Conductive Microgel Annealed Scaffolds Enhance Myogenic Potential of Myoblastic Cells.

Abstract

Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel-based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. Conductive microgels aregenerated from poly(ethylene) glycol (PEG and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT: PSS increasesmicrogel conductivity two-fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibitincreases in the late-stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, isinfluenced only by porosity. Human skeletal muscle-derived cells exhibitincreased Myod1, insulin like growth factor-1, and insulin-like growth factor binding protein 2 at earlier time points on conductive microgel scaffolds compared to non-conductive scaffolds. They also secretemore vascular endothelial growth factor at early time points and expressfactors that led to macrophage polarization patterns observe during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.