Intra-articular therapies for synovial joint dysfunction: a comprehensive integrative review

To summarize contemporary evidence for intra-articular therapies in synovial joint dysfunction-emphasizing temporomandibular joint (TMJ) osteoarthritis-across regenerative (platelet-rich plasma [PRP]/ injectable platelet-rich fibrin [i-PRF], mesenchymal stem cells), lubricating (hyaluronic acid [HA]), anti-inflammatory (corticosteroids), and selected adjunctive/combination approaches.

An integrative narrative review (2020-2025) was performed of randomized trials, systematic reviews/meta-analyses, and high-quality mechanistic/preclinical studies (PubMed/Scopus/Web of Science/SciELO; English/Portuguese/Spanish). Quality considerations followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidance, Mixed Methods Appraisal Tool, and Cochrane/risk of bias paradigms; TMJ-specific data were prioritized with biologically justified extrapolation from other synovial joints.

Mesenchymal stem cells yield visual analog scale reductions ≈30%-50% and Western Ontario and McMaster Universities Arthritis Index gains ≈20%-40% with reassuring 2-year safety and synergy when paired with HA/PRP. PRP improves symptoms ≈3-6 months but is preparation-sensitive; i-PRF's fibrin matrix sustains bioactive release (7-14 days), shifts synovial cytokines (interleukin [IL]-1β ↓58%, IL-6 ↓63%, IL-17 ↓51%, IL-10 ↑3-5×), and is associated with magnetic resonance imaging chondral preservation and larger clinical effects in TMJ/temporomandibular disorders. HA (especially high-molecular weight or cross-linked, bacterial-derived) consistently reduces pain 25%-45% with outstanding safety. Corticosteroids offer 50%-70% short-term relief but carry dose-dependent chondrotoxicity. Adjuncts (botulinum toxin type A, dextrose, ozone) and combinations (i-PRF+HA/ozone) are promising.

Intra-articular therapy has advanced from palliation to mechanism-driven modulation. i-PRF and mesenchymal stem cells show the strongest disease-modifying signals; HA remains a safe backbone and carrier. Standardized preparation/ reporting and TMJ-focused randomized trials are priority needs.