Schiff-base bioelectric and bioactive hydrogel dressing based on chitosan, alginate, and poly(N-isopropylacrylamide)...

The development of advanced hydrogel dressings that provide a moist, extracellular matrix (ECM) -like environment while also regulating bioelectric cues and the inflammatory-angiogenic balance is crucial for the effective repair of full-thickness skin defects. This study reports the fabrication of a multifunctional hydrogel dressing (QOP) by integrating glycidyl trimethyl ammonium chloride-modified chitosan (QCS), aldehyde alginate (OSA), and poly(N-isopropylacrylamide) (pNiPAM), together with conductive poly(3,4-ethylenedioxythiophene)@polydopamine (PEDOT@PDA) nanoparticles, where PDA imparts adhesive and antioxidant properties. The therapeutic potential of the QOP hydrogel was further enhanced by incorporating baicalein, chosen for its anti-inflammatory and pro-angiogenic properties. As a result, the fabricated QOP hydrogels exhibited a suite of favorable properties, including porosity, swelling capacity (>380 %), storage modulus (6-8.5 kPa), rapid self-healing (within 5 min), conductivity and biocompatibility. Furthermore, in a full-thickness skin defect mouse model, the baicalein-loaded QOP hydrogel (B-QOP hydrogel) demonstrated superior wound closure rates and enhanced tissue regeneration, including an increase in epidermal length, dermal thickness, and blood vessel formation compared to the hydrogel without baicalein. Mechanistic investigation revealed that the B-QOP hydrogel downregulated the inflammatory factor TNF-α while upregulating the angiogenic factor VEGF. In conclusion, the baicalein-incorporated conductive QOP hydrogel, with its multifaceted functionality, demonstrates potential for the repair of full-thickness skin defects.