Requirements for successful trachea transplantation; a study in the rabbit model

Background: Although creating a tracheal tube de novo might appear straightforward, the first clinical applications have shown that reconstruction of long-segment tracheal defects remains challenging. In this study, we aimed to refine the baseline requirements of successful trachea transplantation by means of three proof-of-concept models in the rabbit. Methods: In each model, one characteristic of a perfect tracheal transplant was eliminated. The first model was developed to map out the immunological response of vascularized allogenic trachea, transplanted without immunosuppression (n = 6). The second model studied the need for wrapping the transplant with a highly-vascularized flap, and the source of angiogenesis after autologous trachea-transplantation (n = 18). In the third model, we examined the importance of an inner epithelial covering (n = 12). All models were compared to a control group of heterotopically transplanted vascularized autologous tracheae (n = 6). Results: Embedded in an avascular matrix, allogenic chondrocytes were protected from an overt immune response. Orthotopic transplantation without additional external vascular wrap was successful in a well-vascularized environment. Nonetheless, an external vascular source was essential to maintain viability of the construct. Epithelial covering was necessary to prevent secondary healing. Epithelial migration from the anastomoses or graft was not sufficient to cover long-segment defects. Conclusions: These experiments provided ample evidence of the importance of baseline requirements when designing a tracheal-transplant study. This study confirmed that different tracheal cell-types possess different immunological sensitivities. External revascularization, preferably in a two-stage procedure, and fast reepithelialization were both paramount to successful transplantation. Financial disclosure: The authors of this manuscript have no conflicts to disclose as described by Plastic and Reconstructive Surgery. None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgements: This work was supported by the predoctoral fellowship of the Research Foundation Flanders (FWO; 11I0413N) of Margot Den Hondt. Corresponding Author: Margot Den Hondt, margot.denhondt@uzleuven.be, +32 494 18 64 83 ©2018American Society of Plastic Surgeons

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