The use of PRF in periodontal plastic surgery has introduced a biologically driven approach to soft tissue management that complements or, in selected cases, substitutes traditional autologous grafts. Unlike CTGs, which involve additional surgical morbidity and longer postoperative recovery, PRF offers the advantage of being minimally invasive, autologous, and rich in growth factors conducive to tissue regeneration.

One of the central strengths of PRF lies in its multifunctional biological profile. Beyond acting as a scaffold, PRF serves as a delivery system for a broad spectrum of cytokines and growth factors, including PDGF, TGF-β, and VEGF, which orchestrate key events in wound healing, such as fibroblast migration, angiogenesis, and extracellular matrix remodeling. These biologic effects are most pronounced in i-PRF, which has demonstrated enhanced ability to stimulate gene expression related to collagen synthesis and cellular proliferation in vitro.

In addition to its biological activity, PRF's ease of application and autologous origin render it particularly appealing in patients for whom donor site surgery is contraindicated or undesirable. The absence of donor site morbidity, combined with patient-reported reductions in pain and surgical trauma, supports its growing popularity in esthetically driven mucogingival therapy. However, PRF is not a universal replacement for CTG. In clinical scenarios requiring maximal KTW or CRC, CTG remains the superior approach due to its long-term stability and volume retention.

An important and increasingly recognized use of PRF is as a healing adjunct at the palatal donor site during CTG procedures. When a CTG is required, applying PRF to the exposed donor area can significantly accelerate soft tissue healing, reduce inflammation, and improve patient comfort. This approach is especially valuable in cases involving thin palatal mucosa, multiple graft harvests, or patients with low pain tolerance. PRF can serve as a protective biologic dressing, enhancing epithelialization while minimizing postoperative bleeding and discomfort. Its hemostatic and anti-inflammatory properties, coupled with its capacity to promote angiogenesis, make it a reliable aid in reducing donor site morbidity and facilitating faster recovery.

A critical consideration emerging from the literature is the variability in PRF preparation protocols. The final biological composition of PRF is highly dependent on centrifugation speed, time, rotor type, and tube material. These factors directly influence the number of platelets and leukocytes retained, the density of the fibrin matrix, and the release kinetics of bioactive molecules. For example, the LSCC and horizontal centrifugation have been associated with improved cellular yield and growth factor concentration compared to traditional protocols. Inconsistencies in preparation may account for the heterogeneity of clinical outcomes observed across studies, emphasizing the need for standardized, reproducible techniques.

Furthermore, while several in vitro studies have demonstrated the biological plausibility of PRF in enhancing soft tissue regeneration, the translation of these findings to predictable clinical outcomes remains an area requiring further investigation. Many studies are limited by small sample sizes, short follow-up periods, or lack of histologic verification. The heterogeneity in study designs, outcome measures, and PRF formulations complicates the ability to conduct high-level meta-analyses and restricts the generalizability of current evidence.

Emerging formulations such as advanced PRF (A-PRF), horizontal PRF (H-PRF), and PRF combined with bioactive agents like hyaluronic acid (CHA-PRF) show promise in enhancing regenerative outcomes. These innovations highlight a trend toward optimizing both the biological and mechanical properties of PRF, potentially expanding its indications in periodontal and peri-implant soft tissue applications. However, robust clinical trials comparing these novel formulations against established therapies are still lacking.

Overall, while PRF cannot fully replace autogenous grafts in all periodontal plastic procedures, its versatility, biocompatibility, and patient-centered benefits warrant serious consideration. As the field advances, greater emphasis on methodological consistency, long-term outcome data, and patient-reported experiences will be essential to fully define PRF's role in contemporary periodontal therapy.

Limitations
While the clinical and biological data supporting the use of PRF in periodontal plastic surgery are promising, several limitations must be acknowledged. First, variability in PRF preparation protocols, including differences in centrifugation speed, rotor type, temperature control, and tube material, introduces significant heterogeneity across studies (Dohan Ehrenfest et al., 2018). This lack of standardization makes it difficult to draw definitive conclusions about the efficacy of one PRF protocol over another or to compare outcomes directly between studies.

Second, many of the available RCTs suffer from small sample sizes and short follow-up periods, often limited to 6 or 12 months. Long-term stability of soft tissue gains achieved with PRF, especially in the context of gingival recession coverage, remains insufficiently documented (Miron et al., 2020; Barootchi et al., 2025). Similarly, most clinical trials have not included histological analyses to confirm the quality of regenerated tissue, leaving uncertainty regarding the true regenerative capacity of PRF-based therapies.

Another limitation is the absence of consistent patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in many studies. Although PRF is frequently associated with lower morbidity and improved comfort, quantifiable evidence of these benefits is still limited in scope and often reliant on visual analog scales without further qualitative analysis (Moraschini & Barboza, 2016).

Finally, while in vitro studies such as those by [4,9] offer mechanistic insights into PRF’s cellular and molecular effects, translating these findings into predictable clinical outcomes requires further validation through well-controlled in vivo studies and multicenter RCTs.