HydroGEV: Extracellular Vesicle-Laden Hydrogel for Wound Healing Applications

Chronic wounds contribute a substantial social and economic burden on the healthcare system. The global cost of wound treatment was about $19.8 Billion USD in 2019. Healing of chronic wounds takes typically more than 3 months. Current treatments are ineffective and do not always promote wound closure, which requires the activation of multiple cell types. Extracellular vesicles (EVs) contain multiple biomolecules that influence surrounding cells and thus have large capacity to promote tissue repair. To harness the chemoattractant properties of EVs, we developed an extracellular vesicle-laden hydrogel (HydroGEV) with optimized stiffness to promote functional tissue repair, since both mechanical and biological factors influence cell growth and subsequent tissue repair. EVs were isolated and purified from placental stem cells, characterized and incorporated into a gelatin-based hydrogel (GHPA) with different relative stiff-nesses (low, medium and high) determined by crosslinking density. The EVs were found to increase the migration capability of cells in a migration assay, confirming their strong chemoattractant properties and supporting their application for cell recruitment in wound healing. When incorporated into GHPA hydrogels, the EVs effectively improved cell attachment regardless of the stiffness of the hydrogels. Importantly, we demonstrated that by optimizing hydrogel stiffness it was possible to achieve higher cell proliferation and more phenotypic morphology. These promising results support the potential of HydroGEV as a better therapeutic option for patients with acute or chronic wounds.