Periodontal regeneration and platelet concentrates: between biological promises and clinical realities

The management of chronic periodontitis aims at the restoration of the attachment apparatus (cementum, alveolar bone, and periodontal ligament), a major clinical challenge where conventional healing often results in a long junctional epithelium rather than regeneration ad integrum. While autologous platelet concentrates are widely used for their ability to release growth factors (PDGF, TGF-β, VEGF) and to stabilize the clot via a fibrin matrix, their effectiveness remains highly variable depending on the protocols used.

This literature review (including data up to March 2026) aims to synthesize biological mechanisms, clarify the classification of concentrates (from first-generation PRP to recent A-PRF, i-PRF, and T-PRF), and evaluate the strength of clinical evidence by indication. The study specifically seeks to identify current consensus, particularly for infra-bony defects, while highlighting areas of uncertainty related to the variability of centrifugation parameters.

The authors hypothesize that the clinical superiority of new PRF generations (A-PRF, T-PRF) remains to be demonstrated by high-powered randomized trials, despite theoretically optimized biological properties. The challenge is to determine whether these devices constitute a real systematic adjuvant or if their success depends primarily on extrinsic factors such as defect morphology or flap stability.

Methodology of the literature review

This publication constitutes a narrative review of the literature and not a systematic review; it therefore does not include a PRISMA diagram or a global quantitative analysis (meta-analysis). The authors conducted an electronic search on the PubMed/MEDLINE, Cochrane Library, Scopus, and Google Scholar databases, covering the period from their inception until March 2026.

The search strategy used combinations of keywords targeting platelet concentrates (PRP, PRF, A-PRF, i-PRF, T-PRF) and types of periodontal defects (infrabony, furcations, gingival recessions). Selection criteria included:

• Human clinical studies in English.
• Randomized controlled trials (RCTs).
• Pre-existing systematic reviews and meta-analyses.
• Biologically relevant experimental studies.

The selection process was carried out independently by two authors, with disagreements resolved by consensus. Exclusions included conference abstracts, editorials, and letters. The strength of evidence ("strong", "moderate", or "emergent") was assigned via a qualitative assessment based on the number, consistency, and methodological design of the studies identified for each clinical indication.

Biological bases and kinetics of growth factors

The biological efficacy of platelet concentrates is based on the release of bioactive mediators from alpha granules. This review identifies five key growth factors whose roles are specific to periodontology regeneration:

The fibrin matrix acts as a three-dimensional scaffold. Unlike an immediate massive release, this structure allows for a gradual diffusion of mediators, essential for coordinating the periodontal healing sequence and stabilizing the clot against the mechanical stresses of the flap.

Classification and specifics of preparations

Concentrates are segmented according to their preparation method and fibrin architecture:

• Platelet-Rich Plasma (PRP): First generation requiring anticoagulants and exogenous activation (calcium chloride or thrombin). Its use in gel or liquid form is documented, although platelet yields are variable.
• Platelet-Rich Fibrin (PRF): Obtained by simple centrifugation without anticoagulant. It is the most documented preparation in periodontology regeneration.
• Advanced PRF (A-PRF): A variant of standard PRF aimed at optimizing the retention of leukocytes and growth factors, although its clinical superiority remains to be confirmed by high-power trials.
• Injectable PRF (i-PRF): Liquid formulation obtained by short centrifugation, allowing for a malleable mass once mixed with biomaterials, thus improving graft handling.
• Titanium-prepared PRF (T-PRF): Uses titanium tubes to influence the fibrin architecture. Current clinical evidence is still too limited to establish superiority over standard PRF.

Clinical results by indication

Intrabony defects represent the indication with the strongest level of evidence. Synthesized data indicate that deep, narrow, and well-contained defects (presenting several bony walls) offer the best prognosis due to increased clot stability. The addition of PRF to surgical procedures shows statistically significant improvements compared to debridement alone. However, the study emphasizes that platelet concentrates do not replace fundamental principles: rigorous root debridement, flap stability, and primary wound closure.

Data analysis and clinical perspectives

This literature review highlights that platelet concentrates, particularly PRF, are emerging as effective adjuvants in the treatment of deep and narrow intrabony defects. Their clinical relevance is based on the release kinetics of growth factors (PDGF, TGF-β, VEGF) and the three-dimensional fibrin matrix that stabilizes the clot. The authors confirm that PRF significantly improves clinical parameters, acting in synergy with bone substitutes to maintain space and promote angiogenesis.

However, the study identifies major methodological limitations. Although the radiographic results of bone filling are encouraging, histological evidence of true periodontal regeneration in humans (new cementum and functional periodontal fibers) remains rare. Furthermore, strong heterogeneity persists in centrifugation protocols (speed, centrifugal force, and duration), which hinders direct comparison of data between different PRF, A-PRF, or T-PRF systems.

Regarding the new formulations, this review notes that the clinical superiority of A-PRF or T-PRF compared to standard PRF is not yet statistically established by high-power trials. i-PRF offers a real ergonomic interest for the preparation of "sticky bone", improving graft handling, but in no way exempts from absolute surgical rigor: meticulous root debridement, flap stability, and primary closure remain the essential pillars of regenerative success.

Summary of results

This review highlights the synergistic action of five key factors (PDGF, TGF-β, VEGF, IGF, EGF) released by platelet concentrates to drive angiogenesis and matrix maturation. While PRF shows significant clinical gains in intrabony defects, the authors point out that the observed radiographic filling should not be confused with true periodontal regeneration, which requires the proven neoformation of cementum, alveolar bone, and functional ligament fibers.

In concrete terms, for the practitioner:

• Simplify your protocols: choose PRF over PRP to eliminate the need for restrictive exogenous activation (thrombin or calcium chloride) and benefit from a natural fibrin architecture.
• Improve handling: use i-PRF to create a "sticky bone", creating a cohesive mass that stabilizes the graft and prevents particle migration in irregular defects.
• Target favorable defects: reserve the intensive use of these concentrates for deep and narrow infra-bony defects, where the regeneration potential is maximal thanks to better clot stability and preserved vascular supply.

Technical lexicon

True periodontal regeneration: A process requiring the simultaneous formation of new cementum, alveolar bone, and functionally oriented periodontal ligament fibers.

Platelet-Rich Fibrin (PRF): Second-generation platelet concentrate prepared without anticoagulants, forming a natural fibrin clot acting as a reservoir for growth factors.

Advanced Platelet-Rich Fibrin (A-PRF): PRF derivative developed to modify the cellular content and handling properties of the concentrate.

Injectable Platelet-Rich Fibrin (i-PRF): Platelet concentrate formulation maintained in liquid form before fibrin polymerization occurs.

Titanium-prepared Platelet-Rich Fibrin (T-PRF): A platelet concentrate variant using titanium tubes during preparation to influence fibrin architecture and biocompatibility.

Fibrin matrix: Three-dimensional network that stabilizes the clot, supports the migration of fibroblasts and endothelial cells, and allows for a gradual release of bioactive mediators.

Intrabony defects: Type of periodontal lesion where the presence of residual bony walls allows for the preservation of blood supply and blood clot stability.

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