Bowel Regeneration: Bench to Bedside

Pediatric intestinal failure resulting from short bowel syndrome remains a significant source of morbidity and mortality despite advances in parenteral nutrition and multidisciplinary intestinal rehabilitation. While native intestinal adaptation provides a foundation for recovery in many patients, those with the most severe forms of short bowel syndrome face limited therapeutic options, including lifelong parenteral nutrition dependence, surgical lengthening procedures, and intestinal transplantation-each associated with substantial complications. The field of bowel regeneration has expanded dramatically over the past two decades, drawing on advances in stem cell biology, biomaterials science, mechanotransduction, and bioengineering. This review examines the current landscape of bowel regeneration strategies through a conceptual framework that progresses from native adaptation, through cellular and biological therapies, to structural and mechanical approaches, and ultimately to tissue engineering as the integration of cellular and structural strategies. Emerging technologies including gene editing for regional reprogramming of intestinal identity, three-dimensional bioprinting, and advanced organoid-scaffold systems are discussed as they relate to the future of clinical translation. Although significant hurdles remain-particularly in vascularization, innervation, and scaling of engineered constructs-the trajectory of the field suggests that regenerative approaches may fundamentally alter the management of pediatric intestinal failure within the coming decades.