The Platelet-Rich Plasma research ecosystem: From mechanistic insights to precision treatment in knee osteoarthritis

Platelet-rich plasma (PRP) is now one of the most widely used orthobiologics in musculoskeletal medicine, with knee osteoarthritis (KOA) as its main indication. PRP represents a spectrum of autologous preparations with differing cellular and protein content. In this narrative review, we frame current knowledge as a "research ecosystem" spanning mechanistic biology, product characterization, randomized controlled trials (RCTs), systematic reviews and meta-analyses, methodological evaluations, expert consensus, and precision medicine. We highlight the diverse biological roles of PRP components, including the immunomodulatory activity of platelets, the dual regenerative and inflammatory effects of leukocytes, and emerging neutrophil-macrophage crosstalk. Advances in classification systems and deep learning-based quality control are also discussed. Across RCTs, PRP generally outperforms corticosteroids and hyaluronic acid in early to moderate KOA, with benefits lasting several months to a year. Methodological evaluation adds nuance: fragility index analysis confirmed PRP's advantage but showed individual trials were only modestly robust, while spin in systematic reviews often overstated benefits, underscoring the need for more rigorous RCTs and transparent reporting. Leukocyte and platelet concentrations do not explain outcomes, highlighting the importance of patient-specific factors such as metabolic status, inflammation, and structural phenotype. Progress remains hampered by inconsistent reporting, lack of a standardized classification system, and inadequate stratification. We propose a roadmap linking product characterization, standardized reporting, precision patient selection, and objective outcome measures, aiming to shift PRP from a generic injection toward a tailored regenerative therapy.