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

用于肺和气管脱细胞和再细胞化评估和系统优化的先进生物反应器

• 批准号: 523396-2018
• 负责人: Amon, Cristina
• 金额: $ 9.33万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=643872
• 关键词: Advanced; Bioreactors; Evaluation; Systematic; Optimization

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.

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的挽救生命的选择。理想情况下，我们需要获得现成的替代移植物，减少对捐赠器官的依赖，等待时间和死亡风险。在肺中，器官再生是通过使用部分合成或天然支架的生物混合装置来实现的。该方法是利用先进的生物反应器在优化的生理条件下操作，以 ** 重新填充新细胞，其中驻留细胞已被移除的支架，并用于受损组织的功能性替代。虽然再生全肺移植是一个遥远的目标，但我们利用更简单的气管系统，我们拥有广泛的专业知识，同时解决关键问题，为未来全肺移植的临床应用奠定基础。在资助期结束时，我们预计将开始临床 ** 翻译功能性气管生物移植物，用于解决小气道和较大的气管 ** 缺陷，分别。开发的优化的气管生物反应器可以通过向现有的肺生物技术公司授权或通过专注于增强的器官特异性生物反应器的公司创建企业来产生商业产品。此外，使用血管（和气道）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计算机实验程序探索靶向细胞递送的策略。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，有可能挽救生命，并大大改善患有终末期肺病的加拿大人的生活质量。