Individual and combinatorial effects of stiffness and electrical conductivity on host-immune responses to conductive hydrogels

Abstract Electrically conductive hydrogels (ECHs) with mechanical softness and electrical conductivity are promising materials for biomedical engineering applications, e.g., tissue engineering and bioelectronics. However, the effects of the mechanical and electrical properties of ECH on the immune system remain unexplored. Thus, we prepared several graphene oxide-incorporated polyacrylamide hydrogels with varying stiffnesses and conductivities, and examined their interactions with macrophages and host tissues in vitro and in vivo. Stiff ECHs can reduce the pro-inflammatory cytokine levels and increase the anti-inflammatory marker expression in the acute phase, however, it eventually causes severe inflammation, regardless of the conductivity. In contrast, ECH conductivity generally attenuated inflammation and affected fibrotic collagen deposition depending on stiffness. Overall, high-conductivity soft ECHs exhibited the lowest inflammatory reactions, and high-conductivity rigid ECHs provided the greatest acceleration of fibrous collagen encapsulation. The present findings provide vital insights for the future development of hydrogel-based electronics and electroactive tissue-engineering scaffolds.