An artificial liquid-liquid phase separation-driven silk fibroin-based adhesive for rapid hemostasis and wound sealing.

The powerful adhesion systems of marine organisms have inspired the development of artificial protein-based bioadhesives. However, achieving robust wet adhesion using artificial bioadhesives remains technically challenging because the key element of liquid-liquid phase separation (LLPS)-driven complex coacervation in natural adhesion systems is often ignored. In this study, mimicking the complex coacervation phenomenon of marine organisms, an artificial protein-based adhesive hydrogel (SFG hydrogel) was developed by adopting the LLPS-mediated coacervation of the natural protein silk fibroin (SF) and the anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SF/SDBS complex coacervate enabled precise spatial positioning and easy self-adjustable deposition on irregular substrate surfaces, allowing for tight contact. Spontaneous liquid-to-solid maturation promoted the phase transition of the SF/SDBS complex coacervate to form the SFG hydrogel in situ, enhancing its bulk cohesiveness and interfacial adhesion. The formed SFG hydrogel exhibited intrinsic advantages as a new type of artificial protein-based adhesive, including good biocompatibility, robust wet adhesion, rapid blood-clotting capacity, and easy operation. In vitro and in vivo experiments demonstrated that the SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, thus advancing its clinical applications. STATEMENT OF SIGNIFICANCE: Marine mussels utilize the liquid-liquid phase separation (LLPS) strategy to induce the supramolecular assembly of mussel foot proteins, which plays a critical role in strong underwater adhesion of mussel foot proteins. Herein, an artificial protein-based adhesive hydrogel (named SFG hydrogel) was reported by adopting the LLPS-mediated coacervation of natural protein silk fibroin (SF) and anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SFG hydrogel enabled the precise spatial positioning and easy self-adjustable deposition on substrate surfaces with irregularities, allowing tight interfacial adhesion and cohesiveness. The SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, exhibiting intrinsic advantages as a new type of artificial protein-based bioadhesives.

Multifunctional Dual Cross-Linked Bioadhesive Patch with Low Immunogenic Response and Wet Tissues Adhesion.

The development of bioadhesives is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, that is, strong adhesion, water resistance, and high biocompatibility. Here, a biocompatible and biodegradable protein-based bioadhesive patch (PBP) with high adhesion strength and low immunogenic response is reported. PBP exists as a strong adhesion for biological surfaces, which is higher than some conventional bioadhesives (i.e., polyethylene glycol and fibrin). Robust adhesion and strength are realized through the removal of interfacial water and fast formation of multiple supramolecular interactions induced by metal ions. The PBP's high biocompatibility is evaluated and immunogenic response in vitro and in vivo is neglected. The strong adhesion on soft biological tissues qualifies the PBP as biomedical glue outperforming some commercial products for applications in hemostasis performance, accelerated wound healing, and sealing of defected organs, anticipating to be useful as a tissue adhesive and sealant.