Platelet-rich plasma - A comprehensive review of isolation, activation, and application

Platelets and platelet enriched products have been widely studied for their roles in promoting cell proliferation, migration, and tissue regeneration, making them highly interesting for clinical applications such as traumatology, dental, orthopaedic, and plastic surgery. However, their clinical adoption remains limited, partly due to fragmented and inconsistent data. Previous reviews have explored various applications of PRP therapies, but no comprehensive work has systematically mapped their processing methods, treatment modalities, and applications alongside clinical outcomes. This review thus aims to provide a thorough analysis of platelet-rich products, including platelet-rich plasma and platelet lysate, critically assessing their therapeutic potential. Variability in factors such as platelet and leukocyte content, red blood cell contamination, and activation methods complicates the clinical implementation and standardization of platelet-rich products. Herein, we examine platelet structure, function, and growth factors (e.g., PDGF, VEGF, and TGF-β) essential for tissue repair and regeneration, alongside manufacturing processes and isolation techniques impacting product quality. Additionally, we explore platelet recovery, activation strategies (chemical, physical, enzymatic), application forms, patient-related variables, and the immune-modulatory roles of platelets in inflammation, wound healing, and immune response regulation. Our findings highlight the urgent need for standardized protocols to improve consistency and efficacy of platelet-derived products, providing a framework to guide readers in selecting adequate procedures for specific clinical indications or research applications. STATEMENT OF SIGNIFICANCE: Platelet-rich plasma (PRP) has gained widespread attention for its regenerative potential, but its clinical outcomes remain inconsistent due to variability in preparation and application methods. This comprehensive review critically synthesizes the full PRP pipeline-from donor selection and processing to activation strategies and delivery modalities-highlighting key sources of heterogeneity. By integrating current evidence across disciplines, we provide a unified framework for optimizing PRP use in musculoskeletal repair and beyond. This work addresses a major knowledge gap and offers a timely resource for clinicians and researchers aiming to harness PRP more effectively.