Electrically Conductive and Mechanoactive Scaffolds Synergistically Enhance Osteogenic Cell Responses Upon Mechanical Stimulation

Abstract

Bone is a dynamic tissue that responds to mechanical forces and possesses intrinsic mechanoelectrical activity.Recently, electrically conductive materials have emerged as promising biomaterials for bone tissue engineering. This study presents the development of electrically conductive, mechanoactive porous scaffolds for bone tissue engineering, by incorporating two concentrations of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) into a matrix comprising poly(vinyl alcohol) (PVA) and gelatin (Gel). Material testing revealed that scaffolds with the highest PEDOT concentration exhibited higher electrical conductivity, increased porosity, and an enhanced Young modulus of 2.6±0.3 MPa compared to the PVA/Gel control. Pre-osteoblastic cells cultured within the conductive, mechanoactive scaffolds under uniaxial compression showed increased cell viability, calcium influx, and upregulation of osteogenic markers. Dynamic cultures enhanced the activation of the mechanotransduction receptors YAP/TAZ, and promoted the alkaline phosphatase expression, collagen secretion, and calcium deposition, particularly in higher concentration PEDOT-containing scaffolds, with hydroxyapatite formation on day 21. The results signify a synergistic effect of conductive, mechanoactive scaffolds on the osteogenic cell responses under mechanical stimulation, which can be attributed to the activation of mechanosensitive ion channels that elevated the calcium ion influx. In vivo subcutaneous implantation of the developed scaffolds for two weeks in mice indicated lack of any adverse immune responses. These results highlight the great potential of electroactive, mechanoresponsive scaffolds as biomimetic substrates to enhance osteogenesis under mechanical stimulation.

Keywords: Dynamic cell culture, electrically conductive polymer, Mechanotransduction, mechanoactive, bone formation, PEDOT:PSS