Journal of Multidisciplinary Dental Research
DOI: 10.38138/JMDR/v12i1.25.39
Volume: 12, Issue: 1, Pages: 34-39
Review Article
Shaik Amrulla1, Anupama Rao2*, K S Rajesh3
1Post graduate, Department of Periodontology, Yenepoya, Karnataka, India
2Additional Professor, Department of Periodontology, Yenepoya, Karnataka, India
3Professor, Department of Periodontology, Yenepoya, Karnataka, India
*Corresponding Author
Email: [email protected]
Received Date:28 August 2025, Accepted Date:23 January 2026, Published Date:09 July 2026
Platelet-rich fibrin (PRF) has evolved from a simple autologous clot into a versatile, bioactive scaffold that can be tailored through centrifugation physics, tube surface chemistry, and post-processing techniques. This narrative review synthesizes the last decade of evidence (2014–2025) on “next-generation” PRF variants—including advanced PRF (A-PRF+), injectable PRF (i-PRF), titanium-prepared PRF (T-PRF), lyophilized and compressed membranes, and emerging exosome-enriched hybrids—and evaluates their physicochemical attributes, biological performance, and clinical utility in periodontal regeneration. Compared with classic leukocyte-PRF, next-generation formulations display denser, more mature fibrin architectures, prolonged and higher-amplitude release of growth factors (PDGF-AB, VEGF, TGF-β1), and enriched leukocyte and progenitor-cell cargos that collectively enhance angiogenesis, osteogenesis, and immunomodulation. Human randomized controlled trials demonstrate that adjunctive use of A-PRF+ or i-PRF yields an additional 0.9–1.4 mm of clinical attachment gain and 20–35 % greater defect fill in intrabony lesions versus open-flap debridement alone, with reduced postoperative pain and morbidity. T-PRF membranes have shown superior tensile strength and volumetric stability for sinus-floor elevation and ridge-preservation procedures. Despite promising outcomes, heterogeneity in centrifugation parameters and a paucity of long-term histologic data limit meta-analytic certainty. Standardization of protocols, rigorous head-to-head trials, and integration with 3-D bioprinting and drug-delivery platforms are critical to unlocking the full translational potential of next-generation PRF. Collectively, these advances position PRF as a customizable, cost-effective, and chair-side biotherapeutic that bridges the gap between biological principles and predictable clinical regeneration in periodontology.
Keywords: Periodontal regeneration, Growth-factor release, Tissue engineering, Platelet-rich fibrin
1. Guo S, Dipietro LA. Factors Affecting Wound Healing. Journal of Dental Research. 2010; 89 (3). Available from: https://doi.org/10.1177/0022034509359125
2. Gosain A, DiPietro LA. Aging and Wound Healing. World Journal of Surgery. 2004; 28 (3). Available from: https://doi.org/10.1007/s00268-003-7397-6
3. Eming SA, Brachvogel B, Odorisio T, Koch M. Regulation of angiogenesis: Wound healing as a model. Progress in Histochemistry and Cytochemistry. 2007; 42 (3). Available from: https://doi.org/10.1016/j.proghi.2007.06.001
4. Nurden AT. Platelets, inflammation and tissue regeneration. Thrombosis and Haemostasis. 2011; 105 (S 06). Available from: https://doi.org/10.1160/ths10-11-0720
5. Agrawal AA. Evolution, current status and advances in application of platelet concentrate in periodontics and implantology. World Journal of Clinical Cases. 2017; 5 (5). Available from: https://doi.org/10.12998/wjcc.v5.i5.159
6. Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: A review and author′s perspective. Journal of Cutaneous and Aesthetic Surgery. 2014; 7 (4). Available from: https://doi.org/10.4103/0974-2077.150734
7. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends in Biotechnology. 2009; 27 (3). Available from: https://doi.org/10.1016/j.tibtech.2008.11.009
8. John PK, Valliaveettil TG, George AK, Pyas AM. Platelet concentrates for periodontal regeneration. Annals of Dentistry. 2020; 27 Available from: https://doi.org/10.22452/adum.vol27no9
