The Effect of Advanced Platelet-Rich Fibrin on the Healing of Post-Extraction Sockets in Patients with Diabetes: Preliminary Findings from a Randomized Controlled Clinical Trial

Abstract

Purpose

Diabetes Mellitus (DM) represents a significant public health challenge globally, with a particularly high prevalence in Saudi Arabia. The rising incidence of DM has increased concerns about effective management strategies, especially in contexts involving surgical interventions such as dental extractions. Diabetic individuals frequently experience complications during postoperative healing, characterized by impaired tissue repair and increased susceptibility to infections. This study aimed to evaluate the effect of A-PRF on early post-extraction soft-tissue healing in patients with type 2 diabetes mellitus.

Materials and Methods

A randomized, split-mouth clinical trial with participant and outcome-assessor blinding was conducted at King Abdulaziz University Dental Hospital. Eight patients with type 2 diabetes mellitus undergoing dental extractions contributed 31 extraction sockets/sites for site-level analysis. Sites were allocated to A-PRF treatment or control, and socket area was digitally measured at baseline, 1 week, and 3 weeks after extraction. Linear mixed-effects models were used to account for repeated measurements within sockets and clustering of sockets within patients. Fixed effects included treatment group, time, and group-by-time interaction. Marginal mean contrasts were used to estimate within-group changes from baseline and between-group differences, with false discovery rate adjustment applied where appropriate.

Results

At baseline, mean socket area was similar between Control/No PRF and A-PRF sites. By 3 weeks, socket area decreased by −17.10 mm² in Control/No PRF sites and −21.97 mm² in A-PRF sites, with both reductions remaining statistically significant after FDR adjustment. However, between-group differences were not statistically significant at 1 week (−3.82 mm²; 95% CI −12.55 to 4.92; p=0.392) or 3 weeks (−4.78 mm²; 95% CI −13.51 to 3.96; p=0.284). The group-by-time interaction was also non-significant (p=0.532), and the average treatment effect was −2.84 mm² (95% CI −10.30 to 4.62; p=0.456).

Conclusion

A-PRF-treated sockets showed numerically greater reductions in residual socket area compared with control sites; however, the between-group differences were not statistically significant. These findings suggest that A-PRF may have a favorable healing trend in diabetic patients, but the results should be interpreted as preliminary and require confirmation in larger, adequately powered randomized trials.

Introduction

Diabetes mellitus (DM) is a long-lasting metabolic disorder that affects various physiological pathways related to tissue healing and has a considerable impact on oral health. Diabetes prevalence has been on the rise globally, making it a significant public health problem. Complications related to DM and associated microvasculature damage, alterations in inflammation, immune deficiency, and metabolism can all have adverse effects on tissue healing.1–3 Substantial evidence indicates that individuals with diabetes have a higher prevalence of oral complications, including periodontal disease, tooth loss, and impaired or delayed wound healing within the oral cavity.2,3 A population-based cohort study has also indicated that patients with diabetes have an increased risk of tooth extraction caused by periodontal problems when compared to people without diabetes.4 These observations emphasize the importance of optimizing healing following dental surgical procedures in this population.

Tooth removal triggers a series of biological events, including coagulation, inflammation, granulation tissue formation, proliferation, and tissue remodeling.5–8 Although extraction sockets generally heal predictably, diabetes may interfere with several stages of this process. Clinical studies have reported delayed socket healing in patients with diabetes, particularly during the early postoperative period, although the available evidence is not entirely consistent.9–13 Gadicherla et al reported differences in extraction-socket healing among non-diabetic, prediabetic, and type 2 diabetic patients, whereas other prospective studies suggest that adequately controlled diabetes may not result in clinically significant impairment of extraction-socket healing.9–12 Thus, the relationship between diabetes and post-extraction healing appears to be influenced by glycemic status and other patient- and site-related factors.

