Injectable gelatin-poly(ethylene glycol) adhesive hydrogels with highly hemostatic and wound healing capabilities

Abstract

Although numerous poly(ethylene glycol) (PEG)-based bioadhesives have been developed and commercialized for various biomedical applications, their biocompatibility and bioactivity performances are generally lacking. In addition, the development of adhesive hydrogels with rapid gelation and high tissue adhesion are desirable to promote the surgical procedures and enhance patient compliance. To overcome these problems, we designed a series of chemically crosslinked gelatin-PEG adhesive hydrogels (GP) through the enzymatic crosslinking reaction of horseradish peroxidase (HRP). The resultant GP hydrogels were rapidly formed in situ within seconds to minutes after injection, and their mechanical as well as adhesive properties were adjustable in a wide range by changing the molecular weight and content of PEG. Notably, the hybrid hydrogels composed of 20 kDa PEG with ratio of 2.5/7.5 gelatin/PEG (wt/wt) showed 11 times greater tissue adhesiveness than commercially available fibrin glues. From in vitro cell studies, the hybrid adhesive hydrogels are nontoxic and improve the cell proliferation. Importantly, the hydrogels exhibited excellent hemostatic capability and accelerated the wound healing in vivo, compared to fibrin glue. These injectable GP hydrogels effectively improved the tissue adhesiveness and bioactivity of PEG-based adhesives, and hold great potential for hemostatic and wound healing treatments.