1 Department of Urology, The James Buchanan Brady Urological Institute , The Johns Hopkins School of Medicine, Baltimore, Maryland.
2 Department of Chemical and Biomolecular Engineering, Johns Hopkins University , Baltimore, Maryland.
Tissue Eng Part A. 2018 Oct;24(19-20):1456-1467. doi: 10.1089/ten.TEA.2017.0436. Epub 2018 Jun 4.
Decellularized tissues have been increasingly popular for constructing scaffolds for tissue engineering applications due to their beneficial biological compositions and mechanical properties. It is therefore natural to consider decellularized trachea for construction of tissue-engineered trachea, as well as other tubular organs. A Neo-Urinary Conduit (NUC) is such a tubular organ that works as a passage for urine removal in bladder cancer patients who need a urinary diversion after their diseased bladder is removed. In this study, we report our findings on the feasibility of using a decellularized trachea for NUC applications. As a NUC scaffold, decellularized trachea provides benefits of having not only naturally occurring biological components but also having sufficient mechanical properties and structural integrity. We, therefore, decellularized rabbit trachea, evaluated its mechanical performance, and investigated its ability to support in vitro growth of human smooth muscle cells (hSMCs) and human urothelial cells (hUCs). The decellularized trachea had appropriate biomechanical properties with ultimate tensile strength of ∼0.34 MPa in longitudinal direction and ∼1.0 MPa in circumferential direction and resisted a radial burst pressure of >155 mm Hg. Cell morphology study by scanning electron microscopy further showed that hUCs grown on decellularized trachea adopted a typical flatten and interconnected network structure in the lumen of the scaffold, while they formed a round spherical shape and did not spread on the outer surfaces. SMCs, on the other hand, spread well throughout the scaffold. The gene expression analysis by real time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence studies further confirmed scaffold's ability to support long-term growth of hSMCs. Since uroepithelium has been shown to regenerate itself over time in vivo, these findings suggest that it is possible to construct a NUC from decellularized trachea without any preseeding of UCs. In future, we plan to translate decellularized trachea in a preclinical animal model and evaluate its biological performance.
去细胞组织因其有益的生物成分和机械性能而越来越受到用于组织工程应用的支架构建的青睐。因此，考虑使用去细胞气管构建组织工程气管以及其他管状器官是很自然的。Neo-Urinary Conduit (NUC) 就是这样一种管状器官，它作为膀胱癌患者在切除患病膀胱后进行尿液引流的通道。在这项研究中，我们报告了使用去细胞气管进行 NUC 应用的可行性研究结果。作为 NUC 支架，去细胞气管不仅提供了具有天然存在的生物成分的优势，而且还具有足够的机械性能和结构完整性。因此，我们对兔气管进行了去细胞处理，评估了其机械性能，并研究了其支持人平滑肌细胞（hSMCs）和人尿路上皮细胞（hUCs）体外生长的能力。去细胞气管具有适当的生物力学特性，纵向的拉伸强度约为 0.34 MPa，环向的拉伸强度约为 1.0 MPa，抵抗径向爆裂压力>155 mmHg。扫描电子显微镜下的细胞形态学研究进一步表明，在支架管腔中生长的 hUC 呈典型的扁平且相互连接的网络结构，而在支架外表面上则呈圆形且未展开。另一方面，SMC 很好地在整个支架上扩散。实时定量聚合酶链反应 (RT-qPCR) 的基因表达分析和免疫荧光研究进一步证实了支架支持 hSMC 长期生长的能力。由于尿路上皮在体内会随着时间的推移而自我再生，这些发现表明，可以使用去细胞气管构建 NUC，而无需预先接种 UC。在未来，我们计划在临床前动物模型中转化去细胞气管，并评估其生物学性能。
