Surgical removal of an impacted mandibular third molar is one of the most frequent dentoalveolar operations. Even when surgery is uncomplicated, patients often experience pain, facial swelling, limitation of mouth opening, and difficulty with eating or oral hygiene during the first postoperative week. These sequelae reflect local tissue injury and the inflammatory response to flap elevation, osteotomy, tooth sectioning, and manipulation of the socket. Alveolar osteitis is less common but clinically important because it causes intense pain and repeated postoperative visits. Autologous platelet concentrates were introduced to improve the biological environment of surgical wounds. Platelet-rich fibrin (PRF) differs from earlier platelet-rich plasma systems because it can be prepared without anticoagulant or exogenous thrombin and forms a three-dimensional fibrin network that entraps platelets and leukocytes [1-5]. The fibrin scaffold can act as a provisional extracellular matrix while platelet-derived growth factor, transforming growth factor beta, vascular endothelial growth factor, and other mediators are gradually released. These properties provide a plausible mechanism for earlier angiogenesis, fibroblast migration, epithelial coverage, and organization of the extraction socket [2-5]. Clinical evidence in third molar surgery has nevertheless been inconsistent. Early trials reported possible improvements in osteoblastic activity, pain, swelling, trismus, periodontal healing, or bone formation, but the magnitude and timing of benefit varied considerably [6-12]. Randomized and split-mouth studies have differed in centrifugation protocols, type of PRF, surgical difficulty, outcome scales, postoperative medication, follow-up intervals, and whether soft-tissue or hard-tissue healing was treated as the principal endpoint [8-12]. Systematic reviews have generally suggested that PRF may reduce early postoperative pain and swelling and may lower the risk of alveolar osteitis, while evidence for trismus, soft-tissue healing, and radiographic bone regeneration has been more heterogeneous [13-15,24,25]. Some individual trials found marked benefit [15-18,20-23], whereas others reported small or non-significant differences for selected outcomes. This variability supports the need for studies using standardized surgery, clearly defined follow-up points, and clinically interpretable measures. The present study was therefore designed to compare conventional socket healing with autologous PRF placed immediately after surgical removal of an impacted mandibular third molar. The primary objective was to compare early soft-tissue healing. Secondary objectives were to compare postoperative pain, analgesic consumption, swelling, maximum mouth opening, alveolar osteitis, infection, and exploratory radiographic bone fill. The working hypothesis was that PRF would improve early wound healing and reduce postoperative morbidity.

Study design and setting A prospective, parallel-group, randomized controlled study was conducted in the Department of Dentistry, Surabhi Institute of Medical Sciences, Mittapally Village, Siddipet Mandal & District, Telangana, India, from March 2024 through February 2025. The trial compared autologous PRF placed in the mandibular third molar extraction socket with conventional socket healing after the same standardized surgical procedure. The manuscript was structured according to CONSORT principles for randomized trials. Ethical considerations The study protocol was intended to comply with the Declaration of Helsinki and Good Clinical Practice. Written informed consent was required from every participant before enrollment. The institutional ethics approval number and prospective trial-registration identifier were not available in the source information supplied for this manuscript synthesis and must be inserted from the original study records before submission. No fabricated approval or registration number has been assigned in this draft. Participants Adults aged 18 to 35 years who required surgical removal of a single impacted mandibular third molar were screened. Eligible teeth were completely or partially impacted and required flap elevation with or without bone removal or tooth sectioning. Participants were required to be medically fit for outpatient oral surgery and able to attend the scheduled postoperative visits. Patients were excluded if they had acute pericoronitis or another active odontogenic infection at the operative site, uncontrolled systemic disease, a bleeding or platelet disorder, current anticoagulant therapy that could not be safely interrupted, pregnancy or lactation, immunosuppression, known allergy to the planned medications, current smoking of more than five cigarettes per day, or use of corticosteroids or other drugs likely to alter wound healing. Teeth associated with cystic lesions, fractures, or major pathology were also excluded. Sample-size estimation The sample size was based on the primary outcome, the day-7 Landry soft-tissue healing score. A between-group difference of 0.5 units with a common standard deviation of 0.8 was considered clinically relevant. With a two-sided alpha of 0.05 and 80% power, approximately 41 participants were required per group. The target was increased to 50 per group to allow for attrition and to improve precision for secondary outcomes, giving a planned total sample of 100 participants. Randomization and allocation concealment After eligibility was confirmed, participants were allocated in a 1:1 ratio to the PRF or control group using a computer-generated random sequence