Mineralization Stimuli of Hydroxyapatite-Embedded Hierarchical Nanofibrous Scaffold Using Piezoelectric Protein for Tissue Engineering

The development of novel biomaterials that provide electrical potentials generated through bioactive scaffolds with respect to their appropriate effects on cell behaviors is essential for tissue engineering. In particular, piezoelectric biomaterials are attractive due to the possibility to produce electrical potentials for stimulation via cell motility. Despite their capacity to promote tissue regeneration through cell stimulation, synthetic piezoelectric biomaterials still face issues with poor biocompatibility and inflammatory response. Here, we designed a scaffold that supports cellular activity without eliciting any toxic effect on the host immune response by using a nature-derived piezoelectric protein and mimicked extracellular matrix microenvironment topologies using electrospinning to enhance cell adhesion. The scaffold enhanced piezoelectricity to overcome limited electrical signaling pathways of the nanofibrous membrane via alpha-helix to beta-sheet transition, and this led to elevated mechanical properties and wettability according to the morphological modification. In addition, the hierarchical structure of the scaffold induced a sequential release of hydroxyapatite and simvastatin by gradual biodegradation of the protein to accelerate homogenous growth in a higher local ion concentration during mineralization. Our scaffold is a promising candidate for tissue engineering and mechanoelectrical transduction platform due to its phased functionality in electrophysiological activity, biodegradability, and mineralization. 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.