Hydrogels, Cornea, Tissue adhesive, Mesenchymal stem cell exosomes, Wound healing, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5

Abstract Hydrogels have shown great potential and value in wound healing. In this study, we construct a mesenchymal stem cell exosomes (MSC-Exos) laden natural biopolymer-based hydrogel with transparent, self-healing, injectable, and tissue adhesive properties to promote corneal regeneration. This hydrogel is synthesized by combining aldehyde-modified oxidized guar gum (OGG) and carboxymethyl chitosan (CMCS) through the dynamic, reversible Schiff base bonds, which endow it with outstanding shear-thinning and self-healing properties, facilitating easy injection through a needle. The physicochemical properties, such as porosity, mechanical strength, and light transmittance, could be precisely tunable by adjusting OGG concentrations. The resultant hydrogel achieves robust tissue adhesion at physiological temperatures due to Schiff base interactions. Besides, the Exos can be uptaken by the corneal epithelial cells and subsequently promote the migration of the cells. We have proven that the MSC-Exos-loaded hydrogel adheres firmly to the defected cornea and significantly improves wound repair by enhancing collagen deposition and reducing inflammation in a rabbit cornea defect model. These results indicated that this multifunctional hydrogel holds immense scientific promise and offers a wide range of clinical applications.