Localized Hydrogel Microspheres for Osteoarthritis Treatment: Recruitment and Differentiation of Stem Cells

Abstract

Osteoarthritis (OA) represents a common degenerative joint disorder marked by progressive cartilage degradation, necessitating innovative therapeutic approaches beyond symptom management. Here, this study introduces a novel strategy leveraging the regenerative capabilities of mesenchymal stem cells (MSCs) by utilizing a bioactive extracellular matrix (ECM) derived from IFN‐γ‐stimulated MSCs, encapsulated within aldehyde‐ and methacrylic anhydride‐modified hyaluronic acid hydrogel microspheres (AH). This engineered scaffold effectively mimics the native cartilage microenvironment, promoting targeted adhesion and retention at damaged sites via spontaneous Schiff base reactions. Notably, the IFN‐γ‐ECM@AH microspheres facilitate the localized release of key chemokines, such as CXCL12, enhancing endogenous stem cell recruitment, and bioactive factors (e.g., TGF‐βI and TGF‐β3) to drive chondrogenic differentiation. Additionally, the scaffold possesses binding sites for cellular integrins, further augmenting the regenerative potential of stem cells. Collectively, the approach presents a dual‐action mechanism that supports efficient cartilage repair and regeneration, positioning this engineered microenvironment as a promising therapeutic avenue for OA and potentially other degenerative conditions.