Dual-loaded BMSCs-Metformin microgels promote cartilage repair through combined anti-inflammatory, antioxidant, and regenerative effects.

Abstract

The restricted self-healing capacity of articular cartilage, combined with the inflammatory response and oxidative stress that follow injury, makes articular cartilage restoration a challenging therapeutic problem. We engineered an injectable porous microgel system (BMSC-Met@MGs) utilizing microfluidic technology comprising GelMA, CSMA, and PVA, which co-encapsulate bone marrow mesenchymal stem cells (BMSCs) and metformin via hydrogen-bonded sustained release. This structure uniquely integrates immune modulation (downregulation of MMP3/MMP13), antioxidation (clearance of reactive oxygen species and restoration of the mitochondrial membrane potential), and cartilage regeneration (upregulation of COL2A1) in vitro. Preliminary in vivo results suggest that BMSC-Met@MGs facilitated hyaline cartilage repair in rats. Our study introduced a comprehensive therapeutic approach with anti-inflammatory, antioxidant, and regenerative effects, marking the inaugural use of metformin in the repair of cartilage defects. This synergistic material/drug/cell method offers novel insights into cartilage repair.