ADSC-derived exosome-loaded in-situ photocrosslinkable GelMA hydrogels as a treatment strategy for wound healing.

BACKGROUND

Adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) show great promise in wound healing and cutaneous regeneration, but their therapeutic efficacy is limited by rapid systemic clearance, preventing sustained local action at the wound site. Gelatin methacryloyl (GelMA) is a photocrosslinking hydrogel with good biocompatibility and tunable mechanical properties. This study aimed to investigate the effects of GelMA hydrogels loaded with ADSC-Exos (GelMA/ADSC-Exos hydrogels) on the wound healing of full-thickness skin defects.

METHODS

GelMA/ADSC-Exos hydrogels were prepared, and their physical and sustained-release properties were investigated. To assess the effect of GelMA/ADSC-Exos hydrogels on angiogenesis in vitro, the abilities of proliferation, migration, and tube formation of on human umbilical vein endothelial cells (HUVECs) cultured on GelMA/ADSC-Exos hydrogels were assayed. The effect of GelMA/ADSC-Exo hydrogels on wound healing was assessed using a mouse full-thickness excisional skin wound model. To elucidate the underlying mechanism, RNA sequencing was performed, and the effect of GelMA/ADSC-Exo hydrogels on the activity of macrophages was confirmed in vitro.

RESULTS

The composite GelMA/ADSC-Exo hydrogels exhibited desirable mechanical and sustained release properties. They accelerated HUVEC proliferation, adhesion, and tube formation, as well as promoted wound healing in mice with full-thickness skin defects. Further studies showed that these hydrogels promoted macrophage M2 polarization and inhibited the activation of the TLR4/NF-κB pathway.

CONCLUSIONS

The GelMA/ADSC-Exo hydrogels could serve as a promising therapeutic strategy for wound healing.