at 6 months. Based on data from previous clinical studies on the treatment of intrabony periodontal defects, a standard deviation of approximately 2.0 mm for CAL measurements was assumed. With 15 participants per group, a two-sided significance level of α = 0.05 provides 80% power to detect a clinically relevant between-group difference of 2.0 mm in CAL. This sample size was considered appropriate given the feasibility of patient recruitment and the planned long-term follow-up. Surgical Procedures All surgeries were performed under local anesthesia by the same surgeon (F.D.). The surgical treatment involved intracrevicular incisions, raising full-thickness flaps vestibularly and orally without vertical releasing incisions, debridement of granulation tissue, scaling and root planing using hand and ultrasonic instruments. Test Group (PRF Application) Platelet-rich fibrin (PRF) was prepared according to the manufacturer’s instructions. A blood sample was collected from the cubital vein in 10 ml tubes without anticoagulant and centrifuged at 3000 rpm for 10 minutes using a GLO GT416 table centrifuge (GLO Glotech Co. Ltd, Korea) and GLO PRP collection kit (GLO PRP-Kit, Glotech Co, Asan Choong-nam, Korea/ Glofinn, Finland ). Without anticoagulant, platelet activation occurred rapidly, leading to coagulation cascade initiation. The centrifugation process resulted in three layers: Platelet-poor plasma (PPP) (top layer) Fibrin clot (PRF) (middle layer) Red blood cells (RBC) (bottom layer) The fibrin clot (PRF) was extracted and applied directly to the defect in its gel form (Figure 2). Control Group (EMD Application) In the control group, the root surface was conditioned with 24% ethylenediaminetetraacetic acid (EDTA) gel for two minutes, washed with physiological saline solution, dried, and treated with enamel matrix derivative (EMD), (“ Emdogain”, Straumann, Switzerland) per manufacturer recommendations. The flap was then closed with vertical mattress sutures (Figure 3). Postoperative Care All patients received systemic antibiotics (Amoxicillin 1000 mg, twice daily) for one week following surgery. Post-surgical care consisted of 0.2% chlorhexidine rinses twice daily for two weeks and analgesics (Ibuprofen 600 mg, twice daily for three days). Sutures were removed after 14 days. Patients were reviewed monthly during the first six months and at three-month intervals thereafter. During the first six months, no probing or subgingival instrumentation was performed. Recall visits focused on reinforcement of oral hygiene and professional supragingival cleaning. Clinical evaluations were carried out at 6 months and again at the 3-year follow-up. Results Postoperative healing was uneventful. No adverse reactions to antibiotics or analgesics were reported. Patients in both groups expressed high satisfaction with treatment, largely due to the possibility to tooth retention. Baseline patient characteristics, defect distribution and characteristics are presented in Table 1, with no statistically significant differences found between groups. Table 1: Baseline patient, tooth and defect characteristics. Variable PRF group (n=15) EMD group (n=15) Age (years, mean ± SD) 42.2 ± 8.3 45.7 ± 7.9 Gender (M/F) 7 / 8 5 / 10 Smokers 0 0 Tooth type F: 7 / PM: 11 / M: 12 Splinting Yes: 12 / No: 18 Type of bony defects 1-wall: 8 / 2-wall: 16 / 3-wall: 6 Test group At 6 months after therapy, the test group showed a reduction in mean PPD from 8.85±2.27 mm to 4.38±1.95 mm ( p < 0.001) and a change in mean CAL from 10.31±1.75 to 5.92±2.36 mm ( p < 0.001). At three years, mean PPD and CAL measured 5.15±2.03 and 6.53±2.26, respectively. At three years, both PPD and CAL were statistically significantly improved compared with baseline ( p < 0.001) without statistically significant differences between the 6 months and three-year results (Figure 4). After 6 months, the test group showed a reduction in mean GR from 1.46±1.27 to 1.54±1.56 mm ( p < 0.989). At three years, mean GR measured 1.38±1.12 mm without statistically significant differences between the 6 months and three-year results ( p < 0.957). After 6 months, the test group showed significant reduction in mean BS from 10.46 ±2.63 to 6.38±1.66 mm. An elevated BS was detected after three years 7.00±2.24 mm ( p < 0.001) (Figure 4). Although no radiographic evaluation was performed, a stable and well-defined bone fill was visible on the radiographs in all cases (Figure 5). Control group In the control group, after 6 months, mean PPD was reduced from 8.08±2.53 to 4.46±1.27 mm ( p <0.001;) and mean CAL changed from 9.23±2.62 to 7.31±1.49 mm ( p <0.001). At three years, mean PPD and CAL measured 4.77±2.49 and 6.69±2.75 mm, respectively, and were still statistically significantly improved compared with baseline (Figure 6). After 6 months, the control group showed a reduction in mean GR from 1.15±1.34 to 2.85±1.34 mm ( p < 0.001). At three years, mean GR measured 1.92±1.44 mm with not statistically significant differences between the 6 months and three-year results ( p < 0.001). After 6 months, the control group showed significant reduction in mean BS from 9.53±2.54 to 5.92±1.19 mm. At three years an elevated BS measured 7.00±2.48 mm ( p < 0.001) (Figure 6). Although no radiographic evaluation was performed, a stable and well-defined bone fill was visible on the radiographs in all cases (Figure 5). Inter-group analysis The inter-group analysis confirmed comparable outcomes between the two treatment modalities. The test treatment, at 6 months, yielded statistically significantly lower GR than the control one ( p < 0.031). However, after three years there is no statistical difference can be detected in any of the measurement parameters (Figure 7). The intergroup analysis showed no statistically significant differences in PPD, CAL or BS mean values at 6 months and after 3 years too, suggesting that PRF could be considered a reliable alternative for periodontal regenerative therapy (Figure 7). Discussion Periodontal regeneration remains a central challenge in the treatment of advanced periodontitis due to the need for coordinated regeneration of multiple tissues, including cementum, periodontal ligament and alveolar bone. Biologic agents such as EMDs and platelet concentrates like PRF have emerged as promising strategies to enhance regenerative outcomes. In this randomized clinical trial, in both PRF and EMD group a significant clinical improvement can be detected in the treatment of intrabony periodontal defects. Our findings are already evident at six months and remained stable over the three-year follow-up period. Probing pocket depth (PPD) and CAL improved markedly in both groups, with slightly greater early gains in the PRF group, although these differences diminished over time. This pattern mirrors previous reports indicating that PRF may provide an advantage during the initial healing phase, while long-term outcomes tend to converge with those of EMD [ 18 ]. At six months, in PRF-group significantly lower recession can be detected, compared with EMD (1.54 ± 1.56 mm vs. 2.85 ± 1.34 mm, p = 0.031), suggesting a favorable early soft tissue response. Our findings are in line with Aydemir et al., who reported mean GR values of 2.08 ± 0.97 mm after six months in PRF-treated defects, comparable to our observations [ 18 ]. The fibrin matrix of PRF is thought to facilitate fibroblast migration and angiogenesis, accelerating epithelial coverage and minimizing early recession. However, at