1 Division of Pediatric Surgery, Loma Linda Children's Hospital, Loma Linda, California, USA.
2 Center for Regenerative Medicine, Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Otolaryngol Head Neck Surg. 2019 Sep;161(3):458-467. doi: 10.1177/0194599819844754. Epub 2019 Apr 30.
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.
Large animal model.
Pediatric academic research institute.
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.
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.
In our ovine model, clinically applied synthetic tissue-engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.
接受组织工程气管移植物的患者预后较差，最终导致死亡或需要移植物取出。我们通过羊原位气管置换模型评估了在人体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。
大动物模型。
儿科学术研究机构。
用人造聚对苯二甲酸乙二醇酯和聚氨酯的电纺混合物制造支架，并使用聚碳酸酯环增强，然后用自体骨髓来源的单核细胞接种。将动物进行常规支气管镜和荧光检查评估。对移植物狭窄进行内镜扩张和支架置入，以管理长达 4 个月的时间点。对移植物和相邻的天然气道进行切片，用组织学和免疫组织化学进行评估。
所有动物均有移植物狭窄的迹象。5 只动物中有 3 只（60%）指定进行长期监测，直到 4 个月时间点。移植物扩张和支架置入解决了呼吸症状并延长了生存时间。尸检显示有感染和移植物包裹的证据。吻合处可见有肉芽组织和新生血管的迹象，但从未观察到上皮化。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陷和支架分层。
在我们的羊模型中，临床应用的合成组织工程气管显示出感染、炎症和机械故障，缺乏上皮化和新生血管形成。
