Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspire...Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspired by sandcastle worm adhesives,we proposed a water-immiscible coacervate(EMNs-gel)with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles.Driven by intestinal peristalsis,the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion,resulting from matrix metalloproteinases(MMPs)-triggered release of Fe3+from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces.Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces,achieving highly effective hemostasis,and displaying an extended residence time(48 h).This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC,showcasing great potential for clinical applications.展开更多
基金Chongqing Postdoctoral International Exchange Training Program(7820100997)Fundamental Research Funds for Central Universities(Nos.SWU-XDPY22010)+2 种基金National College Students Innovation and Entrepreneurship Training Program(202310635114)National Natural Science Foundation of China(No.81703424),Chongqing Graduate Student Research Innovation Project(CYB21121).
文摘Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspired by sandcastle worm adhesives,we proposed a water-immiscible coacervate(EMNs-gel)with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles.Driven by intestinal peristalsis,the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion,resulting from matrix metalloproteinases(MMPs)-triggered release of Fe3+from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces.Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces,achieving highly effective hemostasis,and displaying an extended residence time(48 h).This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC,showcasing great potential for clinical applications.