the three-year follow-up, this difference was no longer apparent (1.38 ± 1.12 mm for PRF vs. 1.92 ± 1.44 mm for EMD), consistent with the view that the early soft tissue advantage of PRF is not sustained over time. In terms of PPD and CAL, there were no statistical significant difference between test and control group at six months. At three years, these improvements were largely maintained, with final PPD values of 5.15 ± 2.03 mm (PRF) and 4.77 ± 2.49 mm (EMD), and CAL values of 6.53 ± 2.26 mm and 6.69 ± 2.75 mm, respectively. These outcomes closely parallel those of Iorio-Siciliano et al., who reported sustained CAL gains of approximately 3 mm in EMD-treated sites after five years [ 19 ]. It is also in line with the findings of meta-analysis showing mean PPD reductions of 3.0-3.5 mm with PRF [ 8 , 20 ]. Taken together, the results confirm that both materials can produce clinically meaningful improvements that are stable over extended periods. Hard tissue changes, assessed by bone sounding, followed a similar trajectory in both groups. At six months, PRF-treated sites improved from 10.46 ± 2.63 mm to 6.38 ± 1.66 mm, while EMD-treated sites improved from 9.53 ± 2.54 mm to 5.92 ± 1.19 mm. At three years, however, BS values in both groups had slightly increased to 7.0 mm, suggesting some remodelling of regenerated tissues. Similar trends have been described in long-term clinical studies by Sculean et al. and Trombelli et al., where initial bone fill was followed by minor adjustments over time [ 2 , 21 ]. These changes likely reflect normal physiological bone remodelling rather than a true relapse of disease, underscoring the importance of long-term follow-up when evaluating regenerative outcomes. Overall, our results indicate that PRF and EMD achieve comparable long-term regenerative outcomes, although their clinical profiles differ in the early postoperative phase. PRF appears to confer a transient soft tissue advantage by limiting gingival recession, while EMD continues to be supported by extensive histological and clinical evidence as the most predictable material for achieving true periodontal regeneration, including the formation of new cementum, periodontal ligament, and alveolar bone [ 11 , 22 , 23 ]. From a clinical perspective, PRF represents a cost-effective and autologous alternative, especially in patients for whom minimizing postoperative recession is a priority or where the use of autologous biomaterials is preferred. Nevertheless, the wealth of histological data supporting EMD underscores its role as the current gold standard in periodontal regeneration. Future research should aim to validate these findings in larger, multi-centre randomized trials with longer follow-ups and advanced three-dimensional imaging techniques such as CBCT. Such studies would help to determine whether the early soft tissue benefits of PRF can translate into distinct long-term advantages and clarify its role relative to EMD in regenerative periodontal therapy. Conclusions Our findings suggest that the autologous PRF represents a viable and cost-effective alternative to EMD for periodontal healing. One noteworthy observation was that PRF demonstrated a short-term advantage in reducing postoperative gingival recession, however long-term outcomes were comparable between the two groups. Future studies with larger populations, human histology and radiographic assessments will further elucidate the regenerative potential of PRF. Declarations Ethical approval and consent to participate: The study was approved by the local ethics committee at Semmelweis University, Budapest, Hungary (SE RKEB: 116/2021). The study was conducted following the Helsinki Declaration. Informed consent to participate was obtained from all participants. Consent for publication: The corresponding author accepts responsibility for releasing this material on behalf of all co-authors. Availability of data and materials: the datasets used in this study can be found in the supplementary material. Competing interests: authors declare no conflict of interest. Funding: no funds to declare. Authors’ contributions: F.D.: Conceptualization, Writing - original draft, Data curation, Investigation, Supervision, Project administration, Surgery F.N.: Data curation, Investigation, Formal analysis N.A.: Data curation, Visualization, Formal analysis, Statistics E.S.: Formal analysis, Methodology, Writing - original draft, Writing - review & editing. All authors reviewed the manuscript. Acknowledgements: not applicable. Abbreviations EMD enamel matrix derivate PRF platelet rich fibrin PPD probing pocket depth GR gingival recesssion CAL clinical attachment loss BS bone sonding p-ERK signal-regulated kinase and OPG osteoprotegerin ALP alkaline phosphatase PDGF platelet derived growth factor TGF-β transforming growth factor beta IGFs insulin like growth factor TNF-α tumor necrosis factor-alpha IL-1β interleukin 1beta IL-6 interleukin 6 IL-4 interleukin 4 VEGF vascular endothelial growth factor PI plaque index FMPS full mouth plaque score GI gingival index Mv mid-vestibular V vestibular Dv disto-vestibular Mo mesio-oral O oral Do disto-oral CEJ cemento-enamel junction SD standard deviation PPP platelet poor plasma PRF platelet rich fibrin RBC red blot clot EDTA ethylenediaminetetraacetic References Sculean A, Blaes A, Arweiler N, Reich E, Donos N, Brecx M: The effect of postsurgical antibiotics on the healing of intrabony defects following treatment with enamel matrix proteins . 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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-9163030","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":628508442,"identity":"20efd7c0-ec73-4434-a7d9-67cae22b7f62","order_by":0,"name":"Ferenc Dőri","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Ferenc","middleName":"","lastName":"Dőri","suffix":""},{"id":628508443,"identity":"8bf68ddf-d599-4c77-9d6e-370a6d3b3a7e","order_by":1,"name":"Florina Németh","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Florina","middleName":"","lastName":"Németh","suffix":""},{"id":628508444,"identity":"ca0dbfbc-2f1c-4d4e-90ff-247e6d544e3e","order_by":2,"name":"Nicole Arweiler","email":"","orcid":"","institution":"University of Marburg","correspondingAuthor":false,"prefix":"","firstName":"Nicole","middleName":"","lastName":"Arweiler","suffix":""},{"id":628508445,"identity":"da9627ff-a821-4749-918e-a2aa1cc9d499","order_by":3,"name":"Eleonora Solyom","email":"data:image/png;base64,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","orcid":"","institution":"Semmelweis University","correspondingAuthor":true,"prefix":"","firstName":"Eleonora","middleName":"","lastName":"Solyom","suffix":""}],"badges":[],"createdAt":"2026-03-18 21:23:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9163030/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9163030/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107948239,"identity":"f7c4fa76-aa20-4746-a216-035db3e23780","added_by":"auto","created_at":"2026-04-28 00:19:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":144547,"visible":true,"origin":"","legend":"\u003cp\u003ePatients follow up according to CONSORT flow-diagram\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/e78eb83fa6d80a09660f69b8.png"},{"id":108006900,"identity":"fc5792b3-a41e-46da-878a-6e148d9b4d11","added_by":"auto","created_at":"2026-04-28 12:57:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":491037,"visible":true,"origin":"","legend":"\u003cp\u003eApplication of PRF to the periodontal bony defects.