Skin-inspired injectable adhesive gelatin/HA biocomposite hydrogel for hemostasis and full-thickness dermal wound healing

An insufficient adhesion to wet surfaces and biased functions for therapeutic efficacy are limitations to the application of gelatin and hyaluronic acid. Herein, we developed a simple double-injection approach to prepare a skin-inspired gelatin/HA-based injectable remoistenable adhesive hydrogel (HI/DA-Gel) through a simultaneous crosslinking and bio-compositing strategy of genipin incorporated with dopamine (DA) grafted gelatin and N-hydroxy succinimide (NHS) merged with hyaluronic acid. The integrative crosslinking and bio-compositing strategy led to the formation of a HI/DA-Gel with a highly skin-bionic interconnected internal double network 3D-structure with elevated surface wettability, thermal-stablity, adhesive and mechanical properties as expected. In vitro/in vivo biostudies showed that HI/DA-Gel enhanced collagen deposition, hemostatic effects and upregulated the production of CD31, showing an effective hemostasis and full-thickness dermal wound healing strategy. This work proposes a novel facile double-injection approach for the design of gelatin/ hyaluronic acid multi-functional injectable bio-composite hydrogels for integrated therapeutic effects.