Progress and prospect of studies on tracheal substitute

doi:10.3877/cma.j.issn.2095-8773.2021.03.06

Abstract

Abstract:

To date, tracheal reconstruction after extensive resection remains a major challenge in the field of thoracic surgery. Tracheal replacement with a substitute is needed for reconstruction when the length of tracheal defect is more than 6 cm. Tracheal substitutes include synthetic prosthesis, autologous tissue composite, allograft, xenograft, and tissue-engineered trachea. At present, the ideal trachea substitute is still unclear, but some substitutes have shown good results in animal or clinical applications. This article reviews the achievements and limitations of each tracheal substitute over the past decades. Autologous tissue composite and alloaortic transplantation have shown promises in clinical application. The research on stem cells and tissue-engineered trachea has aroused great interest in recent years, but the poor long-term results of this approach right now highlight that there is still a long way to go in this research field.

Key words: Tracheal substitute, Synthetic prosthesis, Autologous tissue composite, Allogeneic graft, Xenograft, Tissue-engineering

Ke Xu, Haitang Yang, Chenxi Zhong, Heng Zhao, Feng Yao. Progress and prospect of studies on tracheal substitute[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2021, 08(03): 164-173.

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Figures/Tables 2

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类型	文献	年份	例数	并发症	随访时间	内容
自体组织气管	Spaggiari等^[24]	2005	1	ARDS，气管狭窄	24个月	尝试胸壁皮瓣替代气管，获得良好短期疗效
	Yu等^[31]	2006	1	无	6个月	使用前臂筋膜瓣联合人工刚性支撑物能够获得良好短期效果，且不需要支架植入
	Fabre等^[33]	2013	12	肺部感染	4~101个月	使用前臂游离筋膜瓣构建导管，并横向插入肋骨软骨加强，避免了支架相关的并发症
	Zhang等^[32]	2015	5	咯血	14~84个月	使用带弹性金属支架的自体肺组织瓣重建气道是一种可行的选择
同种异体气管	Rose等^[35]	1979	1	无	9周	第一次成功将该方法应用于临床，获得良好的短期疗效，但缺乏长期疗效及随访信息。
	Zhao等^[37]	1999	2	无	60个月	摸索出合适的气管低温保存方法
	Xu等^[39]	2014	3	无	6个月	采用大网膜包裹异体气管进行分期移植，能为气管建立良好血供
	Delaere等^[40]	2010	1	无	12个月	在二阶段移植技术的基础上尝试撤退免疫抑制剂方案
	Delaere等^[25]	2012	5	黏膜坏死，气管环软化	6个月	在软骨间韧带做部分切口，并用受体黏膜替换部分供体黏膜有利于促进免疫抑制剂撤退，为气管替代提供更详尽的临床经验
同种异体主动脉	Hoffman等^[43]	2001	1	无	3 d	主动脉被用作临时的气管替代物修复缺损
	Azorin等^[44]	2006	1	双侧肺炎	6个月	自体主动脉首次被作为替代物对气管进行长期的替代
	Wurtz等^[47]	2010	6	吻合口开裂胸骨开裂真菌感染	26~42个月	使用同种异体主动脉结合内支撑支架和外支撑肌瓣进行气管替代，血管化良好并有局部呼吸道上皮衬里，但所有患者均不能脱离支架
	Martinod等^[49]	2017	2	急性喉水肿支架细菌感染，支架肉芽肿	55~67个月	开发了使用低温保存（-80 ℃）的同种异体主动脉移植物作为生物基质的体内生物工程气管替代物的技术，发现主动脉内有软骨再生
	Martinod等^[50]	2018	13	喉水肿，急性肺水肿，ARDS，心房颤动	18~85个月	证明使用带支架的主动脉基质进行复杂气管和支气管重建的可行性，患者能够获得长期生存
组织工程气管	Elliott等^[6]	2012	1	气道塌陷	24个月	以干细胞为基础的组织工程化移植物具有良好的上皮化、血管化潜能。但目前尚不清楚植入的工程气道是否具有生长能力，以及移植后的长期结果
	Hamilton等^[64]	2015	1	肉芽组织形成远端气管狭窄	48个月	尽管需要多个支架及多次支气管镜检查及干预，但脱细胞组织工程气管在儿童体内具有长期存活能力
	Elliott等^[65]	2017	1	急性气道压迫胸腔出血可能	15 d	总结出接种自体细胞的脱细胞气管支架移植的标准操作程序，并建议至少在移植后的最初几个月内使用气管支架
	Tan等^[75]	2017	1	无	4个月	通过体外灌注培养系统促进体内的组织工程气管原位再生，随访证实替代物完全血管化、再上皮化，且在接受放化疗后无相关并发症发生
	Xu等^[76]	2020	3	胃潴留肺炎	18~25个月	将体外灌注的体内生物反应器技术应用于侵犯隆凸的长段气管病变，再生组织血管化良好，无渗漏

