Piezoelectric Accelerated Tissue Engineering Using HA Nanoparticle Embedded Nature Protein-Based Coaxial Nanomembrane

Amidst problems associated with the aging population, addressing fracture patients with poor bone quality associated with the loss and deformation of cellular matrix proteins has been a major challenge. Recently, nanofibers have attracted significant attention as substrates that mimic the structural microenvironment of the native extracellular matrix. Despite their morphological advantages, nanofiber-based tissue engineering therapies limit electric signaling pathways that control cell-to-cell physiological interactions. Here, we exploit piezoelectric protein-based coaxial nanofibers enhanced by the alpha-helix to beta-sheet transition to produce appropriate bioelectrical signals, which provide electroactivity for matrix production <i>via</i> cell growth and proliferation. The coaxial nanofiber is composed of a hydroxyapatite (HA) nanoparticles-embedded piezo-protein shell and a polycaprolactone (PCL) core with simvastatin (SIM). Gradual biodegradation of the protein reveals HA nanoparticles, which support adhesion of proteins and involvement in cell differentiation with mineralization, while continuous release of SIM assists the rapid growth of HA. The designed beta-sheet protein shell/PCL core nanofibers are promising candidates for tissue engineering and mechanoelectrical transduction platform due to their phased functionality in electrophysiological activity, biodegradability, HA nucleation, and mineralization. Overall, the proposed strategy has the potential to meet the challenging requirements in inducing rapid tissue function reconstruction. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1C1C2011542) and NRF-2017-Fostering Core Leaders of the Future Basic Science Program/Global Ph.D. Fellowship Program.