Abstract
Chronic rotator cuff tendinopathy is a degenerative condition characterized by persistent shoulder pain, weakness, and functional limitation. Conventional pharmacologic therapies-including nonsteroidal anti-inflammatory drugs and corticosteroid injections-are commonly used but provide only short-term symptom relief without addressing underlying tendon degeneration, and may negatively affect tendon integrity. These limitations have prompted increasing interest in regenerative therapies aimed at promoting tissue repair and durable clinical improvement. This literature review evaluates and compares the clinical outcomes, safety profiles, and practical considerations of regenerative therapies-specifically platelet-rich plasma, mesenchymal stem cell-based interventions, and peptide-based therapies-relative to traditional pharmacologic management for chronic rotator cuff tendinopathy. A comprehensive review of randomized controlled trials, systematic reviews, meta-analyses, and consensus guidelines was conducted to assess pain relief, functional outcomes, tendon structural integrity, safety, and clinical applicability of pharmacologic versus regenerative treatment strategies. Pharmacologic treatments, particularly NSAIDs and corticosteroid injections, demonstrate limited efficacy beyond short-term pain reduction and do not promote tendon healing; repeated corticosteroid use is associated with tendon weakening and inferior long-term outcomes. In contrast, PRP consistently provides superior intermediate- and long-term improvements in pain and function compared with corticosteroids, with favorable safety profiles. Mesenchymal stem cell therapies show promising regenerative potential, including structural tendon improvement and sustained symptom relief, though evidence is limited by heterogeneity, cost, and regulatory constraints. Peptide-based therapies represent an emerging modality with encouraging preclinical and early clinical data but remain insufficiently validated for routine use. Regenerative therapies-particularly platelet-rich plasma and mesenchymal stem cell-based interventions-offer safer and more durable alternatives to conventional pharmacologic management for select patients with chronic rotator cuff tendinopathy who have failed conservative care. However, widespread clinical adoption is limited by variability in protocols, regulatory barriers, and a lack of large-scale, high-quality randomized trials. Further research is required to standardize treatment approaches, refine patient selection, and establish long-term efficacy.