Effectiveness of Autologous Plasma Rich in Growth Factors on Healing of Extraction Socket—A Systematic Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Questions
2.2. Study Eligibility
2.3. Study Identification
2.4. Study Selection
2.5. Risk of Bias Assessment
2.6. Data Extraction and Data Synthesis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| PRGF | Plasma Rich in Growth Factors |
References
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| Study | Reason for Exclusion |
|---|---|
| Fok & Jin (2024) [31] | Review article—not original research/not RCT |
| Laforgia et al. (2024) [32] | Systematic review—secondary evidence |
| Al-Maawi et al. (2021) [33] | Systematic review—not primary RCT data |
| Ahmed et al. (2019) [34] | PRF used; not PRGF |
| Alzahrani et al. (2017) [35] | PRF used; not PRGF |
| Anitua et al. (2004) [36] | Narrative description; not clinical study |
| Anitua et al. (2007) [37] | Not extraction study; PRGF conceptual, not used for extraction socket healing |
| Anwandter et al. (2016) [38] | PRF (L-PRF) used; not PRGF |
| Asutay et al. (2017) [39] | PRF used, not PRGF |
| Borsani et al. (2018) [40] | In vitro study; not human clinical trial |
| Castro et al. (2021) [41] | PRF variants; not PRGF |
| Choukroun et al. (2006) [42] | PRF method; not PRGF |
| Clark et al. (2018) [43] | Mixed interventions; not PRGF-only |
| Dohan Ehrenfest et al. (2010) [44] | In vitro cell culture; not human clinical study |
| Dohan Ehrenfest et al. (2012) [45] | In vitro comparative analysis |
| Dutta et al. (2016) [46] | Comparison included PRP/PRF/HA; not PRGF-specific |
| Fang et al. (2022) [47] | PRGF not used; CGF fibrin |
| Girish Kumar et al. (2018) [48] | PRF used; not PRGF |
| Ghanaati et al. (2018) [49] | Review article |
| Giudice et al. (2019) [50] | Not PRGF; APRF & LPRF used |
| Guo et al. (2022) [51] | Animal study (rats) |
| Hauser et al. (2013) [52] | PRF used; not PRGF |
| Hatakeyama et al. (2014) [53] | Animal study (dogs) |
| Kamal et al. (2020) [54] | Condition not relevant (alveolar osteitis) |
| Kobayashi et al. (2016) [55] | In vitro growth factor release study |
| Kubesch et al. (2018) [56] | Animal study (in vivo experimental) |
| Mogharehabed et al. (2014) [57] | Animal study (dogs) |
| Mozzati et al. (2022) [58] | CGF used; not PRGF |
| Santos Pereira et al. (2023) [59] | Systematic review—secondary evidence |
| Schär et al. (2015) [60] | In vitro study |
| Semkin et al. (2022) [61] | Non-English publication (Russian) |
| Simon et al. (2009) [62] | Comparative study with bone grafts; not PRGF-only |
| Srinivas et al. (2018) [63] | PRF used; not PRGF |
| Starzyńska et al. (2021) [64] | Advanced platelet-rich fibrin (A-PRF), NOT PRGF |
| Tatullo et al. (2012) [65] | PRF used, not PRGF |
| Thakkar et al. (2016) [66] | DFDBA with PRF; not PRGF |
| Authors/Year | Study Type | Population | Intervention | Control | Follow-Up Period | Primary Outcomes | Secondary Outcomes | Conclusion |
|---|---|---|---|---|---|---|---|---|
