Electrically conductive and mechanoactive scaffolds synergistically enhance osteogenic cell responses under mechanical stimulation

Bone is a dynamic tissue that responds to mechanical forces and possesses intrinsic mechanoelectrical activity. Recently, electrically conductive polymers have emerged as stimulating biomaterials for bone tissue engineering. However, the effect of conductive scaffolds under mechanical stimulation towards bone formation remains unclear. This study presents the development of electrically conductive, mechanoactive porous scaffolds, and the validation of their osteogenic capacity under mechanical stimulation. The developed scaffolds contain poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) into a double polymeric network comprising poly(vinyl alcohol) (PVA) and gelatin (Gel). PEDOT-containing scaffolds demonstrated superior electrical conductivity, increased surface porosity, and an elevated Young modulus of 2.7 ± 0.4 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. Mechanical loading enhanced the activation of the mechanotransduction markers YAP/TAZ, upregulated alkaline phosphatase activity, collagen secretion, and calcium deposition, particularly in PEDOT-containing scaffolds, with hydroxyapatite formation on day 21. <i>In vivo</i> subcutaneous implantation of the developed scaffolds indicated lack of any adverse immune responses. These results highlight the great potential of the developed electroactive, mechanoresponsive scaffolds as biomimetic substrates to enhance osteogenesis under mechanical stimulation.