\u003c/p\u003e\n\u003cp\u003ePRF case: a) preoperative measurements; b) cleaned periodontal defect; c) insertion of the PRF clot; d) sutures; e) clinical picture after three years;\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/041e3920b2436634f3b8c236.png"},{"id":108186815,"identity":"607c80b3-eba9-428b-959c-210895927dbc","added_by":"auto","created_at":"2026-04-30 09:17:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":583373,"visible":true,"origin":"","legend":"\u003cp\u003eApplication of EMD to the periodontal bony defects.\u003c/p\u003e\n\u003cp\u003ea) preoperative measurements; b) cleaned periodontal defect; c) EMD application on the conditioned and dried root surface; d) sutures; e) clinical picture after three years\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/ee94a2d8b4e9baa9eedaa162.png"},{"id":108007645,"identity":"574d229c-5662-4e85-815b-4f6bf1000576","added_by":"auto","created_at":"2026-04-28 13:01:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":336567,"visible":true,"origin":"","legend":"\u003cp\u003ePRF (Test) group: PPD-, GR-, CAL-, BS-values, preoperative, at 6 months, and 3 years\u003cdel\u003e \u003c/del\u003epostoperative.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/c8bc64b29c0dd907c729fc7a.png"},{"id":107948242,"identity":"cb2e4553-44a4-4a32-8ac8-6c144efd479a","added_by":"auto","created_at":"2026-04-28 00:19:32","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":522525,"visible":true,"origin":"","legend":"\u003cp\u003eTest and control case: On the radiographs a stable and well-defined bone fill can be detected. a) preop; b) 6 months postoperatively; c) three years postoperatively.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/92ffef1490ffbc2ebe13fe5c.png"},{"id":108007129,"identity":"44e29f1e-0fd8-48d0-90c0-2d1d4ce5b93d","added_by":"auto","created_at":"2026-04-28 12:58:39","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":327290,"visible":true,"origin":"","legend":"\u003cp\u003eEMD (Control) group: PPD-, GR-, CAL-, BS-values, preoperative, at 6 months, and 3 years\u003cdel\u003e \u003c/del\u003epostoperative.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/c2892c61bb9dfcec8fe2c3a8.png"},{"id":108007521,"identity":"6fbe4bf6-de5f-4fe3-9c41-fdcffb567a02","added_by":"auto","created_at":"2026-04-28 13:00:20","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":490894,"visible":true,"origin":"","legend":"\u003cp\u003eInter-group PPD-, GR-, CAL-, BS-values; preoperative, 6 months, and 3 years differences between the Test and the Control group\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/142cf5cb46e6bbe8af73b521.png"},{"id":109204026,"identity":"6df1af05-0e03-429e-bde2-ebb9d14ea84d","added_by":"auto","created_at":"2026-05-13 14:52:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3808364,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9163030/v1/5aa57049-75f1-45a4-898c-7b296e9801da.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Three-year results of a prospective, controlled clinical study evaluating treatment of intra- bony defects with PRF or EMD- a randomized control trial","fulltext":[{"header":"Background","content":"\u003cp\u003eRegenerative periodontal surgery, despite the use of various treatment approaches such as bone grafts, barrier membranes and biologic agents, achieving complete and predictable periodontal regeneration remains a significant clinical challenge.\u003c/p\u003e \u003cp\u003eAmong biologic agents, enamel matrix derivative (EMD), particularly Emdogain\u0026reg; is one of the most extensively studied and most predictable material. Numerous in vitro studies have evaluated the effects of EMD on osteoblasts and periodontal fibroblasts. These studies indicate that EMD promotes the proliferation of PDL fibroblasts, enhances their protein synthesis, and supports the formation of mineralized nodules. While specific signaling molecules such as IGF-1, IGF-2, PDGF-BB, TNF, TGF-β, and IL-1β have not been directly identified within EMD, the extract appears to foster mesenchymal cell proliferation by inhibiting epithelial growth and encouraging autocrine growth factor release from periodontal fibroblasts [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA promising strategy to support periodontal regeneration is the use of platelet concentrates, particularly platelet-rich fibrin (PRF). Nearly 40 randomized clinical trials have investigated its regenerative potential, showing PRF to be particularly effective in soft tissue healing, though its benefits in hard tissue regeneration remain a topic of ongoing debate [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePRF is known to contain several key growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and insulin-like growth factors (IGFs). TGF-β plays a dual role: it stimulates the production of extracellular matrix proteins such as collagen and fibronectin by osteoblasts and fibroblasts, while also exerting anti-inflammatory effects [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. PDGF regulates mesenchymal cell proliferation, migration, and survival, whereas IGFs help prevent apoptosis and promote cell proliferation and differentiation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These growth factors are released more gradually from PRF than from platelet-rich plasma (PRP), which may enhance its therapeutic effects in wound healing. In addition to growth factors, PRF also contains both proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as anti-inflammatory cytokines like interleukin-4 (IL-4) and vascular endothelial growth factor (VEGF) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The proinflammatory cytokines play a role in the early, proliferative stages of healing, while the anti-inflammatory components help regulate tissue remodeling and angiogenesis. Experimental studies support PRF\u0026rsquo;s regenerative capabilities. Li et al. demonstrated that PRF enhanced the migration and proliferation of periodontal progenitor cells in vitro, producing effects comparable to those of osteogenic media and superior to platelet-poor plasma [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In animal models, subcutaneous PRF implants integrated with host tissues and were partially replaced by collagen within two weeks. In clinical settings, PRF application has been associated with bone fill in peri-implant defects. Chang et al. proposed that PRF promotes healing of intrabony periodontal defects by upregulating signaling molecules such as phosphorylated extracellular signal-regulated kinase (p-ERK), osteoprotegerin (OPG), and alkaline phosphatase (ALP) in regenerating tissues [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the extensive research supporting both PRF and EMD in periodontal regeneration, this randomized clinical trial aims to compare the efficacy of PRF and EMD in the treatment of intrabony periodontal defects.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study protocol follows the recommendations of the CONSORT guidelines[15].\u0026nbsp;Registration number: NCT07183631.\u003c/p\u003e\n\u003ch4\u003e1.1 \u003cem\u003eStudy Design and Patient Selection\u003c/em\u003e\u003c/h4\u003e\n\u003cp\u003eA total of 30 patients (18 females and 12 males) diagnosed with chronic periodontitis were included in this randomized parallel-design study, with 15 patients assigned to each group after providing informed consent. First evaluation was performed 6 months after surgery.