Conductive Hyaluronic Acid/Chitosan Scaffold Obtained by Sustainable Phase Separation: A Candidate for Tissue Engineering

Conductive polymers are increasingly studied in tissue engineering. Even without electrical stimulation, they significantly improve cell adhesion and growth. In this study, we report the preparation of conductive hyaluronic acid/chitosan (HA/CHI) scaffolds using salinity change-induced aqueous phase separation, followed by a cross-linking (CRL) step and poly(3,4)ethylene-dioxythiophene (PEDOT) functionalization. HA/CHI were mixed in a concentrated NaCl solution to prevent their complexation. A polysaccharide-based scaffold was formed by immersing a millimeter-thick volume of the HA/CHI mixture solution in pure water. The scaffold was then further cross-linked and functionalized with PEDOT to produce mechanically strong and electrically conductive HA/CHI scaffolds that support enhanced cell colonization. The resulting microporous PEDOT-(HA/CHI)CRL scaffold has a porosity of 73% and an average pore size of 44 ± 15 μm. It exhibits a storage modulus of 15 kPa and a conductivity of 1.5 ± 0.3 × 10–5 S/cm. Unlike the HA/CHI and (HA/CHI)CRL scaffolds, NIH3T3 fibroblasts adhere to, grow on, and colonize the conductive scaffold within 14 days. Compared to traditional methods, the salinity change-induced aqueous phase separation technique does not require complex equipment and consumes less energy. This method shows great potential for creating sustainable scaffolds for tissue engineering.