Delayed wound healing in diabetic patients results from various biological factors. One such factor is impaired microcirculatory function due to chronic hyperglycemia.14,15 Diabetes might also lead to changes in the immune response, leading to chronic inflammation as well as compromised activity of neutrophils and macrophages.13,15,16 Disruption of growth factor/cytokine regulation, problems with collagen production, and poor angiogenesis may continue to affect granulation tissue formation and epithelialization as well.14–17 There is also experimental evidence of macrophage polarization anomalies within diabetes-related extraction sockets, indicating the significance of inflammation imbalance in oral wound repair delay.13 Collectively, these mechanisms provide biological grounds for further study of regenerative local therapies that could promote angiogenesis, cell migration, and extracellular matrix formation within diabetic extraction sockets.

PRF (Platelet-rich Fibrin) is one such technique that uses an autologous platelet concentrate to support regeneration in oral and maxillofacial surgery. Unlike PRP (platelet-rich plasma), PRF does not use any anticoagulants and is a three-dimensional fibrin clot composed of platelets and leukocytes.18,19 This fibrin structure becomes the biological framework that facilitates cell migration and tissue organization, while simultaneously releasing growth factors associated with wound healing.18,20,21 Key mediators released from PRF include platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF), which support angiogenesis, chemotaxis, cellular proliferation, and extracellular-matrix remodeling.20,21

Researchers subsequently developed advanced platelet-rich fibrin (A-PRF) using a low-speed centrifugation concept intended to modify the cellular composition and biological characteristics of the fibrin matrix.22,23 Compared with conventional PRF protocols, low-speed centrifugation may retain more platelets and leukocytes within the fibrin matrix and may increase the release of selected growth factors.22,23 The resulting combination of a structural fibrin scaffold and sustained release of bioactive mediators provides a plausible biological basis for using A-PRF to support healing at extraction sites. This rationale may be particularly relevant in patients with diabetes, in whom impaired angiogenesis, altered inflammatory responses, and reduced tissue repair capacity may limit the normal healing response.

Clinical evidence on PRF in extraction-socket healing has generally come from populations not specifically selected for diabetes, and the findings have not been completely consistent. A systematic review by Al-Maawi et al evaluated 20 randomized controlled studies and reported that PRF was associated with improved early soft-tissue healing in most evaluated studies, as well as greater socket fill in many studies. However, the authors emphasized substantial heterogeneity in study protocols and outcome measures and could not perform a quantitative meta-analysis.24 Similarly, a systematic review and meta-analysis of autologous platelet concentrates reported potential benefits for post-extraction healing, although differences among platelet-concentrate preparations and clinical outcomes limit direct comparison between studies.25 These findings support the potential role of platelet concentrates in extraction-socket healing but also indicate that their clinical effects should be interpreted in relation to the specific preparation protocol and patient population.

Evidence specifically evaluating A-PRF in extraction sockets has also been mixed. Gupta and Agarwal evaluated A-PRF in a prospective split-mouth study involving patients undergoing bilateral impacted mandibular third-molar extraction and reported favorable healing outcomes in A-PRF-treated sockets compared with controls.26 However, other randomized clinical evidence has not consistently demonstrated an additional clinical benefit from advanced PRF preparations. Pereira et al evaluated A-PRF+ in a split-mouth randomized clinical trial of upper third-molar extraction sockets and reported no additional effect on socket healing compared with control sites.27 More recent randomized evidence has likewise highlighted variability in the effects of PRF-based interventions on early socket healing.28 These findings indicate that although A-PRF has a strong biological rationale and has shown promising results in some clinical settings, its clinical effectiveness cannot be assumed across different populations, extraction sites, preparation protocols, and outcome measures.

Importantly, evidence specifically involving patients with diabetes remains limited. A randomized split-mouth clinical trial involving 97 type 2 and 3 type 1 diabetic patients evaluated conventional PRF in extraction sockets and reported improvements in soft- and hard-tissue healing compared with untreated control sockets.29 This study provides clinically relevant evidence that platelet concentrates may benefit the healing of extraction sockets in diabetic patients. However, the intervention was conventional PRF rather than A-PRF, so it does not establish whether the modified low-speed centrifugation protocol and fibrin architecture of A-PRF provide additional clinical benefit in diabetic extraction sockets. Consequently, an important clinical gap remains regarding the effectiveness of A-PRF specifically for early extraction-socket healing in patients with type 2 diabetes.

