Injectable and Biodegradable Piezoelectric Hydrogel for Medical Applications

Osteoarthritis (OA), a painful joint disease manifested by cartilage damage, affects 654 million people worldwide every year. Currently, there is no cure for OA; available medicines only alleviate the disease symptoms (e.g. pain and inflammation) while surgical approaches including the use of replacement auto- or allo- graft cartilages suffer from the problems of donor-site morbidity, infection, immune-rejection, and especially, limited tissue supply. Herein, we present a novel injectable and biodegradable piezoelectric hydrogel with ultrasound (US) activation to offer a minimally invasive regenerative engineering approach for OA treatment. The piezoelectric hydrogel can be injected into the joints and self-produce localized electrical cues under US activation to drive cartilage healing. <i>In vitro</i> data shows the hydrogel with US activation attracts host cells, enhances cell migration, and induces stem cells to secrete endogenous growth factors like TGF-β1 which facilitates <i>COL2A1</i>, <i>ACAN</i>, and <i>SOX9</i> expression to promote chondrogenesis and extracellular matrix (ECM) deposition. Significantly, the piezoelectric hydrogel enables the healing of hyaline cartilage in rabbits with critical size osteochondral defects. After two months of the piezoelectric hydrogel and US treatment, the animals had more subchondral bone formation, well-organized hyaline cartilage structure, and improved mechanical properties, close to those of healthy native cartilages and superior to the other control/sham groups either without US activation or piezoelectricity. This injectable piezoelectric hydrogel is not only applicable for cartilage healing but potentially other tissue regeneration and could serve as a minimally-invasive material platform for important medical devices such as injectable piezoelectric pressure sensors, actuators, energy-harvesters, and transducers, thus offering a significant impact on medicine.