Den Hondt Margot, Vanaudenaerde Bart M, Verbeken Eric K, Vranckx Jan J
Department of Plastic and Reconstructive Surgery, University Hospitals Leuven, Leuven, Belgium.
Department of Chronic Diseases, Metabolism and Ageing, Lung Transplant Unit, Laboratory of Pulmonology, KU Leuven-University of Leuven, Leuven, Belgium.
Interact Cardiovasc Thorac Surg. 2018 May 1;26(5):753-760. doi: 10.1093/icvts/ivx442.
Prerequisites for successful trachea transplantation include the use of a biocompatible construct, submucosal vascularization and an epithelial covering. Implantation of non-epithelialized tracheal scaffolds may lead to stenosis. However, epithelial grafting or seeding can only be attempted onto a well-vascularized submucosal bed. Our aim was to investigate a method to prevent stenosis during prelamination of non-epithelialized, gently decellularized rabbit tracheae and to evaluate whether grafting of revascularized constructs with buccal mucosa is feasible.
Allotracheae underwent two 48-h cycles of detergent-enzymatic decellularization using sodium deoxycholate and DNAse. In the first series, 12 circular scaffolds were implanted bilaterally in lateral thoracic artery flaps (n = 6 rabbits). Right-sided transplants were covered internally with Integra™. In the second series, 10 decellularized tracheae covered with Integra were prelaminated in flaps (n = 10 rabbits). Twenty-one days after implantation, revascularized tracheae were grafted with buccal mucosa. A macroscopic, histological analysis and immunohistochemistry were performed on explants.
In the first series, tracheae without Integra covering developed significantly greater intraluminal (P = 0.032) and subepithelial narrowing (P = 0.0345) compared with tracheae with Integra covering. All tracheae exhibited insufficient submucosal revascularization. In the second series, submucosal revascularization was incomplete in the first 2 constructs, which were implanted circularly. These tracheae only showed marginal buccal graft ingrowth. To accelerate revascularization, the subsequent 8 transplants were opened longitudinally before implantation. Compared to circularly implanted tracheae, submucosal revascularization of these transplants was superior (P = 0.0008). Graft adherence was complete in 6 opened constructs. Mild lymphocytic infiltration within the buccal graft was detected in 5 specimens.
We observed satisfactory host integration of opened tracheae that were temporarily covered with Integra during revascularization and subsequently grafted with buccal mucosa. Integra successfully prevented stenosis during revascularization. This model may provide an example of an immunosuppressive-free approach in the treatment of long-segment tracheal lesions. With the aid of further refinements such as a respiratory epithelial lining, an orthotopically transplantable construct could be created.
成功进行气管移植的先决条件包括使用生物相容性构建体、黏膜下血管化和上皮覆盖。植入未上皮化的气管支架可能会导致狭窄。然而，上皮移植或接种只能在血管化良好的黏膜下层进行。我们的目的是研究一种在未上皮化、轻度去细胞化的兔气管预层压过程中预防狭窄的方法，并评估用颊黏膜移植血管化构建体是否可行。
所有气管均使用脱氧胆酸钠和脱氧核糖核酸酶进行两个48小时的去污剂 - 酶促去细胞化循环。在第一组中，将12个圆形支架双侧植入胸外侧动脉皮瓣（n = 6只兔子）。右侧移植气管内部用Integra™覆盖。在第二组中，将10个用Integra覆盖的去细胞化气管在皮瓣中进行预层压（n = 10只兔子）。植入21天后，用颊黏膜移植血管化的气管。对外植体进行宏观、组织学分析和免疫组织化学检查。
在第一组中，与有Integra覆盖的气管相比，没有Integra覆盖的气管管腔内狭窄（P = 0.032）和上皮下狭窄（P = 0.0345）明显更严重。所有气管均表现出黏膜下血管化不足。在第二组中，最初两个圆形植入的构建体黏膜下血管化不完全，这些气管仅显示颊部移植物边缘向内生长。为了加速血管化，随后的8个移植气管在植入前纵向切开。与圆形植入的气管相比，这些移植气管的黏膜下血管化更好（P = 0.0008）。6个切开的构建体移植物附着完全。在5个标本中检测到颊部移植物内有轻度淋巴细胞浸润。
我们观察到在血管化过程中暂时用Integra覆盖、随后用颊黏膜移植的切开气管与宿主的整合情况令人满意。Integra成功地预防了血管化过程中的狭窄。该模型可能为治疗长段气管病变提供一种无免疫抑制方法的范例。借助进一步改进，如呼吸道上皮内衬，可创建一种可原位移植的构建体。
