Functional integration of an autologous engineered esophagus in a large-animal model. Durkin, N., Hall, G. T., Lutman, R., Scuglia, M., Xenakis, T., Patera, G., Di Biagio, D., Yamada, K., Tullie, L., Scaglioni, D., Shibuya, S., Nikaki, K., Beesley, M. A., Saleh, T., Garrido Flores, M., Borselle, D., Karaluka, V., Hutchinson, J. C., Khalaf, S., Ogunbiyi, O., Wu, L., Huang, X., Song, W., Loukogeorgakis, S., Pellegata, A. F., Mantero, S., Cossu, G., Li, V. S. W., Borrelli, O., Bonfanti, P., Castellano, S., Gerli, M. F. M., McCann, C. J., Eaton, S., Pellegrini, M., & De Coppi, P. Nature Biotechnology, Nature Publishing Group, March, 2026.
Paper doi abstract bibtex 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.
@article{durkin_functional_2026,
title = {Functional integration of an autologous engineered esophagus in a large-animal model},
copyright = {2026 The Author(s)},
issn = {1546-1696},
url = {https://www.nature.com/articles/s41587-026-03043-1},
doi = {10.1038/s41587-026-03043-1},
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.},
language = {en},
urldate = {2026-03-27},
journal = {Nature Biotechnology},
publisher = {Nature Publishing Group},
author = {Durkin, Natalie and Hall, George T. and Lutman, Roberto and Scuglia, Marianna and Xenakis, Theodoros and Patera, Giulia and Di Biagio, Daniele and Yamada, Koji and Tullie, Lucinda and Scaglioni, Dominic and Shibuya, Soichi and Nikaki, Kornilia and Beesley, Max Arran and Saleh, Tarek and Garrido Flores, Matias and Borselle, Dominika and Karaluka, Valerija and Hutchinson, J. Ciaran and Khalaf, Sahira and Ogunbiyi, Olumide and Wu, Lei and Huang, Xia and Song, Wenhui and Loukogeorgakis, Stavros and Pellegata, Alessandro Filippo and Mantero, Sara and Cossu, Giulio and Li, Vivian S. W. and Borrelli, Osvaldo and Bonfanti, Paola and Castellano, Sergi and Gerli, Mattia Francesco Maria and McCann, Conor J. and Eaton, Simon and Pellegrini, Marco and De Coppi, Paolo},
month = mar,
year = {2026},
keywords = {Regeneration, Tissue engineering},
pages = {1--14},
}
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