9. Narang I, Mittal N, Mishra N. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: A clinical study. Contemporary Clinical Dentistry. 2015; 6 (1). Available from: https://doi.org/10.4103/0976-237x.149294
10. Li X, Cheng YH, Roman J, Mao HQ. Biomimetic Nanofibers as Artificial Stem Cell Niche. Biology and Engineering of Stem Cell Niches. 2017; Available from: https://doi.org/10.1016/b978-0-12-802734-9.00026-3
11. Araújo CRG, Araújo RC de, Araújo CG, Carvalho AP, Cota LOM, Martins-Júnior PA, et al. Bone Regeneration in the Anterior Maxilla With Titanium Mesh and Advanced-Platelet-Rich Fibrin: A Case Report With 2-Year Follow-up. Journal of Oral Implantology. 2024; 50 (5). Available from: https://doi.org/10.1563/aaid-joi-d-23-00154
12. Bahammam MA, Attia MS. Expression of Vascular Endothelial Growth Factor Using Platelet Rich Fibrin (PRF) and Nanohydroxyapatite (nano-HA) in Treatment of Periodontal Intra-Bony Defects - A Randomized Controlled Trial. Saudi Journal of Biological Sciences. 2021; 28 (1). Available from: https://doi.org/10.1016/j.sjbs.2020.11.027
13. Dos Santos Guimarães LH, Neto AR, De Oliveira TL, Da Silva Kataoka MS, Pinheiro JD, Júnior SD. Platelet-rich fibrin stimulates the proliferation and expression of proteins related to survival, adhesion, and angiogenesis in gingival fibroblasts cultured on a titanium nano-hydroxyapatite-treated surface. Journal of Oral Biosciences. 2024; 66 (1). Available from: https://doi.org/10.1016/j.job.2023.11.008
14. Zhao JH, Bai L, An SH. Effects of PRF on angiogenesis and collagen maturation: systematic review. Journal of Periodontology. 2019;90(12):1419–29.
15. Wang Z, Mudalal M, Sun Y, Liu Y, Wang J, Wang Y, et al. The Effects of Leukocyte-Platelet Rich Fibrin (L-PRF) on Suppression of the Expressions of the Pro-Inflammatory Cytokines, and Proliferation of Schwann Cell, and Neurotrophic Factors. Scientific Reports. 2020; 10 (1). Available from: https://doi.org/10.1038/s41598-020-59319-2
16. Mudalal M, Wang Z, Mustafa S, Liu Y, Wang Y, Yu J, et al. Effect of Leukocyte-Platelet Rich Fibrin (L-PRF) on Tissue Regeneration and Proliferation of Human Gingival Fibroblast Cells Cultured Using a Modified Method. Tissue Engineering and Regenerative Medicine. 2021; 18 (5). Available from: https://doi.org/10.1007/s13770-021-00360-1
17. Miron RJ, Moraschini V, Estrin NE, Shibli JA, Cosgarea R, Jepsen K, et al. Periodontal regeneration using platelet‐rich fibrin. Furcation defects: A systematic review with meta‐analysis. Periodontology 2000. 2025; 97 (1). Available from: https://doi.org/10.1111/prd.12583
18. Kotecha SV, Jaiswal P, Bhagat S. Comparative Evaluation of Autologous Sticky Bone, Platelet-Rich Fibrin, and Octacalcium Phosphate–Coated Deproteinized Bovine Bone Material for the Regeneration of Human Periodontal Infrabony Defects: Protocol for a Randomized Controlled Clinical Trial. JMIR Research Protocols. 2025; 14 Available from: https://doi.org/10.2196/69666
19. Harshavardhana B, Gupta N, Vantary SR, Krishna A. Clinical evaluation of platelet rich fibrin as barrier membrane in treatment of grade II furcation defects. Journal of Indian Society of Periodontology. 2024; 28 (4). Available from: https://doi.org/10.4103/jisp.jisp_6_24
20. Husak V, Povelychenko O, Maltseva V, Romanenko K, Vorontsov P, Pazdnikov R. Growth factor and cell content in Platelet-Rich Plasma (PRP), Leukocyte- and Platelet-Rich Plasma (L-PRP), Platelet-Rich Fibrin (PRF) in patients with long bone defects from combat injuries. BMC Musculoskeletal Disorders. 2025; 26 (1). Available from: https://doi.org/10.1186/s12891-025-09346-9
21. Bai M-Y, Wang C-W, Wang J-Y, Lin M-F, Chan WP. Three-dimensional structure and cytokine distribution of platelet-rich fibrin. Clinics. 2017; 72 (2). Available from: https://doi.org/10.6061/clinics/2017(02)09
22. Miron RJ, Moraschini V, Del Fabbro M, Piattelli A, Fujioka-Kobayashi M, Zhang Y, et al. Use of platelet-rich fibrin for the treatment of gingival recessions: a systematic review and meta-analysis. Clinical Oral Investigations. 2020; 24 (8). Available from: https://doi.org/10.1007/s00784-020-03400-7
