Design and Development of Injectable, Tough and Intrinsically-Adhesive Hydrogels for Biomedical Applications

Despite the development of hydrogels with a wide range of mechanical properties, insufficient adhesion between these materials and biological surfaces limits their use in the biomedical applications. Most recent advancements in highly adhesive hydrogel systems are focused on the preformed hydrogel patches and dry tapes. In the past proposed strategies for highly adhesive hydrogels, the developed materials are not intrinsically adhesive, but adhere to the targeted tissues thanks to specific developments such as chemically modifying the contacting surface. Therefore, hydrogels that exhibit both sufficient intrinsic adhesion to various biological surfaces and proper injectability, has yet to be demonstrated. The need for design, fabrication and characterization of adhesive hydrogel systems with broad physicochemical properties has remained a central challenge in the biomedical field. In the first part, by controlling toughening processes, we design a composite double-network hydrogel with high water content, which creates a dissipative interface and robustly adheres to soft tissues. No tissue surface modification was needed to obtain high adhesion properties of the developed hydrogel. Instead, mechanistic principles were used to control interfacial cracks propagation. The integration of the dissipative polymeric network on the soft tissue surfaces allowed increasing significantly the adhesion strength. Our findings highlight the significant role of controlling hydrogel structure and dissipation processes for toughening the interface. In the second part, we propose a universal framework for the design of injectable hydrogels that are intrinsically adhesive to various tissues. We fabricate a family of original polymeric backbones using a two-step functionalization process in order to make new hydrogels with available adhesive sites and the capability to form hybrid networks, as well as further enhancements through the fiber reinforcement for stronger synergetic effects. To achieve that, our approach (i) provides strong chemical bonds with nucleophiles at interface, immediately upon contact with tissues thanks to the designed available adhesive bonding sites, and (ii) forms a hybrid network by covalent and physical interactions between our engineered chains, so that the interfacial bonds and the hydrogel capability of dissipating energy produce a synergic effect for achieving high adhesion. In addition to high level of adhesion performance, the injectable hydrogel system presents a broad and tunable range of physicochemical properties. This is particularly important for biomedical applications which require superior material properties, such as for cartilage tissue engineering. Fast adhesion formation and one-pot polymerization are achieved while the biosafety concerns, which are crucial for many clinical applications, are satisfied. Finally, with various in vitro, ex vivo, and preliminary in vivo studies, the biocompatibility and potential biomedical