Immunomodulatory Strategies for Cartilage Regeneration in Osteoarthritis.

Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability globally. While many efforts have been made to treat this condition, current tissue engineering and regenerative medicine strategies fail to address the inflammatory tissue environment that leads to the rapid progression of the disease and prevents cartilage tissue formation. First, this review addresses in detail the current anti-inflammatory therapies for OA with a special emphasis on pharmacological approaches, gene therapy and MSC intra-articular administration, and discusses the reasons behind the limited clinical success of these approaches at enabling cartilage regeneration. Then, we analyse the state-of-the-art tissue engineering strategies and how they can be improved by incorporating immunomodulatory capabilities such as the optimization of biomaterial composition, porosity and geometry, and the loading of anti-inflammatory molecules within an engineered structure. Finally, the review discusses the future directions for the new generation of tissue engineering strategies for OA treatment, specifically focusing on the spatio-temporal modulation of anti-inflammatory agent presentation to allow for tailored, patient-specific therapies.