23. Liu Y, Sun X, Yu J, Wang J, Zhai P, Chen S, et al. Platelet-Rich Fibrin as a Bone Graft Material in Oral and Maxillofacial Bone Regeneration: Classification and Summary for Better Application. BioMed Research International. 2019; 2019 Available from: https://doi.org/10.1155/2019/3295756
24. Miron RJ, Moraschini V, Fujioka-Kobayashi M, Zhang Y, Kawase T, Cosgarea R, et al. Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis. Clinical Oral Investigations. 2021; 25 (5). Available from: https://doi.org/10.1007/s00784-021-03825-8
25. Verma UP, Yadav RK, Dixit M, Gupta A. Platelet-rich fibrin: A paradigm in periodontal therapy – A systematic review. Journal of International Society of Preventive and Community Dentistry. 2017; 7 (5). Available from: https://doi.org/10.4103/jispcd.jispcd_429_16
26. Moraschini V, Barboza E dos SP. Use of Platelet‐Rich Fibrin Membrane in the Treatment of Gingival Recession: A Systematic Review and Meta‐Analysis. Journal of Periodontology. 2016; 87 (3). Available from: https://doi.org/10.1902/jop.2015.150420
27. Castro AB, Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, et al. Regenerative potential of leucocyte‐ and platelet‐rich fibrin. Part A: intra‐bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta‐analysis. Journal of Clinical Periodontology. 2017; 44 (1). Available from: https://doi.org/10.1111/jcpe.12643
28. Aleksić Z, Janković S, Dimitrijević B, Divnić-Resnik T, Milinković I, Leković V. The use of platelet-rich fibrin membrane in gingival recession treatment. Srpski arhiv za celokupno lekarstvo. 2010; 138 (1-2). Available from: https://doi.org/10.2298/sarh1002011a
29. Jankovic S, Aleksic Z, Klokkevold P, Lekovic V, Dimitrijevic B, Kenney EB, et al. Use of platelet-rich fibrin membrane following treatment of gingival recession: a randomized clinical trial. The International Journal of Periodontics and Restorative Dentistry. 2012;32(2):e41-50. https://pubmed.ncbi.nlm.nih.gov/22292152/
30. Keceli HG, Kamak G, Erdemir EO, Evginer MS, Dolgun A. The Adjunctive Effect of Platelet‐Rich Fibrin to Connective Tissue Graft in the Treatment of Buccal Recession Defects: Results of a Randomized, Parallel‐Group Controlled Trial. Journal of Periodontology. 2015; 86 (11). Available from: https://doi.org/10.1902/jop.2015.150015
31. Rajaramv T, Aarig K. Platelet Rich Fibrin in double lateral sliding bridge flap procedure for gingival recession coverage: An original study. Journal of Indian Society of Periodontology. 2015; 19 (6). Available from: https://doi.org/10.4103/0972-124x.164764
32. Jang E-S, Park J-W, Kweon H, Lee K-G, Kang S-W, Baek D-H, et al. Restoration of peri-implant defects in immediate implant installations by Choukroun platelet-rich fibrin and silk fibroin powder combination graft. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2010; 109 (6). Available from: https://doi.org/10.1016/j.tripleo.2009.10.038
33. Medikeri SR, Meharwade V, Wate MP, Lele VS. Effect of PRF and Allograft Use on Immediate Implants at Extraction Sockets with Periapical Infection —Clinical and Cone Beam CT Findings—. The Bulletin of Tokyo Dental College. 2018; 59 (2). Available from: https://doi.org/10.2209/tdcpublication.2017-0021
34. Choukroun J, Ghanaati S. Introducing the Low‐Speed Centrifugation Concept. Platelet Rich Fibrin in Regenerative Dentistry: Biological Background and Clinical Indications. 2017; Available from: https://doi.org/10.1002/9781119406792.ch3
35. Egle K, Salma I, Dubnika A. From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release. International Journal of Molecular Sciences. 2021; 22 (21). Available from: https://doi.org/10.3390/ijms222111553
36. Breme HJ, Biehl V, Helsen JA. Metals and implants. In: Helsen JA, Breme HJ, editors. Metals as Biomaterials. Chichester, UK: John Wiley & Sons; 1998. p. 37–72.
37. Park JB. Metallic biomaterials,” in The Biomedical Engineering Handbook. Bronzino JD, editor. Boca Raton, Fla, USA: CRC Press; 1940.