The present study was designed to address this gap by evaluating A-PRF in a randomized split-mouth clinical trial of adults with type 2 diabetes undergoing bilateral tooth extraction. The study sought to determine whether application of A-PRF to one extraction socket, compared with conventional management of the contralateral socket, results in greater improvement in early soft-tissue healing. The primary outcome was the change in extraction-socket area from immediately after extraction to 1 and 3 weeks postoperatively, measured using standardized digital intraoral scanning. We hypothesized that A-PRF-treated sockets would demonstrate a greater reduction in socket area over the 3-week healing period than control sockets.

Material and Methods

Study Preparation

This randomized, controlled, patient- and outcome-assessor-blinded clinical trial was conducted at King Abdulaziz University Dental Hospital to assess the effect of advanced platelet-rich fibrin (A-PRF) on healing in post-extraction sockets in patients with diabetes. An external statistician reviewed the statistical design to ensure a robust research design and statistical accuracy. The King Abdulaziz University Faculty of Dentistry Research and Ethics Committee granted ethical approval (Approval #264-12-23). The clinical trial followed the Declaration of Helsinki (2013). The study was registered at Clinicaltrials.gov (registration ID: NCT07287475). Written informed consent from all participants was obtained after a clear and thorough explanation of the research aims and procedures. The trial period was from January 2026 to April 2026.

Sample and Study Design

An a priori sample-size calculation was performed using G*Power, with a two-sided alpha level of 0.05, 80% statistical power, and an assumed standardized effect size of 0.50, yielding a target sample size of 30 extraction sites. Eight patients with type 2 diabetes requiring bilateral extraction of the same type of tooth were recruited. Several participants contributed more than two extraction sites, resulting in 31 extraction sockets/sites available for site-level analysis. Each socket was assessed longitudinally at baseline, 1 week, and 3 weeks after extraction; therefore, the dataset included patient-level, socket-level, and repeated-measure observations.

Eligible patients were aged 18 years or older, had confirmed type 2 diabetes mellitus, either controlled or uncontrolled, and required bilateral dental extractions. Patients younger than 18 years, those with systemic diseases other than diabetes, bleeding disorders, pregnancy or lactation, or current tobacco use, including conventional or electronic tobacco products, were excluded. All patients underwent HbA1c testing before the procedure to assess glycemic control status. Patients were not selected based on extreme clinical conditions, and no differential selection strategy was used, in order to minimize selection bias.

A split-mouth, site-level design was used. Within each patient, extraction sockets were allocated to treatment or control conditions. One extraction site was randomly assigned to receive A-PRF, while the corresponding contralateral or comparable site served as the control. Randomization was performed using a computerized random number generator and was concealed until treatment assignment. The clinician performing the procedure was aware of the assigned treatment because of the nature of the intervention; however, patients and outcome assessors responsible for socket-area measurements were blinded throughout the study.

Because multiple sockets could be contributed by the same patient and each socket was measured repeatedly over time, observations were not statistically independent. Therefore, socket area outcomes were analyzed using linear mixed-effects models to account for the hierarchical and longitudinal structure of the data, with patient-level clustering, socket/site-level measurements, and repeated observations over time.

Clinical Procedure

All the procedures were carried out under local anesthesia by a single calibrated operator with a standardized, non-traumatic extraction technique to reduce variability.

A nurse collected venous blood into 9-mL tubes without anticoagulant, which were immediately centrifuged using a DM0412 clinical centrifuge equipped with the supplied CCEN-A01-001 rotor (DLAB Scientific Co., Ltd., Beijing, China) at 1300 rpm for 8 minutes. According to the manufacturer-reported rotor radius of 11 cm for 8.5–10 mL tubes, this setting corresponded to an RCF-max of approximately 208 × g. Following centrifugation, the A-PRF clot was carefully retrieved and separated from the red blood cell fraction. The clot was then placed in the plug-forming component of the Choukroun PRF Box (Process for PRF, Nice, France) and gently compressed to form an A-PRF plug suitable for placement within the extraction socket. The resulting A-PRF plug was adapted to the socket and placed directly into the test extraction site. The clinician sutured the A-PRF and control sockets with the same suture material, Vicryl 3–0, to maintain procedural uniformity. After suturing, patients were directed to the scanning station, where calibrated devices and a uniform scanning protocol were used to record digital intraoral scans.

