Bioinspired, injectable, tissue-adhesive and antibacterial hydrogel for multiple tissue regeneration by minimally invasive therapy

Abstract

Hemorrhage and wound infection after soft tissue trauma are the main factors causing casualties in surgical procedures and disasters. Currently available tissue adhesives for hemorrhage and wound infection treatment remain unsatisfactory due to the lack of ideal adhesive hydrogels that can integrate injectability, tunable mechanical strength, matching irregular defect and antibacterial property into one system. Here, inspired by the mussel adhesive protein and the natural extracellular matrix (ECM) composition, we engineered a gelatin-based adhesive hydrogel (Dopamine modified methacrylate gelatin, GMDA) with strong tissue adhesiveness and antibacterial property. This bioinspired injectable hydrogel demonstrated tunable mechanical properties and optimal elasticity due to the double-crosslinked network formed through the horseradish peroxidase (HRP) / hydrogen peroxide (H2O2) and ultraviolet (UV) light crosslinking. In addition, these adhesive hydrogels could withstand up to 250 mmHg blood pressure (significantly higher than normal blood pressure, systolic BP 60–160 mmHg) and showed superior hemostasis capability of uncontrolled bleeding in vivo. Most importantly, the hydrogel exhibited significant antibacterial property because of the released residual H2O2 after hydrogel formation. Further in vivo studies demonstrated that the hydrogel loaded with epidermal growth factor (EGF) could promote efficient skin regeneration with the formation of skin appendages. These findings shed new light on developing a multifunctional bioinspired adhesive hydrogel that could serve as a promising biomaterial for hemostasis and wound infection treatment and other minimally invasive use of biomedical applications.