\u0026nbsp;The study adhered to the ethical principles outlined in the Helsinki Declaration of 1983 and 2013[16]. However, only 26 patients (15 females and 11 males) completed the three-year evaluation. Four patients were lost to follow-up due to one participant tooth had to be removed and three relocating (Figure 1).\u003c/p\u003e\n\u003cp\u003ePrior to enrolment, all patients received thorough oral hygiene instructions, as well as full-mouth supra- and subgingival treatment, scaling and root planing using ultrasonic and hand instruments. Subgingival scaling was conducted under local anaesthesia. Three months post-initial therapy, periodontal status was controlled to determine eligibility based on the following inclusion criteria:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eNo systemic conditions affecting treatment outcomes\u003c/li\u003e\n \u003cli\u003eGood oral hygiene [plaque index (PI) \u0026lt;1; gingival index (GI) \u0026lt;1] [17]\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCompliance with the maintenance program\u003c/li\u003e\n \u003cli\u003ePresence of one intra-bony defect with a probing pocket depth (PPD) of \u0026ge;6 mm and an intra-bony component of \u0026ge; 4 mm confirmed by radiographs. \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eExclusion criteria were the following: (1) significant medical conditions: irradiation in the maxillofacial area, uncontrolled diabetes or hypertension, systemic steroid or bisphosphonate treatment, pregnancy, or lactation, infectious diseases, (2) age \u0026lt;18 years, (3) smokers (\u0026gt;5 cigarettes/day), (4) high residual inflammation (FMBS \u0026gt;25%), (5) poor oral hygiene (FMPS \u0026gt;25%), and (6) defect-related factors: furcation involvement, endo-periodontal defects or multi-tooth defects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical Assessment\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt study-designated teeth, the following clinical parameters were assessed one week before, at six months, and 3 years post-surgery using a standardized periodontal probe (PCP 12, Hu-Friedy, Chicago, IL, USA):\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003ePlaque index (PI) [17]\u003c/li\u003e\n \u003cli\u003eGingival index (GI) [17]\u003c/li\u003e\n \u003cli\u003eProbing pocket depth (PPD)\u003c/li\u003e\n \u003cli\u003eGingival recession (GR)\u003c/li\u003e\n \u003cli\u003eClinical attachment loss (CAL)\u003c/li\u003e\n \u003cli\u003eBone Sounding (BS)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eMeasurements were recorded at six sites per tooth: mesiovestibular (mv), midvestibular (v), distovestibular (dv), mesiooral (mo), midoral (o), and distooral (do) by a calibrated investigator blinded to the surgical procedure (FN). The cemento-enamel junction (CEJ) was used as the reference point. When the CEJ was not visible, a restoration margin was used. The study reports only measurements at the same, at baseline the deepest point of the selected defects. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Baseline and postoperative radiographs were taken using the long-cone paralleling technique.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIntra-Examiner Reproducibility\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTo ensure measurement consistency, the examiner was calibrated using five patients, each with ten teeth exhibiting PPD \u0026gt;6 mm on at least one aspect. Patients were evaluated twice, 48 hours apart, and calibration was accepted if baseline and follow-up measurements matched to the millimeter in at least 90% of cases. The examiner remained blinded to the surgical procedures.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRandomization procedure\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDefects were allocated to treatment arms using a randomized block design. Patients were randomly assigned in a 1:1 ratio to either the test group (PRF) or the control group (EMD). Group assignments were concealed in sequentially numbered, opaque, sealed envelopes, which were opened only at the time of surgery. This procedure ensured that neither the patient nor the investigators were aware of the allocation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Statistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as mean \u0026plusmn; standard deviation (SD). Normality of distribution was assessed using the Shapiro\u0026ndash;Wilk test. For normally distributed variables, comparisons within groups (baseline vs. 6 months, baseline vs. 3 years) and between groups (PRF vs. EMD) were performed using paired and independent Student\u0026rsquo;s t-tests, respectively. For variables not normally distributed, the Wilcoxon signed-rank test (intragroup comparisons) and Mann\u0026ndash;Whitney U test (intergroup comparisons) were applied. A p-value of \u0026lt;0.05 was considered statistically significant. Statistical analyses were performed using (SPSS version XX, IBM Corp., Armonk, NY, USA).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSample size calculation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome variable was the absolute clinical attachment level (CAL) at 6 months. Based on data from previous clinical studies on the treatment of intrabony periodontal defects, a standard deviation of approximately 2.0 mm for CAL measurements was assumed. With 15 participants per group, a two-sided significance level of \u0026alpha; = 0.05 provides 80% power to detect a clinically relevant between-group difference of 2.0 mm in CAL. This sample size was considered appropriate given the feasibility of patient recruitment and the planned long-term follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSurgical Procedures\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll surgeries were performed under local anesthesia by the same surgeon (F.D.). The surgical treatment involved intracrevicular incisions, raising full-thickness flaps vestibularly and orally without vertical releasing incisions, debridement of granulation tissue, scaling and root planing using hand and ultrasonic instruments.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTest Group (PRF Application)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePlatelet-rich fibrin (PRF) was prepared according to the manufacturer\u0026rsquo;s instructions. A blood sample was collected from the cubital vein in 10 ml tubes without anticoagulant and centrifuged at 3000 rpm for 10 minutes using a GLO GT416 table centrifuge \u003cem\u003e(GLO Glotech Co. Ltd, Korea)\u003c/em\u003e and GLO PRP collection kit \u003cem\u003e(GLO PRP-Kit,\u003c/em\u003e \u003cem\u003eGlotech Co, Asan Choong-nam, Korea/ Glofinn, Finland\u003c/em\u003e).