| O’Sullivan L. et al./2022 [19]. | Prospective Double-blind Randomized Controlled Trial, parallel group design | 74 patients (36 PRGF,38 Control) aged 18–40 (28.1 ± 5.8) undergoing impacted mandibular third molar removal | Autologous PRGF application in surgical sockets | Standard surgical procedure without PRGF | 3 days and 7 days | Pain (NRS scale), Quality of Life (OHIP-14), Postoperative Symptom Severity (PoSSe) | Mouth opening (MIO), dry socket incidence, socket healing (Landry index), analgesic consumption | Pain scores slightly higher in PRGF group on day 3. No significant differences in OHIP-14 or PoSSe. Secondary outcomes showed no significant differences. |
| Brazdeikytė V. et al./2021 [24]. | prospective, single-center parallel multiple-group randomized Controlled Trial | 43 patients (33 female, 10 male) with mandibular molar extraction (mean age 28.6 y) (aged 18–48 years) | PRGF and PRF application for socket regeneration | Hemostatic sponge with gentamicin | 1 day and 7 days | Bone regeneration evaluated via CBCT, pain (VAS) | Vertical and diagonal bone loss in alveolus | PRGF had better osteoblastic properties and lower postoperative pain than PRF. Vertical dimensions were preserved in PRGF group but reduced in PRF group. |
| Stumbras A. et al./2020 [22]. | Randomized Controlled parallel-design Trial | 60 patients with alveolar ridge preservation | PRGF application vs. xenografts and allografts | Control group without socket preservation | 12 weeks | Bone regeneration, ridge width preservation | CBCT measurements | PRGF was equally effective as xenografts/allografts in ridge preservation and bone regeneration. |
| King E.M. et al./2018 [27]. | Single-center, single-blind parallel Randomized Controlled Trial | 38 patients (20 male and 18 female) mean age 40.7 ± 17.3, with alveolar osteitis (44 sockets) | PRGF applied in sockets | Alvogyl treatment | 3 days, 7 days | Pain, bone coverage, inflammation, halitosis | Quality of life, dysgeusia | PRGF showed faster bone coverage, reduced inflammation, and halitosis but no differences in pain or quality of life. |
| Anitua E. et al./2015 [28]. | Randomized, conventional-treatment, Controlled parallel-design Clinical Trial | 60 patients (Median 57 y for PRGF, 53.0 Y control) with mandibular molar extraction 36 subjects PRGF, 24 Control | Autologous PRGF application in extraction sockets | Conventional healing with blood clot | 3 days, 7 days, 15 days | Percentage of regenerated socket volume ≥ 75%, bone density | Pain, inflammation, soft tissue healing scores, histological outcomes | PRGF showed significant improvement in socket regeneration, reduced pain, and inflammation, with enhanced soft tissue healing and bone density. |
| Farina R. et al./2013 [12]. | Parallel-arm, open-label, Controlled Clinical Trial | 28 patients (mean age-55.2 y, 13 male 15 female). | PRGF application in sockets | Spontaneous healing | 4 to 6 weeks, 7 to 10 weeks | Bone volume, tissue mineral content, bone deposition | Histomorphometric markers (CD68+, OCN) | No significant enhancement in early bone deposition with PRGF compared to control. |
| Mozzati M. et al./2010 [18]. | Split-mouth Clinical Trial | 60 patients (18–35 y, 22.5 y mean) undergoing bilateral third molar extractions. | Autologous PRGF application in one socket; control with standard care | No PRGF application | 2 h and 7 days | Pain, swelling, and healing time | Cytokine production (TNF-α, IL-6) | PRGF reduced pain and swelling and accelerated healing. Cytokine levels were modulated in PRGF-treated sockets. |
