Precise Cell Type Electrical Stimulation Therapy Via Force-electric Hydrogel Microspheres for Cartilage Healing.

Electrical stimulation enhances cellular activity, promoting tissue regeneration and repair. However, specific cells and maintaining a stable energy supply are challenges for precise cell electrical stimulation therapy. Here, force-electric conversion hydrogel microspheres (Piezo@CR MPs) is devloped to induce specific stem cell aggregation and promote chondrogenic differentiation through localized electrical stimulation. These MPs contain barium titanate (BT) nanoparticles embedded in hyaluronic acid methacrylate hydrogel MPs, with a polydopamine (pDA) coating bound to stem cell recruitment peptides (CR) via π-π conjugation and electrostatic forces. Piezo@CR MPs convert pressure (ultrasound) into electrical stimulation, directing BMSCs for colonization and chondrogenesis. In vitro, directionally migrated stem cells almost covered the Piezo@CR MP surface, generating up to 451 mV of electrical output that enhanced chondrogenic differentiation. In a rabbit osteochondral defect model, Piezo@CR MPs promoted cartilage regeneration, nearly resembling native cartilage. In a rat osteoarthritis model, they reduced cartilage degeneration and improved behavioral outcomes. Additionally, Piezo@CR MPs promoted cartilage regeneration by driving the influx of extracellular calcium and activating the p38 mitogen-activated protein kinase (MAPK) pathway. In conclusion, Piezo@CR MPs offer a new approach for precise cell type electrical stimulation therapy in treating of cartilage injuries and degeneration.