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Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds

Moser, PT; Gerli, M; Diercks, GR; Evangelista-Leite, D; Charest, JM; Gershlak, JR; Ren, X; ... Ott, HC; + view all (2020) Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds. Tissue Engineering Part A , 26 (9-10) pp. 545-555. 10.1089/ten.TEA.2019.0128. Green open access

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Abstract

Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bio-engineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we generated laryngeal scaffolds with preserved glycosaminoglycan content and biomechanical properties by detergent perfusion-decellularization over nine days. We proofed biocompatibility by absence of a CD3 lymphocyte response to subcutaneously implanted scaffolds in immune-competent rats. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated re-endothelialized arterial and venous vascular beds. Under the same culture medium condition, we bio-engineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in heterotopic transplantations in immuno-deficient mice. The model supported the formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing, complex, multicellular, ready-to-transplant tissue grafts.

Type: Article
Title: Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/ten.TEA.2019.0128
Publisher version: https://doi.org/10.1089/ten.TEA.2019.0128
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10085679
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