Slide-Ring Structured Stress-Electric Coupling Hydrogel Microspheres for Low-Loss Transduction Between Tissues.

High transductive loss at tissue injury sites impedes repair. The high dissipation characteristics in the electromechanical conversion of piezoelectric biomaterials pose a challenge. Therefore, supramolecular engineering and microfluidic technology is utilized to introduce slide-ring polyrotaxane and conductive polypyrrole to construct stress-electric coupling hydrogel microspheres. The molecular slippage mechanism of slide-ring structure stores and releases mechanical energy, reducing mechanical loss, the piezoelectric barium titanate enables stress-electricity conversion, and conjugated π-electron movement in conductive network improves the internal electron transfer efficiency of microspheres, thereby reducing the loss in stress-electricity conversion for the first time. Compared to traditional piezoelectric hydrogel microspheres, the stress-electric coupling efficiency of low-dissipation microspheres increased by 2.3 times, and the energy dissipation decreased to 43%. At cellular level, electrical signals generated by the microspheres triggered Ca2+ influx into stem cells and upregulated the cAMP signaling pathways, promoting chondrogenic differentiation. Enhanced electrical signals induced macrophage polarization to the M2 phenotype, reshaping inflammation and promoting tissue repair. In vivo, the low-dissipation microspheres restored low-loss transduction between tissues, alleviated cartilage damage, improved behavioral outcomes, and promoted the treatment of osteoarthritis in rats. Therefore, this study proposes a new strategy for restoring low-loss transduction between tissues, particularly in mechanically sensitive tissues.