Digital assessment of socket healing was performed using a Medit i700 Wireless intraoral scanner (Medit Corp., Seoul, Republic of Korea). Intraoral scans of the extraction sites and adjacent anatomical structures were obtained immediately after extraction (baseline) and at 1 and 3 weeks postoperatively using a standardized scanning approach. The resulting three-dimensional digital models were imported into Medit Design software (Medit Corp., Seoul, Republic of Korea). The margins of each extraction socket were identified and delineated, and the socket area was measured digitally at each time point. Changes in socket area from baseline to the subsequent follow-up visits were used to quantify the progression of soft-tissue healing. To assess intra-examiner reproducibility, socket-area measurements were repeated for 5 randomly selected scans after a two-week interval. Intra-examiner reliability was excellent (ICC = 0.94).

Outcome Measures

The primary outcome was the change in extraction-socket area from baseline to 1 and 3 weeks postoperatively, quantified using serial digital intraoral scans. Socket-area measurements were performed by a blinded outcome assessor.

Independent measures included the use of A-PRF, and dependent measures included scan-based healing parameters.

Environmental and Procedural Controls

The surgical setting, including lighting, sterilization procedures, and operator controls, was kept consistent across all cases to minimize experimental bias. Surgical tools, suture materials, scan devices, and procedure controls were the same for all patients. The same operatory and the same team of clinicians operated on all the patients.

Statistical Analysis

Descriptive statistics: Means (± SD) of socket area (mm²) were summarized for diabetic patients at baseline or immediately post-extraction (T1), 1 week (T2), and 3 weeks (T3) within each treatment group (Control vs A-PRF) in this split-mouth study.

Inferential analysis: Longitudinal and between-group differences were evaluated using linear mixed-effects models with fixed effects for group (Control vs A-PRF), time (T1, T2, T3), and their interaction (group×time); random effects were specified as sites (sockets) nested within subjects to account for within-site repeated measures. Pairwise comparisons (inter-group differences at each time point and intra-group change over time from baseline) were estimated from marginal means with false discovery rate (FDR) adjustment. A p-value of < 0.05 was considered statistically significant. Statistical analyses were performed using Stata version 17 (StataCorp LLC, College Station, TX).

Results

At baseline (T1), mean socket area was virtually identical between groups (Control: 25.67 ± 18.37 mm²; A-PRF: 25.43 ± 17.43 mm²). Both groups showed progressive reductions over time. By one week (T2), mean area declined to 16.33 ± 11.43 mm² in Control and 12.19 ± 8.51 mm² with A-PRF. By three weeks (T3), areas further decreased to 8.57 ± 7.80 mm² (Control) and 3.46 ± 3.16 mm² (A-PRF) (Table 1).

Table 1.

Descriptive Statistics of Socket Area (Mm²) Between Comparison Groups Across Different Time Points (N=31)

Socket Area (mm2)		Immediately Following Extraction (T1)	One Week After Extraction (T2)	Three Weeks After Extraction (T3)
Control/ No PRF (n=15)	Mean	25.67	16.33	8.57
	SD	18.37	11.43	7.80
A-PRF (n=16)	Mean	25.43	12.19	3.46
	SD	17.43	8.51	3.16

Notes: The study included 8 patients and 31 extraction sockets/sites. Each socket was measured at baseline (T1), 1 week (T2), and 3 weeks after extraction (T3). Descriptive statistics are reported at the socket/site level, while inferential comparisons were performed using mixed-effects models accounting for repeated measurements within sockets and clustering within patients.

Abbreviation: SD, Standard deviation.