\u0026nbsp;Without anticoagulant, platelet activation occurred rapidly, leading to coagulation cascade initiation. The centrifugation process resulted in three layers:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003ePlatelet-poor plasma (PPP) (top layer)\u003c/li\u003e\n \u003cli\u003eFibrin clot (PRF) (middle layer)\u003c/li\u003e\n \u003cli\u003eRed blood cells (RBC) (bottom layer)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe fibrin clot (PRF) was extracted and applied directly to the defect in its gel form\u0026nbsp;(Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003c/em\u003e\u003c/strong\u003e\u003cem\u003eControl Group (EMD Application)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the control group, the root surface was conditioned with 24% ethylenediaminetetraacetic acid (EDTA) gel for two minutes, washed with physiological saline solution, dried, and treated with enamel matrix derivative (EMD), (\u0026ldquo;\u003cem\u003eEmdogain\u0026rdquo;, Straumann, Switzerland)\u003c/em\u003e per manufacturer recommendations. The flap was then closed with vertical mattress sutures (Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePostoperative Care\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll patients received systemic antibiotics (Amoxicillin 1000 mg, twice daily) for one week following surgery. Post-surgical care consisted of 0.2% chlorhexidine rinses twice daily for two weeks and analgesics (Ibuprofen 600 mg, twice daily for three days). Sutures were removed after 14 days.\u003c/p\u003e\n\u003cp\u003ePatients were reviewed monthly during the first six months and at three-month intervals thereafter. During the first six months, no probing or subgingival instrumentation was performed. Recall visits focused on reinforcement of oral hygiene and professional supragingival cleaning. Clinical evaluations were carried out at 6 months and again at the 3-year follow-up.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePostoperative healing was uneventful. No adverse reactions to antibiotics or analgesics were reported. Patients in both groups expressed high satisfaction with treatment, largely due to the possibility to tooth retention.\u003c/p\u003e\n\u003cp\u003eBaseline patient characteristics, defect distribution and characteristics are presented in Table 1, with no statistically significant differences found between groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eBaseline patient, tooth and defect characteristics.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"556\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eVariable\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePRF group (n=15)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eEMD group (n=15)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eAge (years, mean \u0026plusmn; SD)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e42.2 \u0026plusmn; 8.3\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e45.7 \u0026plusmn; 7.9\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eGender (M/F)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e7 / 8\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e5 / 10\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSmokers\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTooth type\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eF: 7 / PM: 11 / M: 12\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSplinting\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eYes: 12 / No: 18\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eType of bony defects\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e1-wall: 8 / 2-wall: 16 / 3-wall: 6\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTest group\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt 6 months after therapy, the test group showed a reduction in mean PPD from 8.85\u0026plusmn;2.27 mm to 4.38\u0026plusmn;1.95 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001) and a change in mean CAL from 10.31\u0026plusmn;1.75 to 5.92\u0026plusmn;2.36 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). At three years, mean PPD and CAL measured 5.15\u0026plusmn;2.03 and 6.53\u0026plusmn;2.26, respectively. At three years, both PPD and CAL were statistically significantly improved compared with baseline (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001) without statistically significant differences between the 6 months and three-year results (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter 6 months, the test group showed a reduction in mean GR from 1.46\u0026plusmn;1.27 to 1.54\u0026plusmn;1.56 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.989). At three years, mean GR measured 1.38\u0026plusmn;1.12 mm without statistically significant differences between the 6 months and three-year results (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.957). \u0026nbsp;After 6 months, the test group showed significant reduction in mean BS from 10.46 \u0026plusmn;2.63 to 6.38\u0026plusmn;1.66 mm. An elevated BS was detected after three years 7.00\u0026plusmn;2.24 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001) (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough no radiographic evaluation was performed, a stable and well-defined bone fill was visible on the radiographs in all cases (Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eControl group\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the control group, after 6 months, mean PPD was reduced from 8.08\u0026plusmn;2.53 to 4.46\u0026plusmn;1.27 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001;) and mean CAL changed from 9.23\u0026plusmn;2.62 to 7.31\u0026plusmn;1.49 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). At three years, mean PPD and CAL measured 4.77\u0026plusmn;2.49 and 6.69\u0026plusmn;2.75 mm, respectively, and were still statistically significantly improved compared with baseline (Figure 6).\u003c/p\u003e\n\u003cp\u003eAfter 6 months, the control group showed a reduction in mean GR from 1.15\u0026plusmn;1.34 to 2.85\u0026plusmn;1.34 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). At three years, mean GR measured 1.92\u0026plusmn;1.44 mm with not statistically significant differences between the 6 months and three-year results (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). After 6 months, the control group showed significant reduction in mean BS from 9.53\u0026plusmn;2.54 to 5.92\u0026plusmn;1.19 mm. At three years an elevated BS measured 7.00\u0026plusmn;2.48 mm (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001) (Figure 6).\u003c/p\u003e\n\u003cp\u003eAlthough no radiographic evaluation was performed, a stable and well-defined bone fill was visible on the radiographs in all cases (Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInter-group analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe inter-group analysis confirmed comparable outcomes between the two treatment modalities.\u0026nbsp;The test treatment, at 6 months, yielded statistically significantly lower GR than the control one (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.031). However, after three years there is no statistical difference can be detected in any of the measurement parameters (Figure 7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe intergroup analysis showed no statistically significant differences in PPD, CAL or BS mean values at 6 months and after 3 years too, suggesting that PRF could be considered a reliable alternative for periodontal regenerative therapy (Figure 7).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePeriodontal regeneration remains a central challenge in the treatment of advanced periodontitis due to the need for coordinated regeneration of multiple tissues, including cementum, periodontal ligament and alveolar bone. Biologic agents such as EMDs and platelet concentrates like PRF have emerged as promising strategies to enhance regenerative outcomes.