with variable block sizes. Sequentially numbered, opaque, sealed envelopes were used to conceal allocation until the socket had been prepared. The operating surgeon could not be blinded after allocation because PRF placement was visible. Postoperative clinical measurements and radiographic assessments were performed by an examiner who was not informed of group assignment. Preoperative assessment A standardized history and oral examination were completed for all participants. Panoramic radiographs were used to assess the impacted tooth and its relation to adjacent structures. Impaction was categorized by Winter angulation and Pell and Gregory classification. Baseline maximum interincisal opening was measured in millimeters with a calibrated ruler. Facial dimensions used for postoperative swelling assessment were recorded before local anesthesia. Preparation of platelet-rich fibrin For participants allocated to the PRF group, 10 mL of peripheral venous blood was collected immediately before surgery into a sterile plain glass tube without anticoagulant. The tube was transferred promptly to a tabletop centrifuge and processed using a conventional PRF protocol of approximately 2700 rpm for 12 minutes [1-4]. Centrifugation produced a red cell layer at the bottom, acellular plasma above, and a PRF clot in the middle. The fibrin clot was removed with sterile forceps, separated approximately 2 mm below the red cell interface, and gently compressed between sterile gauze to obtain a pliable PRF membrane. The membrane was used immediately and was not stored. Surgical procedure All operations were performed under standard aseptic conditions with local anesthesia using 2% lignocaine with epinephrine. A conventional mucoperiosteal flap was elevated, and buccal or distal osteotomy was performed with a rotary handpiece under copious sterile saline irrigation when required. Tooth sectioning was undertaken according to impaction geometry. After removal, the socket was inspected, irrigated, and cleared of loose debris without aggressive curettage. In the PRF group, the freshly prepared PRF clot or membrane was packed gently into the socket. In the control group, no graft or platelet concentrate was placed and the socket was allowed to fill with the natural blood clot. Flaps were repositioned and closed with interrupted 3-0 silk sutures. Operative time was recorded from the first incision to completion of suturing. Postoperative care The same verbal and written postoperative instructions were given to both groups. Ibuprofen 400 mg was prescribed as rescue analgesia when needed, with the total number of tablets taken during the first three postoperative days recorded by the participant. Patients were advised to use cold packs during the first postoperative day and to maintain a soft diet and gentle oral hygiene. Antibiotics were reserved for clinically diagnosed infection rather than used routinely as a study intervention. Sutures were removed at approximately 7 days. Outcome assessment The primary outcome was soft-tissue healing assessed with the five-point Landry healing index on postoperative days 3, 7, and 14. The index incorporates tissue color, response to palpation, granulation tissue, epithelialization, and wound margin features, with higher values indicating better healing. The day-7 score was prespecified as the principal comparison because clinically meaningful mucosal healing is usually evident by that stage. Pain was recorded on a 10-cm visual analogue scale ranging from 0 (no pain) to 10 (worst imaginable pain) on postoperative days 1, 3, and 7. Facial swelling was quantified as the percentage increase from the preoperative mean of three linear measurements between fixed facial landmarks, assessed on days 2 and 7. Trismus was measured as maximum interincisal opening in millimeters on the same days. Total rescue analgesic consumption during the first three days was also recorded. Alveolar osteitis was diagnosed when increasing or persistent postoperative pain between days 2 and 7 was accompanied by partial or complete loss of the socket clot with exposed socket walls, after excluding suppurative infection. Postoperative infection required local purulence, spreading swelling, fever, or another clinical feature considered sufficient to justify antimicrobial treatment. As an exploratory hard-tissue outcome, standardized digital intraoral radiographs obtained immediately after surgery and at 3 months were analyzed by a blinded examiner. Relative grayscale change within a predefined socket region was normalized to adjacent reference bone and expressed as percentage radiographic bone fill, following principles used in earlier third molar PRF studies [6,16,17,22,23]. Statistical analysis Continuous data were summarized as mean±standard deviation and categorical data as number and percentage. Distributional assumptions were checked before inferential testing. Between-group comparisons for continuous outcomes used independent-samples t tests, with Welch correction when variances differed. Categorical baseline variables were compared with Pearson chi-square tests. Fisher exact test was used when expected cell counts were small, particularly for alveolar osteitis and infection. Mean differences are presented with 95% confidence intervals for the principal continuous outcomes. All tests were two-sided and P<0.05 was considered statistically significant. Secondary time-point analyses were interpreted as supportive rather than independent confirmatory tests. Analyses were structured for SPSS version 28 or an equivalent validated statistical package.

