Biodegradable Piezoelectric Nanofibers for Tissue Regenerative Engineering

Every year, millions of Americans suffer from bone and cartilage diseases like osteoarthritis. Artificial “engineered” bone and cartilage grafts constructed <i>in vitro</i> by using synthetic biomaterial scaffolds – have received considerable attentions. Yet, the constructed tissues often rely on potentially toxic growth factors and/or seeded stem cells which pose risks of immune rejection, limited supplies and undesired cell differentiation into cancers. Alternative to the biochemical factors, electrical cues can be used as a safe and effective stimulation for tissue regeneration. Herein, for the first time, we present a cell-free and growth factor-free biodegradable piezoelectric (poly (L-lactic acid)) (PLLA) nanofiber scaffold which under applied force can act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. We have reported the piezoelectric tissue scaffold and the piezoelectric PLLA in several journals of Science Translational Medicine, PNAS and Nano Energy (Science Transl. Med. 14, (627), eabi7282, 2022; PNAS 117.1 (2020): 214-220, PNAS 115.5 (2018): 909-914, and Nano Energy 76 (2020): 105028.). The PLLA scaffold with applied force can generate piezoelectric charge to significantly improve chondrogenic effect of adipose stem cells <i>in vitro</i>. Rabbits conditioned with critical-sized osteochondral defects and receiving piezoelectric scaffold + exercise treatment showed a significant hyaline-cartilage regeneration with completely healed cartilages that exhibit abundant chondrocytes and collagen type II. The hybrid biodegradable piezoelectric scaffold/stimulator system, presented herein, could be used to not only heal cartilage but also bone, nerve, muscle etc. without the need of invasive removal process, offering a significant impact on the field of tissue regenerative engineering.