Bio-inspired swellable hydrogel-forming double-layered adhesive microneedle protein patch for regenerative internal/external surgical closure.

Significant tissue damage, scarring, and an intense inflammatory response remain the greatest concerns for conventional wound closure options, including sutures and staples. In particular, wound closure in internal organs poses major clinical challenges due to air/fluid leakage, local ischemia, and subsequent impairment of healing. Herein, to overcome these limitations, inspired by endoparasites that swell their proboscis to anchor to host's intestines, we developed a hydrogel-forming double-layered adhesive microneedle (MN) patch consisting of a swellable mussel adhesive protein (MAP)-based shell and a non-swellable silk fibroin (SF)-based core. By possessing tissue insertion capability (7-times greater than the force for porcine skin penetration), MAP-derived surface adhesion, and selective swelling-mediated physical entanglement, our hydrogel-forming adhesive MN patch achieved ex vivo superior wound sealing capacity against luminal leaks (139.7 ± 14.1 mmHg), which was comparable to suture (151.0 ± 23.3 mmHg), as well as in vivo excellent performance for wet and/or dynamic external and internal tissues. Collectively, our bioinspired adhesive MN patch can be successfully used in diverse practical applications ranging from vascular and gastrointestinal wound healing to transdermal delivery for pro-regenerative or anti-inflammatory agents to target tissues.