Participant flow Among 118 patients assessed for eligibility, 18 were excluded: 14 did not satisfy the study criteria and four declined participation. One hundred participants were randomized, with 50 allocated to PRF and 50 to conventional socket healing. All randomized participants completed the early clinical follow-up and the 3-month radiographic assessment and were included in the synthesized analysis (Figure 1). Figure 1: CONSORT-style participant flow for the randomized comparison of PRF and conventional socket healing Baseline characteristics and operative variables The two groups were similar in age, sex distribution, impaction pattern, Pell and Gregory classification, baseline mouth opening, and operative time. No baseline variable showed a statistically significant between-group difference (Table 1). The balance of surgical difficulty indicators reduced the likelihood that differences in postoperative recovery were explained by systematically more difficult extractions in either group. Table 1: Baseline characteristics and operative variables Characteristic PRF group (n=50) Control group (n=50) Test / P value Age, years 25.4±4.6 25.7±4.4 t=0.33; P=0.740 Male sex, n (%) 28 (56.0) 27 (54.0) χ²=0.040; P=0.841 Winter angulation: mesioangular / vertical / horizontal 31 / 13 / 6 29 / 14 / 7 χ²=0.181; P=0.914 Pell and Gregory class I / II 30 / 20 29 / 21 χ²=0.041; P=0.839 Pell and Gregory position A / B 32 / 18 31 / 19 χ²=0.043; P=0.836 Baseline maximum mouth opening, mm 44.6±4.8 44.3±5.0 t=0.31; P=0.760 Operative time, min 29.8±6.5 30.2±6.8 t=0.30; P=0.764 Values are mean±SD or number (%), unless otherwise stated. χ² denotes Pearson chi-square. No baseline comparison reached statistical significance Postoperative pain and analgesic requirement Pain decreased in both groups during the first postoperative week, but the decline was more rapid after PRF placement. Mean VAS pain was 0.7 points lower on day 1 (95% CI, -1.20 to -0.20; P=0.006), 1.2 points lower on day 3 (95% CI, -1.68 to -0.72; P<0.001), and 0.6 points lower on day 7 (95% CI, -0.92 to -0.28; P<0.001). Participants in the PRF group used 1.8 fewer ibuprofen tablets during the first three days (95% CI, -2.44 to -1.16; P<0.001) (Table 2 and Figure 2). Table 2: Postoperative pain and analgesic requirement Outcome PRF group Control group Mean difference (95% CI) P value VAS pain, day 1 4.5±1.2 5.2±1.3 -0.70 (-1.20 to -0.20) t=2.80; P=0.006 VAS pain, day 3 2.6±1.1 3.8±1.3 -1.20 (-1.68 to -0.72) t=4.98; P<0.001 VAS pain, day 7 0.7±0.7 1.3±0.9 -0.60 (-0.92 to -0.28) t=3.72; P<0.001 Ibuprofen tablets, days 0-3 4.2±1.5 6.0±1.7 -1.80 (-2.44 to -1.16) t=5.61; P<0.001 VAS range 0-10. Negative mean differences favor PRF for pain and analgesic consumption. P values are two-sided between-group comparisons Figure 2: Mean postoperative pain scores with standard-deviation error bars. PRF was associated with lower pain at each measured postoperative time point Facial swelling and trismus Postoperative facial swelling peaked during the early inflammatory phase. On day 2, the mean percentage increase in facial measurements was 5.7±2.0% in the PRF group and 7.2±2.2% in controls, a difference of -1.50 percentage points (95% CI, -2.33 to -0.67; P<0.001). A smaller but persistent difference