Advanced Bioreactors for Evaluation and Systematic Optimization of Decellularization and Recellularization of the Lung and Trachea

影响呼吸道的疾病是一个重要的临床问题，对于大多数患有终末期疾病的患者来说，肺和/或气管移植已成为唯一**挽救生命的选择。理想情况下，我们需要获得现成的替代移植物，以减少对捐献器官的依赖、等待时间和死亡风险。在肺部，器官再生是通过使用部分合成或天然支架的生物杂交设备来实现的。方法**是利用在优化的生理条件下运行的先进生物反应器，**重新填充新的细胞，其中驻留的细胞已经被移除，并使用**对受损组织进行功能性替换。虽然再生完整肺的移植是一个遥远的目标，但我们开发了更简单的气管系统，我们拥有**广泛的专业知识，同时解决了将为未来全肺移植的临床**应用奠定基础的关键问题。在资助期结束时，我们预计将开始临床**转换用于分别解决小气道和较大气管**缺陷的功能性气管生物移植物。开发的优化气管生物反应器可以通过授权给现有的肺部生物技术公司或通过公司**创建专注于增强型器官特定生物反应器的公司**来产生商业**产品。此外，使用血管(和呼吸道)网络的计算机化几何模型**开发流体流动的计算模型**将允许电子实验计划探索**靶向细胞输送的**策略。这里开发的模型有可能在肺组织工程中产生重大影响，并可应用于专注于其他**器官的研究小组。这项工作的完成将启动一项治疗战略，有可能**拯救生命，并极大地改善患有终末期肺部疾病的加拿大人的生活质量。

Diseases affecting the airways are an important clinical problem and for the majority of**patients with end-stage disease, transplantation of lung and/or trachea has become the only**life-saving option. Ideally we need access to off-the-shelf replacement grafts reducing the**dependency on donor organs, wait-time and risk of death. In the lung, organ regeneration is**achieved by using biohybrid devices with partially synthetic or natural scaffolds. The approach**is to utilize advanced bioreactors operating under optimized physiological conditions to**repopulate with new cells, scaffolds in which the resident cells have been removed, and use**for functional replacement of damaged tissue. While transplantation of regenerated whole**lungs is a far-off goal, we exploit the simpler system of the trachea with which we have**extensive expertise while addressing key issues that will set the foundation for future clinical**application of whole lung grafts. At the end of the funding period, we expect to begin clinical**translation of a functional tracheal biograft used to address small airway and larger tracheal**defects, respectively. The optimized tracheal bioreactors developed can result in commercial**products via licensing to already existing lung biotech companies or through company**creation ventures with focus on enhanced organ-specific bioreactors. In addition, the**development of a computational model of fluid flow using a computerized geometrical models**of vascular (and airway) networks will allow in silico experimental programs to explore**strategies for targeted cell delivery. Models developed here have the potential for significant**impact in lung tissue engineering, and can be applied to research groups focused on other**organs. Completion of this work will set in motion a therapeutic strategy with the potential to**save lives and vastly improve the quality of life of Canadians suffering from end-stage lung**disease.