Precise Cell Type Electrical Stimulation Therapy Via Force‐electric Hydrogel Microspheres for Cartilage Healing
Zeyu Han, Fan Wang, Wei Xiong, Meng Chen, Yubin Yao, Wenguo Cui, Mingzhu Zhang
Abstract
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.