Abstract
Background/Objectives: Regenerative therapies have gained interest in orthopedic applications for their potential to enhance tissue regeneration, functional recovery, and pain modification. This review evaluates the clinical efficacy of platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), peptide-based treatments, and biomimetic materials in orthopedic care, with a focus on pain reduction and functional outcomes. Methods: A structured literature search in PubMed (January 2009-January 2025) identified 160 studies. After applying inclusion criteria prioritizing randomized controlled trials (RCTs) and clinical trials, 59 studies were included: 20 on PRP, 20 on MSCs, 10 on peptide therapies, and 7 on biomimetics. Data extraction focused on pain reduction and functional recovery, with risk of bias assessed using the Cochrane Risk of Bias (RoB) tool and ROBINS-I tool. A random-effects meta-regression analysis was conducted to evaluate the impact of therapy type, sample size, and risk of bias on reported pain reduction outcomes. Results: Meta-regression analysis identified MSC therapy as the most effective intervention for pain reduction (β = 8.45, p < 0.05), with PRP and peptide-based therapies showing moderate improvements, and biomimetic therapies demonstrating the lowest effect. PRP provided short-term pain relief, particularly in acute injuries and tendon repair, though inconsistencies in preparation methods limited success in chronic conditions. MSC therapies demonstrated cartilage regeneration and early osteoarthritis improvement, but high costs and ethical concerns remain barriers to widespread adoption. Peptide-based therapies and biomimetic materials, including engineered scaffolds and autologous protein solutions, showed promise for infection control and wound healing, though further research is needed to optimize dosing, delivery methods, and long-term safety. Conclusions: Regenerative therapies offer significant potential in orthopedic care, with MSC therapies demonstrating the most reliable regenerative effects, PRP providing short-term symptomatic relief, and peptide-based and biomimetic treatments emerging as promising adjuncts. However, standardized protocols and large-scale clinical trials are needed to establish long-term efficacy and improve clinical translation for broader adoption.