Table 2 describes the intra-group change from baseline; Both groups showed significant reductions in socket area over time. In the Control/No-PRF group, T2–T1 was −9.34 mm² (95% CI −14.99 to −3.68; p=0.001, FDR-adjusted) and T3–T1 was −17.10 mm² (95% CI −22.75 to −11.45; p<0.001, FDR-adjusted). In the PRF group, T2–T1 was −13.24 mm² (95% CI −18.71 to −7.76; p<0.001, FDR-adjusted) and T3–T1 was −21.97 mm² (95% CI −27.44 to −16.49; p<0.001, FDR-adjusted).

Table 2.

Intra Group Comparisons with Baseline (N=31)

	Estimated Socket Area Difference from Baseline (mm2)		z	95% CI	p-Value
Control/ No PRF (n=15)	Time: T2 vs T1	−9.34	−3.24	[−14.99, −3.68]	0.001*
	Time: T3 vs T1	−17.10	−5.93	[−22.76, −11.44]	<0.001*
A-PRF (n=16)	Time: T2 vs T1	−13.24	−4.74	[−18.71, −7.76]	<0.001*
	Time: T3 vs T1	−21.97	−7.86	[−27.44, −16.49]	<0.001*

Notes: * Estimates and p-values from linear mixed-effects model (REML) with FDR adjustment. P-values < 0.05 considered significant. Negative values indicate decreases from baseline (healing).

Table 3 explains the inter-group comparisons (A-PRF treated − Control). At T1, the groups did not differ (mean difference 0.08 mm², 95% CI [−8.65, 8.82]; p=0.985, FDR-adjusted). At T2, A-PRF was lower by −3.82 mm² (95% CI [−12.55, 4.92]; p=0.392, FDR-adjusted), and at T3 by −4.78 mm² (95% CI [−13.51, 3.96]; p=0.284, FDR-adjusted); neither difference reached statistical significance. The group×time interaction was not significant (χ²(3)=2.20, p=0.532), indicating no evidence that the treatment effect varied over time; accordingly, the time-averaged treatment effect which was −2.84 mm² (95% CI [−10.30, 4.62]; p=0.456) was reported.

Table 3.

Inter Group Comparisons (A-PRF Treated – Control) at Each Time Point (N=31)

Time point	Mean Difference (A-PRF treated – control)	95% CI	p-Value
T1	0.08	[−8.65, 8.82]	0.985
T2	−3.82	[−12.55, 4.92]	0.392
T3	−4.78	[−13.51, 3.96]	0.284
Average Treatment Effect (A-PRF Treated − Control across time points)	−2.84	[−10.30, 4.62]	0.456‡

Notes: Estimates and p-values from linear mixed-effects model (REML) with FDR adjustment. P-values < 0.05 considered significant. Negative values indicate decreases from baseline (healing). ‡ Since the group×time interaction was non-significant [Joint test (df=3, χ²=2.20, p=0.532)], the average treatment effect was reported.

Figure 1 illustrates the longitudinal reduction in socket area in both groups from baseline (T1) to T3, with A-PRF-treated sites showing numerically smaller residual socket areas at follow-up; however, between-group differences were not statistically significant.

Figure 1.

Changes Over Time in Socket Area by Treatment Group.

Notes: Values represent mean ± SD socket area (mm²). Dashed lines show model-based longitudinal trends from baseline. * indicates significant within-group reduction from baseline after FDR adjustment (p < 0.05). No significant between-group differences were observed at any time point.

Discussion

The present randomized split-mouth clinical trial evaluated the effect of advanced platelet-rich fibrin (A-PRF) on early post-extraction socket healing in patients with type 2 diabetes mellitus. Both A-PRF-treated and control sockets demonstrated a progressive and statistically significant reduction in socket area during the three-week observation period. Although A-PRF-treated sites showed numerically smaller residual socket areas at both follow-up visits, the differences between the groups did not reach statistical significance. At 1 week, the estimated difference between A-PRF and control sites was −3.82 mm², while at 3 weeks it was −4.78 mm²; however, the corresponding confidence intervals included zero. Moreover, the group-by-time interaction was not significant, indicating insufficient evidence that the pattern of socket closure over time differed between A-PRF-treated and untreated sites. Thus, the present findings indicate a favorable numerical trend associated with A-PRF but do not demonstrate its superiority over spontaneous healing.

