Engineering a mussel-inspired hemostatic sealant with a strong tissue anchor as a first-aid tissue adhesive

During injury, achieving quick hemostasis, while maintaining adhesive performances on wet tissue and providing appropriate dynamical mechanical properties remain crucial clinical requests for the current tissue adhesives. Here, we design a double-crosslinking tissue adhesive with tunable degradation rate, adhesion strength, mechanical properties, and cell responses, using thiolated gelatin (Gel-SH) or gelatin and tannic acid (TA). We also investigate the role of different concentrations of gelatin (70 and 150 mg/ml), TA (7, 20, and 70 mg/ml), and crosslinkers (sodium periodate (11.3 and 16.8 mg/ml) and Fe3+ ions (1.7 and 4.8 mg/ml)) to provide a balance of covalent and noncovalent interactions leading to establish muscular tissue adhesive strength and superior hemostasis. Our findings reveal that the Gel-SH(gelatin)/TA adhesives have a range of swelling ability (300-700 %), compressive modulus (0.2-1.2 kPa), strength (0.1-0.8 kPa), and toughness (10-15 kJ/m3). In addition, GelSH/TA sample shows rapid self-healing ability and offers robust adhesiveness to wet cow skin and cardiac tissue (50-70 kPa) compared to others mainly owing to the improved cohesive strength originating from the range of chemical interaction within the adhesive network and abundant phenolic hydroxyl groups, surface water removal, and dynamic phenol-quinone balance at the tissue interfaces. Meanwhile, Gel-SH/TA adhesive also exhibits high hemocompatibility and hemostatic properties and appropriate in vitro biocompatibility. Notably, Gel-SH/TA adhesive could support attachment, viability and proliferation, of H9c2 cells. Overall, the multifunctional Gel-SH/TA adhesive hydrogel, owing to the range of molecular interactions opens a new opportunity for quick sealing hemostasis and wound healing and could potentially be harnessed for the development of clinically relevant tissue adhesives.