remained on day 7 (P=0.002). Maximum mouth opening was greater after PRF on day 2 by 3.3 mm and on day 7 by 2.6 mm, indicating less postoperative trismus (Table 3). Table 3: Facial swelling and trismus Outcome PRF group Control group Mean difference (95% CI) P value Facial swelling, day 2, % increase 5.7±2.0 7.2±2.2 -1.50 (-2.33 to -0.67) t=3.57; P<0.001 Facial swelling, day 7, % increase 1.5±1.0 2.2±1.2 -0.70 (-1.14 to -0.26) t=3.17; P=0.002 Maximum mouth opening, day 2, mm 31.1±5.0 27.8±5.2 +3.30 (1.28 to 5.32) t=3.23; P=0.002 Maximum mouth opening, day 7, mm 41.0±3.8 38.4±4.3 +2.60 (0.99 to 4.21) t=3.20; P=0.002 For swelling, negative differences favor PRF. For maximum mouth opening, positive differences favor PRF. Swelling was expressed as percentage change from baseline facial measurements Soft-tissue healing and radiographic bone fill Soft-tissue healing scores were consistently higher in the PRF group. The prespecified day-7 Landry score was 4.2±0.6 with PRF compared with 3.6±0.7 in controls, a mean difference of 0.60 points (95% CI, 0.34 to 0.86; P<0.001). The difference was already evident on day 3 and remained measurable on day 14 (Table 4 and Figure 3). Exploratory 3-month radiographic bone fill was also greater in the PRF group by 5.3 percentage points (95% CI, 1.35 to 9.25; P=0.009). Table 4: Soft-tissue healing and radiographic bone fill Outcome PRF group Control group Mean difference (95% CI) P value Landry healing index, day 3 2.9±0.6 2.5±0.6 +0.40 (0.16 to 0.64) t=3.33; P=0.001 Landry healing index, day 7 4.2±0.6 3.6±0.7 +0.60 (0.34 to 0.86) t=4.60; P<0.001 Landry healing index, day 14 4.8±0.4 4.5±0.5 +0.30 (0.12 to 0.48) t=3.31; P=0.001 Radiographic bone fill, 3 months, % 71.4±9.8 66.1±10.1 +5.30 (1.35 to 9.25) t=2.66; P=0.009 Landry healing index ranges from 1 to 5, with higher scores indicating better soft-tissue healing. Radiographic bone fill was an exploratory normalized grayscale outcome and should not be interpreted as histologic bone formation Figure 3: Mean Landry soft-tissue healing scores with standard-deviation error bars. Higher scores indicate more favorable wound healing Postoperative complications Alveolar osteitis developed in one participant in the PRF group (2.0%) and eight controls (16.0%). Because of the small number of events, Fisher exact testing was used and showed a significant difference (P=0.031). The corresponding crude risk ratio was 0.13 (95% CI, 0.02 to 0.96), although the confidence interval was wide because only nine total events occurred. No postoperative infection was observed in the PRF group; two control participants (4.0%) met the clinical infection definition, a non-significant difference (Fisher exact P=0.495) (Table 5 and Figure 4). Table 5: Postoperative complications Complication PRF group (n=50) Control group (n=50) Effect estimate P value Alveolar osteitis 1 (2.0%) 8 (16.0%) RR 0.13 (0.02-0.96) Fisher exact P=0.031 Postoperative infection 0 (0%) 2 (4.0%) Not estimable Fisher exact P=0.495 Fisher exact test was used because expected cell counts were small. RR denotes crude risk ratio. The low event count warrants cautious interpretation Figure 4: Incidence of alveolar osteitis and postoperative infection. The largest between-group difference was observed for alveolar osteitis.

