Potential impact of persistent hyperglycemia on platelet-rich fibrin mediated regeneration of periodontal and peri-implant tissues: Biological mechanisms and clinical implications.

BACKGROUND: Platelet-rich fibrin (PRF) has emerged as a widely utilized autologous biomaterial in periodontal and peri-implant regenerative therapy owing to its ability to provide a three-dimensional fibrin scaffold enriched with platelets, leukocytes, growth factors, and cytokines. However, persistent hyperglycemia (as observed in patients with poorly controlled diabetes mellitus) induces oxidative stress in oral and systemic tissues and impairs angiogenesis and extracellular matrix remodeling. AIM: To provide an overview of the potential impact of persistent hyperglycemia on PRF-mediated regeneration of periodontal and peri-implant tissues, and to gain an in-depth understanding of the underlying biological mechanisms and their clinical implications. MATERIALS AND METHODS: The research question was "Does a state of persistent hyperglycemia affect PRF-mediated periodontal and peri-implant tissue regeneration?" Indexed databases and Google Scholar were searched without time and language barriers up to and including August 2026. The pattern of the present study was customized to summarize the pertinent studies. RESULTS: Evidence evaluating the impact of persistent hyperglycemia on PRF remains limited and is largely confined to ex vivo, in vitro, and observational studies. Nevertheless, the available data consistently suggest that poorly controlled diabetes mellitus is associated with alterations in PRF architecture, including increased porosity, reduced clot dimensions, diminished PRF yield, and a less organized fibrin meshwork. Limited evidence also indicates that although growth factor release from PRF may be preserved under hyperglycemic conditions, PRF obtained from individuals with well-controlled diabetes mellitus shows structural and biological characteristics that closely resemble those observed in systemically healthy individuals. This suggests that regenerative capacity may be preserved when glycemic levels are adequately controlled. This supports the idea that the regenerative capacity of PRF may be preserved when glycemic levels are adequately maintained. CONCLUSIONS: Glycemic control appears to be a key determinant of PRF quality and regenerative outcomes. Nevertheless, the lack of prospective clinical studies evaluating direct regenerative outcomes highlights the need for well-designed clinical trials to clarify the influence of persistent hyperglycemia on PRF-mediated periodontal and peri-implant regeneration. CLINICAL RELEVANCE: Persistent hyperglycemia may compromise the regenerative potential of PRF primarily through alterations in fibrin architecture, which may further lead to faster clot breakdown and impairment of biological responsiveness within a chronically inflammatory environment. However, limited data to date suggest that effective glycemic control and patient education may help preserve PRF characteristics favorable for periodontal and peri-implant tissue regeneration.