Hybrid Biological Hydrogel Provides Favorable Bioenergetic, Adhesive, and Antioxidative Effects on Wound Healing

Wound healing is a dynamic and complex process that demands substantial energy expenditure and a biomimetic microenvironment. Developing a simple and effective biological hydrogel to enhance mitochondrial energy metabolism could effectively promote wound healing. To this end, we developed a hybrid biological hydrogel based on <i>Escherichia coli</i> lipoate protein ligase A (LplA), which combines its catalytic and self-assembling properties to promote wound healing. In murine fibroblast L929 cell models, LplA significantly enhances cellular activity and intracellular metabolism, promoting cell proliferation and energy supply. However, cells aggregated into spherical clusters on the pure LplA hydrogel. To address this issue, we integrated glutaraldehyde (GA) as a cross-linker into the LplA hydrogel. The GA-LplA hydrogel enhances cell adhesion and proliferation and, unexpectedly, exhibits higher catalytic activity compared with the pure LplA hydrogel. Furthermore, LplA was observed to decompose H₂O₂, and the GA-LplA hybrid hydrogel significantly reduced reactive oxygen species (ROS) production. The promise of this hybrid hydrogel is successfully demonstrated in a male mice full-thickness skin defect model with accelerated re-epithelialization and cell proliferation while reducing inflammation.