\u003c/p\u003e \u003cp\u003eIn this randomized clinical trial, in both PRF and EMD group a significant clinical improvement can be detected in the treatment of intrabony periodontal defects. Our findings are already evident at six months and remained stable over the three-year follow-up period. Probing pocket depth (PPD) and CAL improved markedly in both groups, with slightly greater early gains in the PRF group, although these differences diminished over time. This pattern mirrors previous reports indicating that PRF may provide an advantage during the initial healing phase, while long-term outcomes tend to converge with those of EMD [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt six months, in PRF-group significantly lower recession can be detected, compared with EMD (1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56 mm vs. 2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34 mm, p\u0026thinsp;=\u0026thinsp;0.031), suggesting a favorable early soft tissue response. Our findings are in line with Aydemir et al., who reported mean GR values of 2.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97 mm after six months in PRF-treated defects, comparable to our observations [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The fibrin matrix of PRF is thought to facilitate fibroblast migration and angiogenesis, accelerating epithelial coverage and minimizing early recession. However, at the three-year follow-up, this difference was no longer apparent (1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 mm for PRF vs. 1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44 mm for EMD), consistent with the view that the early soft tissue advantage of PRF is not sustained over time.\u003c/p\u003e \u003cp\u003eIn terms of PPD and CAL, there were no statistical significant difference between test and control group at six months. At three years, these improvements were largely maintained, with final PPD values of 5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03 mm (PRF) and 4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49 mm (EMD), and CAL values of 6.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26 mm and 6.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75 mm, respectively. These outcomes closely parallel those of Iorio-Siciliano et al., who reported sustained CAL gains of approximately 3 mm in EMD-treated sites after five years [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It is also in line with the findings of meta-analysis showing mean PPD reductions of 3.0-3.5 mm with PRF [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Taken together, the results confirm that both materials can produce clinically meaningful improvements that are stable over extended periods.\u003c/p\u003e \u003cp\u003eHard tissue changes, assessed by bone sounding, followed a similar trajectory in both groups. At six months, PRF-treated sites improved from 10.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63 mm to 6.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66 mm, while EMD-treated sites improved from 9.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54 mm to 5.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19 mm. At three years, however, BS values in both groups had slightly increased to 7.0 mm, suggesting some remodelling of regenerated tissues. Similar trends have been described in long-term clinical studies by Sculean et al. and Trombelli et al., where initial bone fill was followed by minor adjustments over time [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These changes likely reflect normal physiological bone remodelling rather than a true relapse of disease, underscoring the importance of long-term follow-up when evaluating regenerative outcomes.\u003c/p\u003e \u003cp\u003eOverall, our results indicate that PRF and EMD achieve comparable long-term regenerative outcomes, although their clinical profiles differ in the early postoperative phase. PRF appears to confer a transient soft tissue advantage by limiting gingival recession, while EMD continues to be supported by extensive histological and clinical evidence as the most predictable material for achieving true periodontal regeneration, including the formation of new cementum, periodontal ligament, and alveolar bone [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. From a clinical perspective, PRF represents a cost-effective and autologous alternative, especially in patients for whom minimizing postoperative recession is a priority or where the use of autologous biomaterials is preferred. Nevertheless, the wealth of histological data supporting EMD underscores its role as the current gold standard in periodontal regeneration.\u003c/p\u003e \u003cp\u003eFuture research should aim to validate these findings in larger, multi-centre randomized trials with longer follow-ups and advanced three-dimensional imaging techniques such as CBCT. Such studies would help to determine whether the early soft tissue benefits of PRF can translate into distinct long-term advantages and clarify its role relative to EMD in regenerative periodontal therapy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings suggest that the autologous PRF represents a viable and cost-effective alternative to EMD for periodontal healing. One noteworthy observation was that PRF demonstrated a short-term advantage in reducing postoperative gingival recession, however long-term outcomes were comparable between the two groups. Future studies with larger populations, human histology and radiographic assessments will further elucidate the regenerative potential of PRF.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u003c/strong\u003e The study was\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eapproved by the local ethics committee at Semmelweis University, Budapest, Hungary (SE RKEB: 116/2021). The study was conducted following the Helsinki Declaration. Informed consent to participate was obtained from all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eThe corresponding author accepts responsibility for releasing this material on behalf of all co-authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ethe datasets used in this study can be found in the supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eauthors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e no funds to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF.D.:\u0026nbsp;\u003c/strong\u003eConceptualization, Writing - original draft, Data curation, Investigation, Supervision, \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Project administration, Surgery\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF.N.:\u0026nbsp;\u003c/strong\u003eData curation, Investigation, Formal analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN.A.:\u0026nbsp;\u003c/strong\u003eData curation, Visualization, Formal analysis, Statistics\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE.S.:\u0026nbsp;\u003c/strong\u003eFormal analysis, Methodology, Writing - original draft, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEMD enamel matrix derivate\u003c/p\u003e\n\u003cp\u003ePRF platelet rich fibrin\u003c/p\u003e\n\u003cp\u003ePPD probing pocket depth\u003c/p\u003e\n\u003cp\u003eGR gingival recesssion\u003c/p\u003e\n\u003cp\u003eCAL clinical attachment loss\u003c/p\u003e\n\u003cp\u003eBS bone sonding\u003c/p\u003e\n\u003cp\u003ep-ERK signal-regulated kinase and \u003c/p\u003e\n\u003cp\u003eOPG osteoprotegerin\u003c/p\u003e\n\u003cp\u003eALP alkaline phosphatase \u003c/p\u003e\n\u003cp\u003ePDGF platelet derived growth factor\u003c/p\u003e\n\u003cp\u003eTGF-\u0026beta; transforming