Injectable Self‐Healing Natural Biopolymer‐Based Hydrogel Adhesive with Thermoresponsive Reversible Adhesion for Minimally Invasive Surgery

Abstract Biocompatible hydrogel adhesives with multifunctional properties, including injectability, fast self‐healing, and suitable on‐demand detachment, are highly desired for minimally invasive procedures, but such materials are still lacking. Herein, an injectable self‐healing biocompatible hydrogel adhesive with thermoresponsive reversible adhesion based on two extracellular matrix‐derived biopolymers, gelatin and chondroitin sulfate, is developed to be used as a surgical adhesive for sealing or reconnecting ruptured tissues. The resulting hydrogels present good self‐healing and can be conveniently injected through needles. The strong tissue adhesion at physiological temperatures originates from the Schiff base and hydrogen bonding interactions between the hydrogel and tissue that can be weakened at low temperatures, thereby easily detaching the hydrogel from the tissue in the gelation state. In vivo and ex vivo rat model show that the adhesives can effectively seal bleeding wounds and fluid leakages in the absence of sutures or staples. Specifically, a proof of concept experiment in a damaged rat liver model demonstrates the ability of the adhesives to act as a suitable laparoscopic sealant for laparoscopic surgery. Overall, the adhesive has several advantages, including low cost and ease of production and application that make it an exceptional multifunctional tissue adhesive/sealant, effective in minimally invasive surgical applications.