Mussel-Inspired Reusable Tissue Adhesive Hydrogel and its Nanocomposite with Nanoclay for Enhancing Self-Healing and Mechanical Properties

Tissue adhesives are increasingly sought after for their potential to minimize invasiveness, simplify surgical procedures, and reduce operative times; however, conventional polyacrylamide (PAM)-based hydrogels are often hindered by irreversible bonding, which limits their reusability and compromises both mechanical integrity and self-healing ability. Motivated by the natural adhesion mechanisms of mussels, we have developed an innovative tissue adhesive hydrogel by incorporating polydopamine (PDA) and cysteine (Cys) into a PAM matrix via free radical polymerization, with polyethylene glycol diacrylate (PEGDA) serving as an effective cross-linker. In our system, PDA contributes essential catechol groups for strong tissue adhesion, while Cys not only preserves these groups from oxidation but also enhances hydrophilic interactions, resulting in a PDA-Cys-PAM hydrogel with a tensile strength of 23.4-30.7 kPa, a fracture elongation of 628-706%, and an elongation recovery of 48%. Significantly, the seamless integration of nanoclay into the hydrogel network further reinforces its structure and improves energy dissipation, leading to a marked enhancement of the self-healing performance─evidenced by an increase in the elongation recovery rate to 71.9%─without compromising the inherent mechanical properties. Moreover, in vitro assays with NIH3T3 cells demonstrate excellent biocompatibility, underscoring the potential of this synergistic design. Overall, our work not only elucidates the distinct and cooperative roles of PDA, Cys, and nanoclay but also represents a significant advancement in the design of reusable, high-performance tissue adhesives for potential applications in tissue repair and regeneration.