Hyaluronic acid hydrogel for controlled release of heterobifunctional photocleavable linker-modified epidermal growth factor in wound healing

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications.