Development and Utilization of Piezoelectric Scaffold Systems for the Modulation of the Physico-Chemical Microenvironment of the Cells to Enhance Their Regenerative Behaviors

Author(s): Ico, Gerardo | Advisor(s): Nam, Jin | Abstract: Piezoelectric polymer, poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)), exhibits excellent characteristics, such as flexibility and biocompatibility, for various biological applications that utilize energy conversion between mechanical strain and electric potentials. However, its typically low piezoelectric properties have limited its use as an effective piezoelectric platform. To address this, electrospinning was utilized as a method to manipulate the nanostructure of P(VDF-TrFE) nanofibers to engineer a high-performing piezoelectric material. More specifically, we show that the piezoelectric performance of P(VDF-TrFE) is size dependent; by dimensional reduction to the nanoscale (30 nm), a transformative enhancement in piezoelectric performance was achieved by the synergistic effects of flexoelectricity materialization and enhanced dipole domain alignment. The electrospun P(VDF-TrFE) at this size scale exhibits an exceptional piezoelectric coefficient, d33, at -108 pm V-1, approaching the same magnitude of more traditional inorganic materials, while maintaining its flexibility.We exploit these high performing P(VDF-TrFE) nanofibers for specific biological applications. In one aspect, the large surface area-to-volume ratio inherent to nanomaterials, together with the transformative piezoelectric properties, allowed us to use the material as an ultrasensitive, acoustic-responsive, drug delivery platform driven by the direct piezoelectric effect. The intrinsic negative zeta potential was utilized to electrostatically load cationic drug molecules. We show that the drug release sensitivity of the P(VDF-TrFE) nanofibers depends on the fiber diameter, thus piezoelectric properties. We further showed that the drug release quantity can be tuned by applied acoustic pressure or number of acoustic doses for specific tissue applications. Additionally, through the direct piezoelectric effect, we also demonstrated the utility of P(VDF-TrFE) nanofibers with an aligned morphology in neural tissue engineering. We demonstrate that the piezoelectric P(VDF-TrFE) nanofibers provide a means to culture neural stem cells while electrically stimulating the cells by acoustic actuation of the scaffold, generating electric potentials that were utilized to modulate the cellular behaviors. The electrical stimulation of neural stem cells resulted in neural stem cell differentiation towards different phenotypes, including neurons, oligodendrocytes, and astrocytes, demonstrating the potential utility of the piezoelectric scaffolds for engineering neural tissues composed of multiple cell phenotypes.Finally, a proof-of-concept cell culture platform that can modulate the mechanical properties of cell culture scaffolds on demand, was devised based on the indirect piezoelectric effect. Microfabricated interdigitated electrodes were designed, via computational simulations, to act as an electric field-generating substrate for the P(VDF-TrFE) scaffold. We showed that the stiffness of the P(VDF-TrFE) nanofibers electrospun onto such interdigitated electrodes can be precisely controlled by modulating the applied electric fields across the electrodes. The results demonstrate the significant potential of electrospun piezoelectric nanofibers for a cell culture substrate with an on-demand change of the physical cellular microenvironment.