Department of Surgical Oncology, Nuvance Health, Rudy L. Ruggles Biomedical Research Institute, Danbury, Connecticut.
Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Ann Thorac Surg. 2021 Oct;112(4):1089-1094. doi: 10.1016/j.athoracsur.2020.10.021. Epub 2020 Nov 10.
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.
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 surgical patch supported by a 3-dimensional-printed plastic polymer scaffold. Circumferential graft coverage ranged from 50% to 100%, spanning the length of 4 to 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.
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.
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.
使用移植物和生物工程构建物进行气管重建存在争议，这凸显了在应用于人类之前进行动物研究的重要性。小动物模型有助于改进设计，但不能充分模拟与人体解剖结构相关的大小。我们已经进行了广泛的大型动物研究，并在 26 例连续移植中总结了我们的发现。
我们将 26 项大型动物研究汇总在一起，以调查与成功和失败相关的常见因素。通常，工程化气管移植物由脱细胞外基质外科补片组成，由 3D 打印塑料聚合物支架支撑。环周移植物覆盖率从 50%到 100%不等，跨越 4 到 6 个气管环的长度。一些移植物包括嵌入的干细胞。对照移植物是在没有支撑支架的情况下制造的。在死亡时，采集移植物并进行大体和组织学检查。
支撑支架可防止移植物软化和塌陷。具有较小环周覆盖率的移植物中，管腔上皮化最广泛。较小的环周覆盖率也与最长的动物生存时间相关。仅在嵌入干细胞的移植物中观察到软骨生成。100%环周移植物的存活时间最短。肉芽组织是所有移植物设计的一个问题。
大型动物模型可捕获与人体解剖结构相关的挑战和复杂性。肉芽组织的形成仍然是一个挑战，特别是在环周移植物中。需要进行更多的研究来调查肉芽组织的形成，并为其管理提供可操作的见解。
