(540b) Stretchable, Tough, Bioadhesive Hydrogels Based on Naturally-Derived Biopolymers for Regenerative Engineering of Soft Tissues

It has been extremely challenging to engineer highly dynamic tissues, such as lungs and arteries. The existing biomaterials based on naturally-derived polymers suffer from the lack of resilience or robustness needed for undergoing severe cyclic forces. On the other hand, the synthetic counterparts have shown inferior cytocompatibility and tissue regeneration properties in vivo. This makes it crucial to develop tough and resilient hydrogels, which are based on natural polymers, so that they can provide a cell-friendly environment for tissue regeneration in vivo. Gelatin methacryloyl (GelMA) is an inexpensive, naturally-derived, and photo-crosslinkable biopolymer that has demonstrated a high capacity for tissue engineering applications due to its biocompatibility and tunable physical properties. However, GelMA is a mechanically weak hydrogel with a failure stain as low as 30%. Here, we overcome this major shortcoming of GelMA by hybridizing it with a mussel-based biopolymer, dopamine methacryloyl (DMA), which can impart an ion-mediated reversible crosslinking to dissipate energy under strain. This resulted in the formation a highly stretchable and tough double-network hydrogel with tunable mechanical properties comparable to those for native lungs and arteries. The synthesized hydrogel was also highly tissue adhesive, which provided opportunities for the sutureless tissue grafting and sealing. Our ex vivo study demonstrated that the toughness of a damaged porcine artery anastomosed with the GelMA/DMA hydrogel was 10 times higher than that for pure GelMA (10 vs 100 Jm^-3). Also, our in vivo model indicated that the hybrid gel was highly biocompatible with excellent tissue regeneration properties that maintained its structural integrity over the course of several weeks. This study provided a novel class of hydrogels with a unique combination of mechanical robustness, tissue regenerativity, and bioadhesivity. This, combined with extremely low manufacturing costs, will make the engineered hydrogels clinically translational for a variety of applications in soft tissue engineering and regenerative medicine.