Bioresponsive microneedle stent provides anastomosis and postoperative adjuvant therapy in preclinical resectable intestinal diseases

Successful treatment of resectable intestinal diseases hinges on advanced intestinal anastomosis techniques and effective postoperative management. However, current postoperative adjuvant therapy remains limited to systemic administration of medications after conventional hand-sewn anastomosis, frequently leading to associated complications and potential recurrence. Here, we introduce a microneedle anastomotic stent (MAS) for postoperative intestinal healing and localized drug delivery in resectable intestinal diseases. This MAS integrates a biodegradable polyglycolic acid stent with a stimulus-responsive polyprodrug microneedle patch. This design provides robust mechanical properties, effective prevention of anastomotic leakage, and on-demand drug release at the anastomotic site. After intestinal resection, the MAS is implanted at the anastomotic site, where the microneedles penetrate the mucosal layer and release the anti-inflammatory drug in response to hyperinflammatory conditions, thereby attenuating local inflammation and facilitating anastomotic healing. In vitro assays verified the minimal cytotoxicity and good biocompatibility of the MAS and its degradation products. The efficacy of the MAS in tissue penetration and stimulus-responsive drug release was demonstrated using ex vivo patient samples. The in vivo therapeutic benefit and mechanism of the MAS were validated in the murine radiation colitis model, and its feasibility and safety were further confirmed in the minipig model of ischemic inflammatory injury. The MAS also exhibited versatility as a delivery platform for diverse therapeutics, suggesting potential applications in complex intestinal diseases. Compared with conventional methods, in preclinical studies, the MAS offered a sutureless approach for intestinal anastomosis and postoperative adjuvant therapy, holding potential for treating various resectable intestinal diseases.