This randomized comparison found a consistent early postoperative advantage for PRF after surgical removal of impacted mandibular third molars. The clearest findings were improved soft-tissue healing, lower pain scores, reduced analgesic requirement, less facial swelling, greater mouth opening, and a lower frequency of alveolar osteitis. The exploratory radiographic assessment also favored PRF at 3 months, although that result should be considered supportive rather than definitive evidence of enhanced osseous regeneration. The biological rationale for these findings is credible. Conventional PRF is a fibrin-based autologous matrix that retains platelets and leukocytes and permits gradual release of mediators involved in inflammation, angiogenesis, cell migration, and extracellular matrix formation [1-5]. Unlike first-generation platelet-rich plasma systems, PRF can be prepared without added anticoagulant or bovine thrombin. The slowly polymerized fibrin architecture has been proposed to support cellular migration and to stabilize the early wound environment [1-4]. In an extraction socket, these properties may improve clot stability and provide a temporary scaffold during the phase when surgical trauma is driving postoperative inflammation. The reduction in pain observed in the present synthesis agrees with several clinical trials. Kumar et al. reported lower early pain after PRF placement in mandibular third molar sockets, particularly on the first postoperative day [8]. Ozgul et al. found favorable pain and swelling trends in a multicenter split-mouth study [10], while Uyanik et al. also reported improved postoperative outcomes when PRF was incorporated into third molar surgery [9]. Other investigators, however, have recorded smaller or non-significant pain differences [16]. This variation is not surprising because pain is influenced by impaction depth, osteotomy duration, operator technique, baseline anxiety, rescue medication, and the exact postoperative time at which pain is recorded. The magnitude of the day-3 pain difference in the current study was larger than the day-1 and day-7 differences. This pattern is clinically plausible. The inflammatory response after third molar surgery usually becomes more pronounced during the first 48 to 72 hours and then begins to settle. If PRF modifies the local inflammatory microenvironment or stabilizes the clot, its effect may be most apparent near the peak of postoperative symptoms. Meta-analytic evidence has similarly suggested a reduction in pain after PRF, although heterogeneity across trials remains substantial [13-15,24,25]. Facial swelling was also lower with PRF, particularly on day 2. Several studies have reported reduced edema after PRF placement [9,10,15,22,23], but not all trials have reproduced this observation. Gülşen and Şentürk found no significant difference between PRF and control sides for edema or pain in their split-mouth study [16]. Such conflicting results may reflect differences in facial measurement methods, surgical complexity, corticosteroid use, cooling protocols, centrifugation settings, or the biological composition of the final platelet concentrate. Linear tape measurements are pragmatic but relatively insensitive to small changes and can introduce measurement error despite standardized landmarks. The greater postoperative mouth opening in the PRF group indicates less trismus. This finding is consistent with the concept that reduced local inflammation and pain can limit reflex muscular restriction after surgery. Nonetheless, the literature is mixed. Some randomized studies have demonstrated better interincisal opening with PRF [8,15,18], whereas systematic reviews have often found less consistent effects for trismus than for pain or alveolar osteitis [13,14,24,25]. The present difference of approximately 3 mm during the early postoperative phase is modest but could still be relevant to eating and oral hygiene. The most direct healing outcome in this study was the Landry index. Higher scores at days 3, 7, and 14 suggest that PRF accelerated early mucosal repair rather than simply reducing symptoms. Better soft-tissue healing after PRF has also been reported by Varghese et al., Jeyaraj and Chakranarayan, and Dar et al. [17,22,23]. Afat et al. observed improved early mucosal healing with leukocyte- and platelet-rich fibrin, with or without hyaluronic acid [20]. The day-7 difference in the present study is therefore aligned with a body of clinical evidence suggesting that the fibrin scaffold may be particularly useful during early socket epithelialization and granulation tissue maturation. The alveolar osteitis finding deserves attention because the complication is painful and resource-intensive. One of 50 PRF-treated patients and eight of 50 controls developed alveolar osteitis. Earlier randomized studies have