In the present study, a hybrid microsphere/hydrogel system, consisting of polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel incorporating PCL microspheres is introduced as a skin scaffold to accelerate wound healing. The hydrogel substrate was developed using the freeze-thawing method, and the proportion of the involved polymers in its structure was optimized based on the in-vitro assessments. The bFGF-encapsulated PCL microspheres were also fabricated utilizing the double-emulsion solvent evaporation technique. The achieved freeze-dried hybrid system was then characterized by in-vitro and in-vivo experiments. The results obtained from the optimization of the hydrogel showed that increasing the concentration of SA resulted in a more porous structure, and higher swelling ability, elasticity and degradation rate, but decreased the maximum strength and elongation at break. The embedding of PCL microspheres into the optimized hydrogel structure provided sustained and burst-free release kinetics of bFGF. Besides, the addition of drug-loaded microspheres led to no significant change in the degradation mechanism of the hydrogel substrate; however, it reduced its mechanical strength. Furthermore, the MTT assay represented no cytotoxic effect for the hybrid system. The in-vivo studies on a burn-wound rat model, including the evaluation of the wound closure mechanism, and histological analyses indicated that the fabricated scaffold efficiently contributed to promoting cell-induced tissue regeneration and burn-wound healing.
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