Despite the absence of a statistically significant treatment effect, the direction of the observed differences is biologically plausible. PRF provides a three-dimensional fibrin matrix containing platelets, leukocytes, and bioactive mediators involved in different stages of tissue repair. The fibrin network can serve as a provisional extracellular matrix that supports cellular migration and tissue organization, while platelet- and leukocyte-derived mediators contribute to angiogenesis, cell proliferation, extracellular-matrix synthesis, and remodeling. A-PRF was developed using the low-speed centrifugation concept, in which adjusting centrifugal force alters cellular distribution within the fibrin matrix and may increase the availability and release of growth factors such as platelet-derived growth factor, transforming growth factor-β, and vascular endothelial growth factor.22,23 These properties provide a reasonable biological basis for investigating A-PRF as an adjunct to extraction-socket healing, particularly in patients with compromised tissue repair.

This rationale may be especially relevant in diabetes, where several components of normal wound healing may be altered. Chronic hyperglycemia has been associated with microvascular dysfunction, dysregulated inflammatory responses, altered macrophage activity, impaired angiogenesis, and disturbances in collagen synthesis and extracellular matrix remodeling.13–16 These alterations can interfere with granulation tissue formation, epithelialization, and subsequent tissue maturation. The local delivery of a fibrin scaffold containing platelets, leukocytes, and their associated signaling molecules could therefore theoretically support some of the biological processes affected by diabetes. Nevertheless, the biological plausibility of such an effect should be distinguished from evidence of clinical efficacy. In the present study, the numerical advantage observed with A-PRF was not sufficiently large or precise to establish a statistically significant treatment effect.

Evidence specifically addressing PRF for extraction-socket healing in patients with diabetes remains limited. Of particular relevance, Asoka et al evaluated the effect of conventional PRF on post-extraction socket healing in a randomized split-mouth study involving 100 patients with diabetes, of whom 97 had type 2 diabetes and three had type 1 diabetes. PRF-treated sockets demonstrated significantly better soft- and hard-tissue healing than control sockets, whereas postoperative pain was comparable between the two sides. However, the study evaluated conventional PRF rather than A-PRF and used clinical and radiographic healing parameters, limiting direct comparison with the digital socket-area measurements used in the present study. Studies evaluating A-PRF specifically in extraction sockets have likewise produced inconsistent results. In a randomized split-mouth clinical trial, Gupta and Agarwal evaluated A-PRF following bilateral impacted mandibular third-molar extraction in 20 systemically healthy patients. A-PRF-treated sites demonstrated significantly better early soft-tissue healing and lower postoperative pain at selected time points, as well as improved radiographic bone-healing measures during follow-up. These findings support a potential benefit of A-PRF on extraction-socket healing; however, direct comparison with the present study is limited by important differences in study populations and outcome measures. Gupta and Agarwal included young, systemically healthy individuals undergoing impacted third-molar surgery, whereas the present study specifically evaluated patients with type 2 diabetes and quantified early socket closure using serial digital intraoral scanning.26 In contrast, Pereira et al investigated A-PRF+ in a split-mouth randomized clinical trial of maxillary third-molar extraction sockets and found no additional benefit in socket healing compared with untreated control sites.27 The latter finding is more consistent with the present study, in which A-PRF-treated sites showed numerically greater socket closure but no statistically significant treatment effect. Taken together, these findings suggest that the clinical effects of A-PRF may vary according to the surgical procedure, anatomical site, PRF preparation protocol, healing interval, and method used to evaluate healing.

Recent evidence further emphasizes this variability. Katz et al evaluated A-PRF+ following tooth extraction in a randomized clinical trial and assessed gingival micro perfusion, clinical wound healing, and postoperative pain. No significant differences between A-PRF+ and control groups were detected for gingival perfusion, wound healing, or pain during the first 10 postoperative days.28 These findings are particularly relevant because they demonstrate that the proposed biological effects of advanced PRF preparations do not necessarily translate into measurable improvements across all early clinical healing outcomes. The authors also suggested that the effect of PRF might be more apparent in more invasive procedures or compromised healing situations. The present diabetic population represents such a potentially compromised healing environment; nevertheless, even in this setting, the observed numerical advantage did not reach statistical significance.