| Authors | Mineralized Tissue (PRGF Group) | Mineralized Tissue (Control) | Non-Mineralized Tissue (PRGF Group) | Non-Mineralized Tissue (Control) | Healing Index (PRGF Group) | Healing Index (Control) | Pain (PRGF Group) | Pain (Control) | p-Value |
|---|---|---|---|---|---|---|---|---|---|
| O’Sullivan L. et al./2022 [19]. | NR | NR | NR | NR | Landry 3.6 ± 1.2 | Landry 4.0 ± 1.2 | NRS 2.7 ± 2.2 | NRS 3.2 ± 2.6 | p > 0.05 |
| Brazdeikytė V. et al./2021 [24]. | 8.2–10.3 mm | 7.5–10.0 mm | NR | NR | NR | NR | VAS 4.4 ± 2.6 * | VAS 5.1 ± 2.8 | p < 0.05 |
| Stumbras A. et al./2020 [22]. | 75.5 ± 16.3% * | 46.5 ± 15.2% | 24.4 ± 16.3% * | 53.5 ± 15.2% | NR | NR | NR | NR | p < 0.05 |
| King E.M. et al./2018 [27]. | NR | NR | Bone coverage faster (PRGF) | Slower coverage (Alvogyl) | Landry 6.7 ± 2.7 | Landry 5.6 ± 2.9 | VAS 2.0 ± 2.0 | VAS 2.4 ± 2.6 | p > 0.05 pain; Sig inflammation |
| Anitua E. et al./2015 [28]. | 450.0 ± 106.7 HU ** | 318.2 ± 113.0 HU | 415.4 ± 140.7 (units) ** | 274.8 ± 36.0 | 4.97 ± 0.2 ** | 3.96 ± 0.6 | VAS 0.0 | VAS 0.0 | p = 0.0001 |
| Farina R. et al./2013 [12]. | 485.8 ± 73.1 mg/cm3 | 538.4 ± 106.6 mg/cm3 | NR | NR | NR | NR | NR | NR | p > 0.05 |
| Mozzati M. et al./2010 [18]. | NR | NR | Col I: 12 ± 2.8; Col III: 7 ± 1.8 (units) | Col I: 4 ± 0.9; Col III: 1.9 ± 0.3 (units) | NR | NR | VAS 0.19 cm | VAS 0.49 cm | p < 0.05 |
| Study | Randomization Bias | Deviations from Interventions Bias | Missing Data Bias | Outcome Measurement Bias | Reported Results Bias | Overall Risk |
|---|---|---|---|---|---|---|
| L. O’Sullivan et al. [19]. | Low | Low | Low | Low | Low | Low |
| Brazdeikytė V. et al. [24] | Low | Moderate | Low | Moderate | Moderate | Moderate |
| Stumbras A. et al. [22]. | Low | Low | Low | Low | Low | Low |
| King E.M. et al. [27] | Low | Low | Moderate | Low | Low | Low |
| Anitua E. et al. [28] | Low | Low | Low | Low | Low | Low |
| Farina R. et al. [12] | Low | Low | Low | Low | Low | Low |
| Mozzati M. et al. [18] | Moderate | Low | Moderate | Low | Low | Moderate |
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Eid Al-Thobaiti, Y.; Al Thomali, Y.; Basha, S.; Noor Mohamed, R.; Alhazmi, A.O.; Alzahrani, T.E.; Khalil Fahmi, M.; Alqarni, A. Effectiveness of Autologous Plasma Rich in Growth Factors on Healing of Extraction Socket—A Systematic Review. J. Clin. Med. 2026, 15, 593. https://doi.org/10.3390/jcm15020593
Eid Al-Thobaiti Y, Al Thomali Y, Basha S, Noor Mohamed R, Alhazmi AO, Alzahrani TE, Khalil Fahmi M, Alqarni A. Effectiveness of Autologous Plasma Rich in Growth Factors on Healing of Extraction Socket—A Systematic Review. Journal of Clinical Medicine. 2026; 15(2):593. https://doi.org/10.3390/jcm15020593
Chicago/Turabian StyleEid Al-Thobaiti, Yasser, Yousef Al Thomali, Sakeenabi Basha, Roshan Noor Mohamed, Azzah O. Alhazmi, Thamer E. Alzahrani, Mohammed Khalil Fahmi, and Ali Alqarni. 2026. "Effectiveness of Autologous Plasma Rich in Growth Factors on Healing of Extraction Socket—A Systematic Review" Journal of Clinical Medicine 15, no. 2: 593. https://doi.org/10.3390/jcm15020593
APA StyleEid Al-Thobaiti, Y., Al Thomali, Y., Basha, S., Noor Mohamed, R., Alhazmi, A. O., Alzahrani, T. E., Khalil Fahmi, M., & Alqarni, A. (2026). Effectiveness of Autologous Plasma Rich in Growth Factors on Healing of Extraction Socket—A Systematic Review. Journal of Clinical Medicine, 15(2), 593. https://doi.org/10.3390/jcm15020593