growth factor beta \u003c/p\u003e\n\u003cp\u003eIGFs insulin like growth factor\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha; tumor necrosis factor-alpha \u003c/p\u003e\n\u003cp\u003eIL-1\u0026beta; interleukin 1beta \u003c/p\u003e\n\u003cp\u003eIL-6 interleukin 6\u003c/p\u003e\n\u003cp\u003eIL-4 interleukin 4\u003c/p\u003e\n\u003cp\u003eVEGF vascular endothelial growth factor\u003c/p\u003e\n\u003cp\u003ePI plaque index\u003c/p\u003e\n\u003cp\u003eFMPS full mouth plaque score\u003c/p\u003e\n\u003cp\u003eGI gingival index\u003c/p\u003e\n\u003cp\u003eMv mid-vestibular\u003c/p\u003e\n\u003cp\u003eV vestibular\u003c/p\u003e\n\u003cp\u003eDv disto-vestibular\u003c/p\u003e\n\u003cp\u003eMo mesio-oral\u003c/p\u003e\n\u003cp\u003eO oral\u003c/p\u003e\n\u003cp\u003eDo disto-oral\u003c/p\u003e\n\u003cp\u003eCEJ cemento-enamel junction\u003c/p\u003e\n\u003cp\u003eSD standard deviation\u003c/p\u003e\n\u003cp\u003ePPP platelet poor plasma\u003c/p\u003e\n\u003cp\u003ePRF platelet rich fibrin\u003c/p\u003e\n\u003cp\u003eRBC red blot clot\u003c/p\u003e\n\u003cp\u003eEDTA ethylenediaminetetraacetic \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSculean A, Blaes A, Arweiler N, Reich E, Donos N, Brecx M: \u003cstrong\u003eThe effect of postsurgical antibiotics on the healing of intrabony defects following treatment with enamel matrix proteins\u003c/strong\u003e. \u003cem\u003eJ Periodontol \u003c/em\u003e2001, \u003cstrong\u003e72\u003c/strong\u003e(2):190-195.\u003c/li\u003e\n\u003cli\u003eSculean A, Barb\u0026eacute; G, Chiantella GC, Arweiler NB, Berakdar M, Brecx M: \u003cstrong\u003eClinical evaluation of an enamel matrix protein derivative combined with a bioactive glass for the treatment of intrabony periodontal defects in humans\u003c/strong\u003e. \u003cem\u003eJ Periodontol \u003c/em\u003e2002, \u003cstrong\u003e73\u003c/strong\u003e(4):401-408.\u003c/li\u003e\n\u003cli\u003eSilva FFVe, Chauca-Baja\u0026ntilde;a L, Caponio VCA, Cueva KAS, Velasquez-Ron B, Pad\u0026iacute;n-Iruegas ME, Almeida LL, Lorenzo-Pouso AI, Su\u0026aacute;rez-Pe\u0026ntilde;aranda JM, P\u0026eacute;rez-Say\u0026aacute;ns M: \u003cstrong\u003eRegeneration of periodontal intrabony defects using platelet-rich fibrin (PRF): a systematic review and network meta-analysis\u003c/strong\u003e. \u003cem\u003eOdontology \u003c/em\u003e2024, \u003cstrong\u003e112\u003c/strong\u003e(4):1047-1068.\u003c/li\u003e\n\u003cli\u003eChoukroun J, Diss A, Simonpieri A, Girard M-O, Schoeffler C, Dohan SL, Dohan AJJ, Mouhyi J, Dohan DM: \u003cstrong\u003ePlatelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing\u003c/strong\u003e. \u003cem\u003eOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics \u003c/em\u003e2006, \u003cstrong\u003e101\u003c/strong\u003e(3):e56-e60.\u003c/li\u003e\n\u003cli\u003eDohan Ehrenfest DM, Bielecki T, Jimbo R, Barb\u0026eacute; G, Del Corso M, Inchingolo F, Sammartino G: \u003cstrong\u003eDo the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF)\u003c/strong\u003e. \u003cem\u003eCurr Pharm Biotechnol \u003c/em\u003e2012, \u003cstrong\u003e13\u003c/strong\u003e(7):1145-1152.\u003c/li\u003e\n\u003cli\u003eFujioka-Kobayashi M, Miron RJ, Hernandez M, Kandalam U, Zhang Y, Choukroun J: \u003cstrong\u003eOptimized Platelet-Rich Fibrin With the Low-Speed Concept: Growth Factor Release, Biocompatibility, and Cellular Response\u003c/strong\u003e. \u003cem\u003eJ Periodontol \u003c/em\u003e2017, \u003cstrong\u003e88\u003c/strong\u003e(1):112-121.\u003c/li\u003e\n\u003cli\u003eKobayashi E, Fl\u0026uuml;ckiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, Miron RJ: \u003cstrong\u003eComparative release of growth factors from PRP, PRF, and advanced-PRF\u003c/strong\u003e. \u003cem\u003eClinical Oral Investigations \u003c/em\u003e2016, \u003cstrong\u003e20\u003c/strong\u003e(9):2353-2360.\u003c/li\u003e\n\u003cli\u003eSharma A, Pradeep AR: \u003cstrong\u003eTreatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: a randomized controlled clinical trial\u003c/strong\u003e. \u003cem\u003eJ Periodontol \u003c/em\u003e2011, \u003cstrong\u003e82\u003c/strong\u003e(12):1705-1712.\u003c/li\u003e\n\u003cli\u003eZuleika P, Saleh I, Murti K, Liberty IA, Legiran, Irfanuddin, Surono A: \u003cstrong\u003ePlatelet-rich Fibrin: A Systematic Review of Its Action\u003c/strong\u003e. \u003cem\u003eJournal of Nature and Science of Medicine \u003c/em\u003e2024, \u003cstrong\u003e7\u003c/strong\u003e(4):242-252.\u003c/li\u003e\n\u003cli\u003eSorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U: \u003cstrong\u003eSkin Wound Healing: An Update on the Current Knowledge and Concepts\u003c/strong\u003e. \u003cem\u003eEur Surg Res \u003c/em\u003e2017, \u003cstrong\u003e58\u003c/strong\u003e(1-2):81-94.\u003c/li\u003e\n\u003cli\u003eMiron RJ, Fujioka-Kobayashi M, Bishara M, Zhang Y, Hernandez M, Choukroun J: \u003cstrong\u003ePlatelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review\u003c/strong\u003e. \u003cem\u003eTissue Eng Part B Rev \u003c/em\u003e2017, \u003cstrong\u003e23\u003c/strong\u003e(1):83-99.\u003c/li\u003e\n\u003cli\u003eBaca-Gonzalez L, Serrano Zamora R, Rancan L, Gonz\u0026aacute;lez Fern\u0026aacute;ndez-Tresguerres F, Fern\u0026aacute;ndez-Tresguerres I, L\u0026oacute;pez-Pintor RM, L\u0026oacute;pez-Quiles J, Leco I, Torres J: \u003cstrong\u003ePlasma rich in growth factors (PRGF) and leukocyte-platelet rich fibrin (L-PRF): comparative release of growth factors and biological effect on osteoblasts\u003c/strong\u003e. \u003cem\u003eInternational Journal of Implant Dentistry \u003c/em\u003e2022, \u003cstrong\u003e8\u003c/strong\u003e(1):39.\u003c/li\u003e\n\u003cli\u003eLi Q, Pan S, Dangaria SJ, Gopinathan G, Kolokythas A, Chu S, Geng Y, Zhou Y, Luan X: \u003cstrong\u003ePlatelet-rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation\u003c/strong\u003e. \u003cem\u003eBiomed Res Int \u003c/em\u003e2013, \u003cstrong\u003e2013\u003c/strong\u003e:638043.\u003c/li\u003e\n\u003cli\u003eChang YC, Zhao JH: \u003cstrong\u003eEffects of platelet-rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects\u003c/strong\u003e. \u003cem\u003eAust Dent J \u003c/em\u003e2011, \u003cstrong\u003e56\u003c/strong\u003e(4):365-371.\u003c/li\u003e\n\u003cli\u003eHopewell S, Chan AW, Collins GS, Hr\u0026oacute;bjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eCONSORT 2025 statement: updated guideline for reporting randomised trials\u003c/strong\u003e. \u003cem\u003eBmj \u003c/em\u003e2025, \u003cstrong\u003e389\u003c/strong\u003e:e081123.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eWorld Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects\u003c/strong\u003e. \u003cem\u003eJama \u003c/em\u003e2013, \u003cstrong\u003e310\u003c/strong\u003e(20):2191-2194.\u003c/li\u003e\n\u003cli\u003eL\u0026ouml;e H: \u003cstrong\u003eThe Gingival Index, the Plaque Index and the Retention Index Systems\u003c/strong\u003e. \u003cem\u003eJ Periodontol \u003c/em\u003e1967, \u003cstrong\u003e38\u003c/strong\u003e(6):Suppl:610-616.\u003c/li\u003e\n\u003cli\u003eAydemir Turkal H, Demirer S, Dolgun A, Keceli HG: \u003cstrong\u003eEvaluation of the adjunctive effect of platelet-rich fibrin to enamel matrix derivative in the treatment of intrabony defects. Six-month results of a randomized, split-mouth, controlled clinical study\u003c/strong\u003e. \u003cem\u003eJ Clin Periodontol \u003c/em\u003e2016, \u003cstrong\u003e43\u003c/strong\u003e(11):955-964.