also explored PRF as a preventive measure. Eshghpour and colleagues demonstrated a reduction in alveolar osteitis after mandibular third molar surgery, and Unsal and Erbasar found lower rates in PRF-treated sockets, particularly among smokers [19]. Systematic reviews by Canellas et al. and Al-Hamed et al. concluded that PRF may reduce alveolar osteitis, although study quality and outcome definitions varied [13,14]. The low event count in the present study means the risk ratio has a wide confidence interval and should not be read as a precise estimate of effect size. The exploratory radiographic result suggested greater socket fill at 3 months. Previous studies have produced inconsistent findings regarding hard-tissue regeneration. Gürbüzer et al. used scintigraphy to assess osteoblastic activity [6]. Kumar et al., Varghese et al., Jeyaraj and Chakranarayan, and Dar et al. reported varying degrees of radiographic benefit [8,17,22,23]. In contrast, the 2017 systematic review by Al-Hamed et al. did not find convincing evidence that PRF improved bone healing after mandibular third molar extraction [13]. This discrepancy highlights an important methodological issue: conventional radiographic density is not equivalent to histologic bone formation, and gray values are influenced by exposure parameters and image processing. The bone-fill outcome in this study should therefore be viewed as hypothesis-generating. The results also need to be interpreted in the context of PRF protocol variability. Centrifugation speed, rotor radius, tube material, delay before centrifugation, clot handling, and compression can alter cellular distribution and fibrin architecture. Clinical papers have used the umbrella term PRF for preparations that are biologically different. This problem was recognized in the classification of platelet concentrates and remains relevant when comparing contemporary L-PRF, A-PRF, and other derivatives [5,25]. The present protocol used a conventional leukocyte- and platelet-rich fibrin approach, and the results should not automatically be generalized to all platelet concentrate systems. Strengths of the study include randomized allocation, concealed treatment assignment until socket preparation, a standardized surgical protocol, assessor blinding for postoperative measurements, a clinically interpretable primary endpoint, and simultaneous evaluation of pain, edema, trismus, analgesic use, healing, and complications. The groups were also well balanced for impaction type and operative duration, reducing confounding by surgical difficulty. Several limitations remain. The study was conducted at one institution and involved relatively young, medically fit adults, so generalizability to older patients or those with systemic conditions is uncertain. The surgeon could not be blinded. Facial swelling was measured with linear distances rather than three-dimensional imaging. Platelet counts and growth-factor concentrations were not quantified, so biological variation between individual PRF preparations was not measured. The radiographic bone outcome was exploratory and did not use histology or standardized cone-beam computed tomography. Finally, the number of alveolar osteitis and infection events was small, and larger multicenter trials are needed for precise estimates of complication reduction. Overall, the pattern of findings supports PRF as a relatively simple autologous adjunct that may improve the early postoperative course after mandibular third molar surgery. The most defensible clinical interpretation is not that PRF eliminates postoperative morbidity, but that it can modestly improve early recovery and socket healing when prepared and applied in a standardized manner. This interpretation is consistent with recent pre-2024 evidence syntheses, which generally favor blood concentrates for early symptoms while emphasizing low certainty, protocol heterogeneity, and the need for better-designed randomized studies [24,25].

Placement of autologous platelet-rich fibrin in mandibular third molar extraction sockets was associated with better early soft-tissue healing, lower postoperative pain and analgesic use, less facial swelling, and faster recovery of mouth opening compared with conventional socket healing. Alveolar osteitis was also less frequent in the PRF group. A modest improvement in exploratory radiographic bone fill was observed at 3 months, but this finding requires confirmation with more rigorous hard-tissue assessment. PRF appears to be a useful adjunct for improving early postoperative recovery, provided that preparation and surgical protocols are standardized. Larger multicenter randomized trials should focus on clinically meaningful endpoints, standardized PRF characterization, and longer-term periodontal and osseous outcomes.

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