Tissue-Engineered Neo-Urinary Conduit from Decellularized Trachea

• Published in: Tissue engineering. Part A 2018-10, Vol.24 (19-20), p.1456-1467
• Main Authors: Singh, Anirudha, Lee, David, Jeong, Harrison, Yu, Christine, Li, Jiuru, Fang, Chen Hao, Sabnekar, Praveena, Liu, Xiaopu, Yoshida, Takahiro, Sopko, Nikolai, Bivalacqua, Trinity J.
• Format: Article
• Language: English
• Subjects: Bladder cancer; Cancer; Cytology; Experiments; Gene expression; Immunofluorescence; Mechanical properties; Original Articles; Polymerase chain reaction; Scanning electron microscopy; Smooth muscle; Tissue engineering; Trachea; Urine
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2017.0436

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.