Sustained delivery of extracellular vesicles using UiO-66-NH2 crosslinked hydrogel for accelerating chronic diabetic wound-healing

Abstract

Many patients with diabetes are suffering with chronic wounds due to their slow and disorganized healing process, which even lead to serious consequences such as amputation. Nowadays, extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) offer a potential strategy for chronic wound healing, whereas the rapid diffusion and degradation of MSC-EVs hampers the efficacy of wound repair. Herein, we proposed a novel MOF-based hydrogel by cross-linking hyaluronic acid (HA) with UiO-66-NH2 (U6N). The HA-U6N hydrogel could be prepared rapidly with stable character, while the EVs affinity property of U6N was maintained well. This hydrogel allowed us enriching EVs conveniently and rapidly from cell supernatant. The U6N-based hyaluronic acid hydrogel with enriched EVs (HA-U6N-EVs) could markedly accelerate diabetic wound healing efficacy in rats attributing to the sustained release of EVs. Besides, we further showed the miRNAs in MSC-EVs involving in wound healing remained high abundance over 10 days, also demonstrating the superb sustained EVs delivery of HA-U6N hydrogels.

Keywords

• Mesenchymal stromal cells
• Extracellular vesicles
• Metal–organic frameworks
• Hydrogel
• Sustained release
• Chronic wound healing