In-situ formed elastin-based hydrogels enhance wound healing via promoting innate immune cells recruitment and angiogenesis

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

Automated summary

This study developed bioactive elastin-based hydrogels that can recruit and modulate innate immune cells, accelerate angiogenesis, and improve wound regeneration. The hydrogels showed tunable mechanical properties and were able to mimic the dermal microenvironment. In vitro co-culture experiments demonstrated that the derived conditioned medium from the hydrogels promoted the expression of M1 and M2 markers in macrophages and induced superior tube formation in endothelial cells. In a mouse wound model, the hydrogels attracted neutrophils and M2 macrophages to the wound, leading to enhanced angiogenesis, collagen deposition, and dermal regeneration.