\u003c/li\u003e\n\u003cli\u003eIorio-Siciliano V, Blasi A, Nuzzolo P, Matarasso M, Isola G, Ramaglia L: \u003cstrong\u003eTreatment of Periodontal Intrabony Defects Using Enamel Matrix Derivative: Surgical Reentry After an Observation Period of at Least 5 Years\u003c/strong\u003e. \u003cem\u003eInt J Periodontics Restorative Dent \u003c/em\u003e2019, \u003cstrong\u003e39\u003c/strong\u003e(4):537-543.\u003c/li\u003e\n\u003cli\u003eCastro AB, Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, Quirynen M: \u003cstrong\u003eRegenerative potential of leucocyte- and platelet-rich fibrin. Part A: intra-bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eJ Clin Periodontol \u003c/em\u003e2017, \u003cstrong\u003e44\u003c/strong\u003e(1):67-82.\u003c/li\u003e\n\u003cli\u003eTrombelli L, Heitz-Mayfield LJ, Needleman I, Moles D, Scabbia A: \u003cstrong\u003eA systematic review of graft materials and biological agents for periodontal intraosseous defects\u003c/strong\u003e. \u003cem\u003eJ Clin Periodontol \u003c/em\u003e2002, \u003cstrong\u003e29 Suppl 3\u003c/strong\u003e:117-135; discussion 160-112.\u003c/li\u003e\n\u003cli\u003eBosshardt DD: \u003cstrong\u003eBiological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels\u003c/strong\u003e. \u003cem\u003eJournal of Clinical Periodontology \u003c/em\u003e2008, \u003cstrong\u003e35\u003c/strong\u003e(s8):87-105.\u003c/li\u003e\n\u003cli\u003eSculean A, Windisch P, D\u0026ouml;ri F, Keglevich T, Moln\u0026aacute;r B, Gera I: \u003cstrong\u003eEmdogain in regenerative periodontal therapy. A review of the literature\u003c/strong\u003e. \u003cem\u003eFogorv Sz \u003c/em\u003e2007, \u003cstrong\u003e100\u003c/strong\u003e(5):220-232, 211-229.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Periodontitis, Intrabony defects, Enamel matrix derivative, Platelet-rich fibrin, Periodontal regeneration","lastPublishedDoi":"10.21203/rs.3.rs-9163030/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9163030/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePeriodontal regeneration of intrabony defects remains clinically challenging. Enamel matrix derivative (EMD) is a well-documented biologic agent, whereas platelet-rich fibrin (PRF) has emerged as a promising autologous alternative. This prospective controlled clinical study aimed to compare the long-term clinical outcomes of PRF and EMD in the treatment of periodontal intrabony defects.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty patients with chronic periodontitis and at least one intrabony defect [probing pocket depth (PPD)\u0026thinsp;\u0026ge;\u0026thinsp;6 mm; intrabony component\u0026thinsp;\u0026ge;\u0026thinsp;3 mm] were randomly assigned to surgery using PRF (test group) or EMD (control group). Clinical parameters, including PPD, gingival recession (GR), clinical attachment level (CAL), and bone sounding (BS), were recorded at baseline, 6 months, and 3 years postoperatively. Appropriate parametric and nonparametric statistical tests were applied (α\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-six patients completed the 3-year follow-up. In the PRF group, mean PPD was reduced from 8.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27 mm to 4.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95 mm at 6 months and measured 5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03 mm at 3 years (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Mean CAL improved from 10.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.75 mm to 5.92\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36 mm at 6 months and remained stable at 6.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26 mm after 3 years (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the EMD group, mean PPD decreased from 8.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53 mm to 4.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27 mm at 6 months and was 4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49 mm at 3 years, while CAL improved from 9.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62 mm to 7.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49 mm and 6.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75 mm, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At 6 months, GR was significantly lower in the PRF group compared with the EMD group (1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56 mm vs. 2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34 mm; p\u0026thinsp;=\u0026thinsp;0.031). No statistically significant intergroup differences were observed for any parameter at 3 years.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePRF and EMD provided comparable and stable long-term clinical improvements after surgical treatment of intrabony periodontal defects. PRF demonstrated a short-term advantage in reducing postoperative gingival recession. Surgery with PRF may represent a reliable autologous alternative to EMD in periodontal therapy.\u003c/p\u003e\u003ch2\u003eTrial Registration:\u003c/h2\u003e \u003cp\u003eThe study was registered on ClinicalTrials.gov, registration number: NCT07183631, registration date:2025.09.14.; retrospectively registered.\u003c/p\u003e","manuscriptTitle":"Three-year results of a prospective, controlled clinical study evaluating treatment of intra- bony defects with PRF or EMD- a randomized control trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 00:19:27","doi":"10.21203/rs.3.rs-9163030/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-07T07:54:26+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"88399940863599175202252663597169548455","date":"2026-05-02T19:36:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T19:24:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28542889187815563161875850880592796497","date":"2026-05-02T18:11:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19171727053700285935941286484944219413","date":"2026-05-02T02:37:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-22T07:01:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22564406596601881258154895913833380137","date":"2026-04-20T05:26:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51560600796904620599518513152211722695","date":"2026-04-18T14:27:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-18T14:22:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-16T14:18:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-03T07:08:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-31T16:58:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2026-03-31T16:54:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4fec2a2c-18a0-46da-a591-79f7df48b3bb","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-07T07:54:26+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"88399940863599175202252663597169548455","date":"2026-05-02T19:36:38+00:00","index":169,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T19:24:38+00:00","index":168,"fulltext":""},{"type":"reviewerAgreed","content":"28542889187815563161875850880592796497","date":"2026-05-02T18:11:24+00:00","index":167,"fulltext":""},{"type":"reviewerAgreed","content":"19171727053700285935941286484944219413","date":"2026-05-02T02:37:15+00:00","index":162,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T18:54:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 00:19:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9163030","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9163030","identity":"rs-9163030","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}