The broader literature on PRF and extraction-socket healing is similarly heterogeneous. Al-Maawi et al systematically reviewed 20 randomized and/or controlled clinical studies evaluating PRF in extraction sockets and reported significantly improved soft-tissue healing at approximately one week in 75% of the studies that assessed this outcome. The review also suggested favorable effects of PRF on early postoperative pain and socket bone fill; however, substantial heterogeneity in study protocols and outcome assessment precluded meta-analysis. Consequently, while the cumulative evidence suggests that PRF may influence early socket healing, the magnitude and clinical relevance of this effect remain uncertain and cannot necessarily be extrapolated from one PRF formulation or patient population to another.

An important feature of the present investigation was the quantitative assessment of socket closure using serial digital intraoral scanning. Mean socket areas were nearly identical between groups immediately after extraction (25.43 mm² for A-PRF and 25.67 mm² for control sites), supporting baseline comparability. At 1 week, mean residual socket area had decreased to 12.19 mm² in the A-PRF group compared with 16.33 mm² in the control group, and by 3 weeks the corresponding values were 3.46 and 8.57 mm², respectively. These descriptive findings indicate a consistently smaller residual wound area in A-PRF-treated sockets during follow-up. Nevertheless, the between-group confidence intervals were relatively wide, and neither comparison reached statistical significance. The magnitude of the descriptive difference is therefore potentially clinically interesting, but it should be considered a signal for further investigation rather than evidence that A-PRF accelerates socket closure.

An additional methodological strength of the present study was the use of serial digital intraoral scanning to quantify changes in extraction-socket area. Digital scanning provides a non-invasive, patient-preferred approach for generating reproducible three-dimensional records of the extraction site and surrounding soft tissues, allowing longitudinal changes to be assessed without repeated conventional impressions or additional ionizing radiation. Previous clinical investigations have successfully used serial intraoral scans and superimposition of three-dimensional datasets to quantify post-extraction changes in soft-tissue contour, ridge dimensions, and wound closure.30–32 In the present study, digital scans were obtained immediately after extraction and at 1 and 3 weeks, and the socket margins were delineated to calculate residual socket area at each time point. This approach provided a continuous quantitative measure of early soft-tissue closure rather than relying exclusively on ordinal clinical healing indices. Nevertheless, reduction in the visible socket area represents only one component of the healing process and should not be considered a surrogate for underlying bone formation or preservation of alveolar ridge dimensions. Future studies combining serial intraoral scanning with radiographic or volumetric assessment may provide a more comprehensive evaluation of both soft- and hard-tissue healing. Another strength of the present study was its split-mouth design. By allocating treatment and control sites within the same individual, the design reduces the influence of inter-individual differences that could affect wound healing, including age, systemic disease characteristics, medication use, metabolic status, and individual inflammatory responses. This is particularly advantageous in diabetes, where considerable variability in disease duration and glycemic control may influence healing. In addition, the statistical analysis accounted for the hierarchical nature of the data by using mixed-effects models to address repeated observations within sockets and clustering of multiple sockets within individual participants. These methodological features strengthen the internal comparison between A-PRF-treated and control sites.

Limitations

Several limitations should be considered when interpreting the findings of the present study. First, although 31 extraction sockets were included in the analysis, these sites were derived from only eight patients. Including multiple sockets from individual participants increased the number of site-level observations but did not provide the same degree of independent information as recruiting more patients. Although the mixed-effects model accounted for socket clustering within participants and repeated measurements over time, the small patient-level sample reduced the precision of the estimated treatment effect and limited statistical power to detect potentially meaningful between-group differences. Accordingly, the absence of statistical significance should not be interpreted as evidence of equivalence between A-PRF and control treatment.

Second, the limited sample size precluded meaningful subgroup analyses according to glycemic control. HbA1c was recorded before treatment; however, the study was not sufficiently powered to determine whether response to A-PRF differed by degree of metabolic control. Because glycemic status may influence wound healing, future studies should include larger populations and prospectively evaluate HbA1c and other diabetes-related variables as potential modifiers of treatment response.

