Electroconductive Antibacterial Bioinks Enable Electrical Stimulation Enhancement of Proliferation and Elongation of Human Skin Fibroblasts

Abstract

The limited electrical conductivity and poor antibacterial performance of many existing bioinks hinder their effectiveness in wound healing applications, where mimicking the native electrical properties of skin and preventing infection are critical. In this study, we developed multifunctional electroconductive and antibacterial bioinks designed to work synergistically with electrical stimulation (ES) therapy to overcome these limitations. These new bioinks are formulated by integrating the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) into a carboxymethyl cellulose (CMC) and alginate (ALG) biopolymer matrix, followed by ionic cross-linking using Ga³⁺ ions. The CMC/ALG network provided favorable rheological properties for 3D bioprinting, while PEDOT:PSS imparted electrical conductivity to the resulting hydrogels. Cross-linking with Ga³⁺ with the carboxylic groups on the polymer chains enhanced the structural stability of the hydrogels and conferred antibacterial activity against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. The engineered bioinks also supported excellent cellular support during bioprinting, as nearly 100% bioprinted cells were viable. When combined with ES, the Ga³⁺-cross-linked CMC/ALG/PEDOT:PSS bioinks significantly enhanced the elongation and proliferation of human skin fibroblasts over 9 days of culture. These results demonstrate the potential of this conductive, antibacterial, and cell-compatible bioink platform, augmented by ES, as a promising strategy to accelerate wound healing and skin tissue regeneration.