Controlled Release of Epidermal Growth Factor from Furfuryl-Gelatin Hydrogel Using in Situ Visible Light-Induced Crosslinking and Its Effects on Fibroblasts Proliferation and Migration

Abstract

Hydrogels are widely used in tissue engineering as materials that regulate cell proliferation, migration, and differentiation. They also act as promising biomaterials that can provide a variety of stimuli by influencing the surrounding microenvironment, which can be achieved by modulating their mechanical properties, thereby aiding soluble factor delivery. Here, we developed a gelatin-based injectable hydrogel that has controllable mechanical properties and demonstrates sustained drug release without the need for invasive surgery. Gelatin was modified with furfuryl groups, and riboflavin phosphate was used as a photoinitiator to crosslink the hydrogel using visible light. A hydrogel–with a storage modulus in the range of 0.2–15 kPa was formed by maintaining the concentration of furfuryl-gelatin within 10–30% w/v. Consequently, their mechanical properties can be tailored for their applications. The furfuryl-gelatin hydrogel was loaded with maleimide-modified epidermal growth factor (EGF) as a model drug to achieve a controlled-release system. The sustained release of maleimide-EGF due to gelatin hydrogel matrix degradation was observed. Cell proliferation and scratch assays were performed to verify its effect on fibroblasts. When EGF was physically entrapped in the hydrogel matrix, the released EGF considerably affected cell proliferation and scratch closure of fibroblasts at the beginning of the culture. By contrast, maleimide-EGF was released sustainably and steadily and affected cell proliferation and scratch closure after the initial stage. We demonstrated that the release of soluble factors could be controlled by modulating the mechanical properties. Thus, the injectable hydrogel formed by in situ visible light-induced crosslinking could be a promising biomaterial for tissue engineering and biomedical therapeutics.