Third, although the split-mouth design reduced inter-individual variability by allowing comparison of treatment and control sites within the same patient, it could not completely eliminate site-specific differences. Variations in tooth type, socket morphology, extraction complexity, local tissue characteristics, and anatomical conditions may have influenced the healing response despite standardization of the surgical procedure.

Fourth, the follow-up period was limited to three weeks and therefore restricted to assessing early soft-tissue healing. Reduction in residual socket area should not be interpreted as evidence of enhanced bone formation or preservation of alveolar ridge dimensions. Longer follow-up incorporating radiographic or three-dimensional assessment would be required to determine whether A-PRF influences subsequent hard-tissue healing and alveolar remodeling.

Fifth, socket healing was primarily quantified by changes in the surface area of the extraction site using serial intraoral scans. Although this provided a quantitative, reproducible measure of wound closure, surface-area reduction represents only one dimension of the healing process and does not provide information on underlying bone formation or alveolar remodeling. In addition, patient-reported outcome measures (PROMs), including postoperative pain, swelling, discomfort, and satisfaction, were not available for analysis. Therefore, the study could not determine whether the observed changes in socket closure were accompanied by differences in patient-perceived recovery. Future studies should combine digital surface measurements with validated clinical healing indices, PROMs, and radiographic or three-dimensional assessments to provide a more comprehensive evaluation of post-extraction healing.

Finally, because this study was conducted at a single academic center, the findings may have limited generalizability. Larger multicenter randomized controlled trials including more diverse patients with type 2 diabetes are needed to confirm these observations and identify subgroups that may benefit most from A-PRF.

Impact of the Study

This study provides preliminary clinical evidence regarding the use of advanced platelet-rich fibrin (A-PRF) for post-extraction socket healing in patients with type 2 diabetes mellitus, a population in whom wound repair may be compromised. Although A-PRF-treated sockets demonstrated numerically greater reductions in residual socket area during the three-week healing period, the differences compared with control sites were not statistically significant. Therefore, the findings do not establish the clinical superiority of A-PRF but identify a potentially favorable healing trend that warrants further investigation.

The study also demonstrates the feasibility of using serial digital intraoral scanning as a non-invasive approach for quantitatively monitoring early soft-tissue socket closure. Combined with the split-mouth design, this methodology enabled longitudinal assessment of healing while minimizing inter-individual variability.

Given the limited clinical evidence specifically evaluating A-PRF in patients with diabetes, these preliminary findings contribute to the existing literature and provide a basis for larger, adequately powered randomized controlled trials. Future studies should incorporate longer follow-up, glycemic-control stratification, and combined soft- and hard-tissue outcomes to determine whether A-PRF provides a clinically meaningful benefit in this patient population.

Conclusion

Within the limitations of this randomized split-mouth clinical trial, both Control/No PRF and A-PRF-treated extraction sockets demonstrated progressive reductions in socket area over time, consistent with expected post-extraction healing. Although A-PRF-treated sites showed a favorable numerical trend toward smaller residual socket areas, the study did not demonstrate a statistically significant treatment effect over control.

These findings should therefore be interpreted as preliminary and hypothesis-generating rather than confirmatory evidence of clinical efficacy. The results do not yet support definitive conclusions regarding routine clinical use of A-PRF for post-extraction socket healing in patients with diabetes. Larger randomized controlled trials with longer follow-up periods are needed to determine whether A-PRF provides clinically meaningful benefits in this patient population.

Funding Statement

There is no funding to report.

Data Sharing Statement

The data supporting the findings of this study are not publicly available due to ethical and privacy restrictions related to participants’ confidentiality. However, anonymized data may be made available from the corresponding author upon reasonable request and with approval from the relevant institutional ethics committee.

Ethical Approval and Informed Consent

Ethical approval was granted by the King Abdulaziz University, Faculty of Dentistry, Research and Ethics Committee (Approval #264-12-23). The clinical trial followed the principles of the Declaration of Helsinki (2013). The study was registered at Clinicaltrials.gov (registration ID: NCT07287475). Written informed consent from all participants was obtained after a clear and thorough explanation of the research aims and procedures.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.