Optimizing electro-responsive glyoxal-crosslinked alginate hydrogel for the electrochemical detection of NADH and antibacterial activity in smart dressing biointerfaces

Alginate-based hydrogels have attracted considerable attention as scaffolds for wound dressing. In this work, the formulation of an electroactive alginate hydrogel, covalently crosslinked with glyoxal to enhance its stability, was optimized to obtain a multi-tasking scaffold. The optimized hydrogel not only preserves the mechanical softness characteristic of alginate scaffolds but also inhibits bacterial proliferation and functions as an efficient electrochemical sensor capable of detecting bacterial growth in real time. The best performing hydrogel was prepared from a mixture containing 2.6 wt% sodium alginate solution and 20 wt% poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid (relative to sodium alginate). The system is physically crosslinked using 3 wt% CaCl 2 aqueous solution and, subsequently, covalently crosslinked with a 5 wt% glyoxal solution by applying a glyoxalization time of 60 min. The optimized hydrogel enables the quantification of nicotinamide adenine dinucleotide (NADH) over a linear range of up to 10 mM. This sensing capability was successfully applied to the detection of Escherichia coli and Staphylococcus aureus in culture media. Furthermore, the unreacted glyoxal infiltrated within the double-network matrix confers bactericidal properties to the hydrogels without apparently compromising its biocompatibility, as demonstrated using fibroblast cells. Beyond the intrinsic advantages of alginate as biocompatible wound dressing material, optimization of the semi-interpenetrating PEDOT network and the glyoxal crosslinking processes enabled the incorporation of additional functionalities, including NADH sensing for the detection of early bacterial infection and antibacterial activity. Overall, the optimized hydrogels represent promising candidates for use as multifunctional scaffolds in skin wound repair.