Successes and failures in tracheal bioengineering: Lessons learned

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Article

Abstract

Background: Controversy in tracheal reconstruction using grafts and bioengineered constructs highlights the importance of animal studies before human application. Small animal models help to refine designs, but do not adequately model sizes relevant to human anatomy. We have conducted extensive large animal studies and summarize our findings in 26 consecutive transplants.
Methods: We pooled 26 large animal studies together to investigate common elements related to successes and failures. In general, the engineered tracheal graft consisted of a decellularized extracellular matrix (ECM) surgical patch supported by a 3D printed plastic polymer scaffold. Circumferential graft coverage ranged from 50% to 100%, spanning the length of 4-6 tracheal rings. Some grafts included embedded stem cells. Control grafts were fabricated without the support scaffold. At death, grafts were harvested and examined grossly and through histology.
Results: The support scaffold prevented graft malacia and collapse. Luminal epithelialization was most extensive in grafts with smaller circumferential coverage. Smaller circumferential coverage was also associated with longest animal survival. Chondrogenesis was only observed in grafts with embedded stem cells. Survival time was shortest in 100% circumferential grafts. Granulation tissue was an issue for all graft designs.
Conclusions: Large animal models capture challenges and complexities relevant to human anatomy. Development of granulation tissue remains a challenge, especially in circumferential grafts. Significant additional research is needed to investigate granulation tissue formation and to provide actionable insight into its management.

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Publication (Name of Journal)

The Annals of Thoracic Surgery

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