Factors Influencing Poor Outcomes in Synthetic Tissue-Engineered Tracheal Replacement
Factors Influencing Poor Outcomes in Synthetic Tissue-Engineered Tracheal Replacement
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DOI：
10.1177/0194599819844754
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发表时间：
2019-09-01
影响因子：
3.4
通讯作者：
Chiang, Tendy
中科院分区：
文献类型：
--
作者：
Pepper, Victoria;Best, Cameron A.;Chiang, Tendy
目的：接受组织工程气管移植的人类经历了不良的结局，最终导致死亡或需要移植物再移植。我们评估了人类原位气管置换绵羊模型中使用的合成支架的性能，应用标准的术后监测和干预措施来确定导致床边并发症的因素。研究设计大型动物模型。单位：儿科学术研究所。受试者和方法人体支架用聚对苯二甲酸乙二醇酯和聚碳酸酯环增强的聚氨酯的静电纺丝共混物制造。他们与自体骨髓来源的单核细胞接种并植入绵羊体内。通过常规支气管镜检查和荧光透视对动物进行评价。进行内镜扩张和支架植入术，以管理移植物狭窄长达4个月的时间点。将移植物和邻近的天然气道切片并进行组织学和免疫组织化学评价。结果所有动物均出现移植血管狭窄。指定用于长期监测的5只动物中有3只（60%）存活至4个月时间点。移植物扩张和支架置入解决了呼吸道症状，延长了生存期。尸检证实存在感染和移植物包囊的证据。肉芽组织与新生血管的迹象，看到在新生血管，但从未观察到上皮形成。在所有时间点均观察到天然气道上皮的急性和慢性炎症。支架的结构变化包括后壁内折和支架分层。结论在我们的绵羊模型中，临床应用的合成组织工程气管表现出感染、炎症和机械故障，缺乏上皮形成和新血管形成。
Objectives Humans receiving tissue-engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside. Study Design Large animal model. Setting Pediatric academic research institute. Subjects and Methods Human scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow-derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4-month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry. Results All animals had signs of graft stenosis. Three of 5 animals (60%) designated for long-term surveillance survived until the 4-month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination. Conclusions In our ovine model, clinically applied synthetic tissue-engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.