Functional integration of an autologous engineered esophagus in a large-animal model
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Natalie Durkin George T Hall Roberto Lutman Marianna Scuglia Theodoros Xenakis Giulia Patera Daniele Di Biagio Koji Yamada Lucinda Tullie Dominic Scaglioni Soichi Shibuya Kornilia Nikaki Max Arran Beesley Tarek Saleh Matias Garrido Flores Dominika Borselle Valerija Karaluka J Ciaran Hutchinson Sahira Khalaf Olumide Ogunbiyi Lei Wu Xia Huang Wenhui Song Stavros Loukogeorgakis Alessandro Filippo Pellegata Sara Mantero Giulio Cossu Vivian Li Osvaldo Borrelli Paola Bonfanti Sergi Castellano Mattia Francesco Maria Gerli Conor J McCann Simon Eaton Marco Pellegrini Paolo De Coppi
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Abstract
Tissue engineering of the esophagus has been limited by stent dependance and poor muscle regeneration. Here we report an integrated strategy to engineer a 2.5-cm esophageal segment by microinjecting autologous pericyte-like myogenic precursors and fibroblasts in a decellularized porcine scaffold to repair circumferential defects in 10-kg minipigs (n = 8), modeling pediatric use. Bioreactor maturation induced a proangiogenic phenotype, with in vivo support from biodegradable intraluminal stents and a vascularizing pleural wrap. This coordinated approach yielded safe and effective esophageal conduits; oral feeding supported normal growth, morbidity resembled that of clinical esophageal replacement and was endoscopically manageable, and 63% (5/8) survived to the 6-month endpoint. Comprehensive multimodal analyses demonstrated progressive recapitulation of native architecture, with increasing neuromuscular regeneration and vascularization, correlating with functional recovery, absence of symptomatic stricture and the presence of secondary peristalsis by 6 months. These results demonstrate that the combination of complementary regenerative, conditioning and surgical strategies enables a functionally integrated, contractile esophageal graft with ongoing structural maturation without immunosuppression.
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Nature Biotechnology
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10.1038/s41587-026-03043-1
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41862601
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41862601
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