Regenerative strategies for esophageal and tracheal reconstruction

Children with congenital foregut malformations including tracheal pathology or long-gap esophageal atresia have limited treatment options. Severe malformations have suboptimal replacement options for both congenital and acquired anomalies despite maximal surgical intervention. Tissue engineering offers a potential solution to address this unmet need. For esophageal reconstruction, the combination of decellularized extracellular matrix scaffolds, myogenic progenitor cells, and bioreactor pre-conditioning has shown the most promising preclinical results. For tracheal replacement, there have been initial reports in pediatric patients, but no strategy has yet demonstrated consistent preclinical success, and the optimal approach remains to be defined. The two fields are at markedly different stages of translational readiness. Tracheal tissue engineering has not yet achieved consistent safety or durability in orthotopic large-animal models, and clinical use has been confined to a small number of compassionate-use cases with mixed outcomes partly related to inconsistent use of scaffold materials and cell replacement strategies. Esophageal reconstruction is closer to clinical translation, with a clinical trial of segmental replacement in adults underway and full-thickness circumferential replacement with evidence of secondary peristalsis demonstrated in a growing large-animal model. Pediatric patients impose unique constraints for tissue engineering but also offer advantages, including enhanced tissue remodeling capacity. Bridging the gap between current preclinical progress and safe clinical application will demand robust animal model validation, transparent documentation of setbacks, and sustained interdisciplinary engagement. This review summarizes current strategies for tracheal and esophageal reconstruction using tissue-engineered approaches, evaluating preclinical and clinical evidence across scaffold design, cell sourcing, and vascularization.