Synthesis of Agarose-Based Multistimuli-Responsive Hydrogel Dressing for Accelerated Wound Healing.

Stimuli-responsive hydrogels have drawn increasing research interest in regenerative medicine due to their tunable molecular structures and functional properties for both providing a suitable microenvironment for wound healing and to serve as a sustainable therapeutic. Hence, we developed a stimuli-responsive drug-loaded hydrogel wound dressing for sustained, controlled release of the drug and accelerating wound healing. Hydrogel dressings with stimuli-responsive properties were prepared using carboxymethyl agarose (CMA) with various degrees of substitution and calcium ion crosslinking, followed by the loading of recombinant human epidermal growth factor (Rh-EGF) on the CMA hydrogel. Experimental results indicated that these hydrogel composites showed pH and temperature stimuli-responsive behaviors and released the encapsulated drug sustainedly in various release media. Moreover, the hydrogel dressings exhibited a porous network structure, stable physical properties, and excellent biocompatibility. The investigation in vivo showed that the Rh-EGF-loaded CMA hydrogel dressing significantly enhanced wound healing and reduced inflammatory responses by upregulating the transforming growth factor-beta, vascular endothelial growth factor, and cluster of differentiation 31 (CD31). These results confirm that Rh-EGF-loaded CMA hydrogel dressings possess potential application in accelerating wound healing and tissue regeneration.