Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.

Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as ßCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) side-chains from ß-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, ßCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, ßCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, ßCP hydrogel enables simultaneous loading and on-demand release of diverse categories of drugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery.

Submucosal injection material has shown protective effect against gastrointestinal injury during endoscopic surgery in clinic. However, the protective ability of existing submucosal injection material is strictly limited by their difficult injectability and short barrier time. Herein, we report a shear-thinning gellan gum hydrogel that simultaneously has easy injectability and long-lasting barrier function, together with good hemostatic property and biocompatibility. Shear-thinning property endows our gellan gum hydrogel with excellent endoscopic injection performance, and the injection pressure of our gellan gum hydrogel is much lower than that of the small molecule solution (50 wt% dextrose) when injected through the endoscopic needle. More importantly, our gellan gum hydrogel shows much stronger barrier retention ability than normal saline and sodium hyaluronate solution in the ex vivo and in vivo models. Furthermore, our epinephrine-containing gellan gum hydrogel has a satisfactory hemostatic effect in the mucosal lesion resection model of pig. These results indicate an appealing application prospect for gellan gum hydrogel utilizing as a submucosal injection material in endoscopic surgery.