Background: Necrotizing enterocolitis (NEC) is a life-threatening condition characterized by necrosis of the gastrointestinal tract caused by hypoperfusion and hypoxia-induced inflammation. Surgical treatment often requires resection, with high morbidity and mortality. Intestinal tissue engineering using absorbable biomaterials represents a potential alternative. Small intestinal submucosa (SIS) is a biodegradable extracellular matrix (ECM) scaffold that may facilitate regeneration of the native tissue. Objectives: The aim of our study is to investigate the regenerative potential of SIS in a rat model with multiple gastrointestinal defects. Methods: In rats, after a midline laparotomy, an approximately 1 cm full-thickness incision was performed on the anterior gastric wall, on the antimesenteric side of the small and large intestine, each covered with an SIS patch. After three weeks, the graft sites and adjacent fragments were harvested and fixed in 10% neutral buffered formalin. Cross-sections of the grafted area were processed and stained with hematoxylin and eosin for histologic analysis. Results: Among the fifteen Wistar rats used in the study, the survival rate was 80% (12/15). Macroscopic examination of the abdominal cavity after the second surgery showed no complications. Adhesions were present in 92% (11/12). Histological examination demonstrated complete mucosal coverage in all stomach samples, nine of the small intestine, and ten of the large intestine. Mild fibrosis with minimal inflammatory infiltrates predominated. Ulceration with granulation tissue replacement was observed in three small intestine samples. Foreign body reactions were restricted to suture sites. Conclusions: In this multifocal injury model, SIS integrated effectively and supported early regenerative healing across gastric, small-intestinal, and colonic sites at 3 weeks. These data support further studies with longer follow-up, quantitative histology and functional assessment, and evaluation in neonatal-relevant large animal models to determine translational potential for NEC surgery.
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