L-Proline loaded ferulic acid-alginate dialdehyde-gelatin hydrogel for wound healing applications

Abstract

Chronic wounds are characterized by persistent oxidative stress and impaired extracellular matrix (ECM) regeneration, necessitating biomaterials capable of simultaneously modulating the wound microenvironment and supporting tissue remodeling. In this study, an alginate dialdehyde gelatin hydrogel co-incorporating ferulic acid and L-proline (ADAGFAP) was developed in addition to ferulic acid alone hydrogel (ADAGFA) via dynamic Schiff-base crosslinking to provide antioxidant protection alongside matrix-forming support. Physicochemical characterization confirmed stable network formation, nanostructured surface morphology, pH-responsive release behavior, and controlled degradation. In vitro evaluation using HaCaT keratinocytes demonstrated excellent cytocompatibility, enhanced cell migration, reduced intracellular reactive oxygen species, and increased collagen deposition compared to control hydrogels. While ferulic acid loaded hydrogels exhibited pronounced migratory responses, the dual ADAGFAP system provided a reduced antioxidant potential than ADAGFA possibly due to the interactions between ferulic acid and L-Proline within the hydrogel matrix. These findings highlight the potential of careful tailoring of multifunctional alginate gelatin hydrogels as promising platforms for wound healing applications.