Platelet-rich plasma and knee osteoarthritis: A critical overview of the multiple biases and methodological complexity.

Intra-articular injections of platelet-rich plasma (PRP) are increasingly utilized in the management of knee osteoarthritis (KOA) and various other medical specialties. However, the efficacy of PRP remains a contentious issue; some experts consider it to be a placebo, while others advocate for its therapeutic value. Evidence from controlled clinical trials and meta-analyses has often yielded contradictory results, frequently failing to demonstrate a clear clinical benefit despite favorable outcomes observed in real-world settings. Several factors may contribute to these inconsistencies, with the lack of standardization in PRP preparation and the heterogeneity of KOA phenotypes being the most significant. Phenotyping is more effectively accomplished in specialized clinical environments, which may elucidate the improved outcomes associated with better patient selection. After delineating the specific characteristics of PRP injections and the primary sources of variability, we emphasize the necessity for comprehensive characterization of the injected product and accurate phenotyping of KOA. Additionally, we examine the methodological biases that impede the interpretation of clinical results and propose a treat-to-target approach as a more suitable evaluation strategy. These methodological challenges should not undermine the potential of regenerative medicine, which offers considerable promise. Compared to conventional therapies, regenerative medicine is generally more compatible with human physiology, better tolerated, and potentially less expensive. However, the advancement of this field necessitates strict scientific rigor and objectivity. This involves a meticulous recognition of biases and methodological limitations, as well as a deeper understanding of the underlying mechanisms of action, to refine and optimize therapeutic protocols.