Probiotics Behavior‐Inspired Biomimetic Platform for Ulcerative Colitis Prevention and Therapy

Abstract Despite significant advancements in probiotics therapy for ulcerative colitis, its unsatisfactory efficacy and safety concerns impede further clinical applications. Herein, inspired by the natural secretion of outer membrane vesicles (OMVs) and colon colonization behavior of probiotics, a biomimetic probiotics platform (OSM) using bicontinuous single primitive metal–phenolic networks (SP‐MPNs) loaded with OMVs derived from E. coli Nissle 1917 (EcN) is developed. Notably, the ordered mesopores, high specific surface area, and excellent antioxidant properties of SP‐MPNs demonstrate a high loading capacity (≈30%, w / w ) and protective effects for OMVs. Impressively, OSM not only responds to transferrin (Tf) for the slow release of OMVs but also strongly interacts with mucin in the mucus layers, prolonging the retention time of OMVs in the colon (>48 h). Furthermore, OSM exhibits robust antioxidant, anti‐inflammatory, and immunoregulatory activities. Significantly, in comparison with the probiotic EcN, OSM demonstrates superior adhesion properties, higher OMVs release amount, and eliminates the risk of inducing bacteremia. To protect OSM from gastric acid degradation, OSM is encapsulated into ascorbyl palmitate (AP) to form OMVs@SP‐MPNs@AP (OSMA) hydrogel, which demonstrates preventive and therapeutic efficacy in colitis mouse models. In summary, the biomimetic platform provides a promising approach for the prevention and treatment of gastrointestinal disorders.