Abstract
Short bowel syndrome (SBS) in children, most often caused by necrotizing enterocolitis, volvulus, intestinal atresia, or gastroschisis, results in severe nutrient malabsorption and is associated with high morbidity. Tissue-engineered small intestine (TESI) offers a regenerative alternative to transplantation, circumventing organ scarcity and the need for lifelong immunosuppression. Derived from patient-specific stem cells, TESI can structurally mimic native intestine and integrate functionally, as demonstrated in preclinical rat models showing near-complete weight restoration, prolonged transit time, preserved vitamin B12 levels, and absorptive maturation. TESI generated from human or mouse cells expresses essential enzymes such as sucrase-isomaltase and SGLT-1, supporting glucose absorption, though activity levels remain lower than native tissue. Major challenges include limited tissue yield, potential immune barriers, length constraints, and complex surgical integration. Despite these hurdles, TESI holds promise as a durable, functional cure for pediatric SBS, with successful translation dependent on interdisciplinary collaboration and robust clinical evaluation.