类型	文献	年份	例数	并发症	随访时间	内容
自体组织气管	Spaggiari等^[24]	2005	1	ARDS，气管狭窄	24个月	尝试胸壁皮瓣替代气管，获得良好短期疗效
	Yu等^[31]	2006	1	无	6个月	使用前臂筋膜瓣联合人工刚性支撑物能够获得良好短期效果，且不需要支架植入
	Fabre等^[33]	2013	12	肺部感染	4~101个月	使用前臂游离筋膜瓣构建导管，并横向插入肋骨软骨加强，避免了支架相关的并发症
	Zhang等^[32]	2015	5	咯血	14~84个月	使用带弹性金属支架的自体肺组织瓣重建气道是一种可行的选择
同种异体气管	Rose等^[35]	1979	1	无	9周	第一次成功将该方法应用于临床，获得良好的短期疗效，但缺乏长期疗效及随访信息。
	Zhao等^[37]	1999	2	无	60个月	摸索出合适的气管低温保存方法
	Xu等^[39]	2014	3	无	6个月	采用大网膜包裹异体气管进行分期移植，能为气管建立良好血供
	Delaere等^[40]	2010	1	无	12个月	在二阶段移植技术的基础上尝试撤退免疫抑制剂方案
	Delaere等^[25]	2012	5	黏膜坏死，气管环软化	6个月	在软骨间韧带做部分切口，并用受体黏膜替换部分供体黏膜有利于促进免疫抑制剂撤退，为气管替代提供更详尽的临床经验
同种异体主动脉	Hoffman等^[43]	2001	1	无	3 d	主动脉被用作临时的气管替代物修复缺损
	Azorin等^[44]	2006	1	双侧肺炎	6个月	自体主动脉首次被作为替代物对气管进行长期的替代
	Wurtz等^[47]	2010	6	吻合口开裂胸骨开裂真菌感染	26~42个月	使用同种异体主动脉结合内支撑支架和外支撑肌瓣进行气管替代，血管化良好并有局部呼吸道上皮衬里，但所有患者均不能脱离支架
	Martinod等^[49]	2017	2	急性喉水肿支架细菌感染，支架肉芽肿	55~67个月	开发了使用低温保存（-80 ℃）的同种异体主动脉移植物作为生物基质的体内生物工程气管替代物的技术，发现主动脉内有软骨再生
	Martinod等^[50]	2018	13	喉水肿，急性肺水肿，ARDS，心房颤动	18~85个月	证明使用带支架的主动脉基质进行复杂气管和支气管重建的可行性，患者能够获得长期生存
组织工程气管	Elliott等^[6]	2012	1	气道塌陷	24个月	以干细胞为基础的组织工程化移植物具有良好的上皮化、血管化潜能。但目前尚不清楚植入的工程气道是否具有生长能力，以及移植后的长期结果
	Hamilton等^[64]	2015	1	肉芽组织形成远端气管狭窄	48个月	尽管需要多个支架及多次支气管镜检查及干预，但脱细胞组织工程气管在儿童体内具有长期存活能力
	Elliott等^[65]	2017	1	急性气道压迫胸腔出血可能	15 d	总结出接种自体细胞的脱细胞气管支架移植的标准操作程序，并建议至少在移植后的最初几个月内使用气管支架
	Tan等^[75]	2017	1	无	4个月	通过体外灌注培养系统促进体内的组织工程气管原位再生，随访证实替代物完全血管化、再上皮化，且在接受放化疗后无相关并发症发生
	Xu等^[76]	2020	3	胃潴留肺炎	18~25个月	将体外灌注的体内生物反应器技术应用于侵犯隆凸的长段气管病变，再生组织血管化良好，无渗漏

方法	原理	优点	缺点
自体组织气管	以带血管蒂的管状自体组织为主体，附加支撑物作为支撑	血管化良好，组织相容性好	有狭窄坍塌风险，缺乏纤毛清除黏液的能力
同种异体气管	供体气管在异位再血管化数周后进行原位移植	保留天然气管的结构与功能，再血管化程度良好	需要供体，再血管化时间较长，需要使用免疫抑制剂
同种异体主动脉	以新鲜的或经过冷冻保存的同种异体主动脉作为管道替代气管，通常需要支架作为支撑	可通过组织库永久储存，不需要使用免疫抑制剂	缺乏纤毛清除黏液的能力，血供不充分
组织工程气管	在可生物降解支架或脱细胞供体气管中植入受体干细胞，通过干细胞分化和募集周围细胞来填充移植物	具有生长潜能，不需要使用免疫抑制剂	技术要求高，再血管化难度大

方法	原理	优点	缺点
自体组织气管	以带血管蒂的管状自体组织为主体，附加支撑物作为支撑	血管化良好，组织相容性好	有狭窄坍塌风险，缺乏纤毛清除黏液的能力
同种异体气管	供体气管在异位再血管化数周后进行原位移植	保留天然气管的结构与功能，再血管化程度良好	需要供体，再血管化时间较长，需要使用免疫抑制剂
同种异体主动脉	以新鲜的或经过冷冻保存的同种异体主动脉作为管道替代气管，通常需要支架作为支撑	可通过组织库永久储存，不需要使用免疫抑制剂	缺乏纤毛清除黏液的能力，血供不充分
组织工程气管	在可生物降解支架或脱细胞供体气管中植入受体干细胞，通过干细胞分化和募集周围细胞来填充移植物	具有生长潜能，不需要使用免疫抑制剂	技术要求高，再血管化难度大

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[2]	Deli Tan, Shirong Zhang, Longwen Xu. Advances and challenges of patient-derived tumor xenograft model in hepatocellular carcinoma [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(03): 251-257.
[3]	Qiqi Jiang, Yikuan Feng, Kai Zhang, Qian Li, Wansheng Ji. Role of Δ133p53 in the growth of human gastric cancer cell MKN-45 transplanted tumor [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2021, 11(05): 215-219.
[4]	Qiaoli Guo, Hui Hu. Application of patient-derived xenograft model in study of triple-negative breast cancer [J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(10): 790-793.

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