38. Tunalı M, Özdemir H, Küçükodacı Z, Akman S, Yaprak E, Toker H, et al. A Novel Platelet Concentrate: Titanium-Prepared Platelet-Rich Fibrin. BioMed Research International. 2014; 2014 Available from: https://doi.org/10.1155/2014/209548
39. Awad ZI, Beit ZZK. The use of platelet-rich fibrin prepared with titanium tubes (T-PRF) in external maxillary sinus lift combined with simultaneous implant placement (case series). International Journal of Surgery Case Reports. 2025; 136 Available from: https://doi.org/10.1016/j.ijscr.2025.111994
40. Gollapudi M, Bajaj P, Oza RR. Injectable Platelet-Rich Fibrin - A Revolution in Periodontal Regeneration. Cureus. 2022; 14 (8). Available from: https://doi.org/10.7759/cureus.28647
41. Farshidfar N, Amiri MA, Jafarpour D, Hamedani S, Niknezhad SV, Tayebi L. The feasibility of injectable PRF (I-PRF) for bone tissue engineering and its application in oral and maxillofacial reconstruction: From bench to chairside. Biomaterials Advances. 2022; 134 Available from: https://doi.org/10.1016/j.msec.2021.112557
42. Ngah NA, Dias GJ, Tong DC, Mohd Noor SNF, Ratnayake J, Cooper PR, et al. Lyophilised Platelet-Rich Fibrin: Physical and Biological Characterisation. Molecules. 2021; 26 (23). Available from: https://doi.org/10.3390/molecules26237131
43. Wei Y, Cheng Y, Wei H, Wang Y, Zhang X, Miron RJ, et al. Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin. Platelets. 2024; 35 (1). Available from: https://doi.org/10.1080/09537104.2024.2316745
44. Bakadia BM, Qaed Ahmed AA, Lamboni L, Shi Z, Mutu Mukole B, Zheng R, et al. Engineering homologous platelet-rich plasma, platelet-rich plasma-derived exosomes, and mesenchymal stem cell-derived exosomes-based dual-crosslinked hydrogels as bioactive diabetic wound dressings. Bioactive Materials. 2023; 28 Available from: https://doi.org/10.1016/j.bioactmat.2023.05.002
45. Gao W, Zhang Y, Zhang Q, Zhang L. Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery. Annals of Biomedical Engineering. 2016; 44 (6). Available from: https://doi.org/10.1007/s10439-016-1583-9
46. Yi K, Li Q, Lian X, Wang Y, Tang Z. Utilizing 3D bioprinted platelet-rich fibrin-based materials to promote the regeneration of oral soft tissue. Regenerative Biomaterials. 2022; 9 Available from: https://doi.org/10.1093/rb/rbac021
47. de Souza Araújo IJ, Perkins RS, Ibrahim MM, Huang GT-J, Zhang W. Bioprinting PDLSC-Laden Collagen Scaffolds for Periodontal Ligament Regeneration. ACS Applied Materials & Interfaces. 2024; 16 (44). Available from: https://doi.org/10.1021/acsami.4c13830
48. Niemczyk W, Żurek J, Niemczyk S, Kępa M, Zięba N, Misiołek M, et al. Antibiotic-Loaded Platelet-Rich Fibrin (AL-PRF) as a New Carrier for Antimicrobials: A Systematic Review of In Vitro Studies. International Journal of Molecular Sciences. 2025; 26 (5). Available from: https://doi.org/10.3390/ijms26052140
49. Rios HF, Lin Z, Oh B, Park CH, Giannobile WV. Cell‐ and Gene‐Based Therapeutic Strategies for Periodontal Regenerative Medicine. Journal of Periodontology. 2011; 82 (9). Available from: https://doi.org/10.1902/jop.2011.100710
50. Schneider M, Stamm C, Brockbank KGM, Stock UA, Seifert M. The choice of cryopreservation method affects immune compatibility of human cardiovascular matrices. Scientific Reports. 2017; 7 (1). Available from: https://doi.org/10.1038/s41598-017-17288-z
51. Bains VK, Mahendra J, Mittal M, Bedi M, Mahendra L. Technical considerations in obtaining platelet rich fibrin for clinical and periodontal research. Journal of Oral Biology and Craniofacial Research. 2023; 13 (6). Available from: https://doi.org/10.1016/j.jobcr.2023.09.003
© 2026 Published by International Dental Educationists’ Association (IDEA). This is an open-access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
Shaik Amrulla, Anupama Rao, K S Rajesh. Next-Generation Platelet-Rich Fibrin: Emerging Paradigms in Periodontal Regeneration and Healing. J Multi Dent Res. 2026;12(1):34-39. https://doi.org/10.38138/JMDR/v12i1.25.39
Subscribe now for latest articles, news.
