Recent advances in piezoelectric hydrogels for osteoarthritis therapy: material design, signal transduction, and clinical translation

Abstract

With no disease-modifying therapy available, osteoarthritis (OA) remains a primary cause of disability worldwide. However, between 2023 and 2026, rapid advances have been made in the development of piezoelectric hydrogels, a technology that transduces joint motion into endogenous electrical signals, thereby restoring the electromechanical microenvironment of degenerated cartilage. This short review provides a critical synthesis of these developments through a four-dimensional framework encompassing material design, signal transduction, therapeutic efficacy, and translational validation. Three material design paradigms are analysed: inorganic nanofiller composites, organic piezoelectric polymers, and natural biopolymer hydrogels. This analysis reveals that the central unresolved controversy is the fundamental trade-off between piezoelectric output and biointegration. The Ca2+–TRPV4/Piezo1–MAPK/ERK–SOX9 signalling cascade is the core anabolic pathway, complemented by M1-to-M2 macrophage polarisation and NLRP3 inflammasome inhibition. Although preclinical evidence from small-animal OA models has demonstrated consistent International Cartilage Repair Society (ICRS) score improvements, three critical research gaps persist: the absence of validation in spontaneous or metabolic OA models, the lack of long-term efficacy data beyond 12 weeks, and inadequate characterisation of the decline in piezoelectric performance under physiological conditions. This review highlights emerging synergistic strategies combining piezoelectric hydrogels with ultrasound or magnetic field stimulation to overcome motion-dependent output instability, and identifies adaptive piezoelectric design, multimodal physical stimulation integration, and functional reconstruction–centred evaluation as key priorities for clinical translation.