Bioreactor for Nondestructive Study of Disease in Tissue

描述(由申请人提供)： 为了在体外研究疾病的发病机制，迫切需要先进的体内模拟系统(IVSS，例如生物反应器)来支持各种组织类型的体外维持。本提案的目标是开发一种更接近生理环境的生物反应器系统，同时利用非破坏性生物医学成像技术来研究工程组织或天然组织的结构和功能。这项工作的成果将是一个仪器系统，用于研究环境因素对组织发育和组织疾病状态的影响。该系统的新颖性在于无损评估能力与先进的可控闭环机械、生化和流体控制系统相结合，以更好地模拟生理条件。参与该提案的团队在生物反应器系统设计方面的最新进展有助于将动态多维机械刺激与精确和准确地控制生物化学和流体环境相结合，用于韧带组织工程。将这一专业技术与非侵入性成像技术(显微镜、核磁共振)相结合，为现场确定许多重要的生物工程参数提供了独特的机会。第一阶段(R21)的目标是演示一种新的反应堆容器设计的原则证明，该设计支持韧带组织的生长和发展(作为基于我们初步研究的示范模型)，同时连接非破坏性成像系统(例如，显微镜和MRI)。第二阶段(R33)将寻求扩大反应堆容器设计，以支持更多盘状组织类型的生长和研究，如骨栓。同时，将设计和开发模块化的反应堆容器墨盒和先进的IVSS闭环机械、生化和流体控制系统，同时继续确保反应堆容器能够与选定的成像系统对接。来自塔夫茨大学、哈佛大学、麻省理工学院和马萨诸塞州总医院的跨学科研究团队结合了他们的专业知识来解决这个问题的复杂性，其中许多人在组织工程和生物反应器设计方面有着长期的合作。

DESCRIPTION (provided by applicant): There is a strong scientific and clinical need for advanced in vivo simulation systems (IVSS, e.g., bioreactors) that support the maintenance of various tissue types in vitro in order to study disease pathogenesis in vitro, The goal of this proposal is to develop a bioreactor system that better approximates physiological environments while utilizing advances in non-destructive biomedical imaging techniques to study the structure and function of engineered or native tissues. The outcome of this work will be an instrumentation system to study the effects of environmental factors on tissue development and tissue disease states. The novelty of the system is in the non-destructive assessment capabilities combined with advanced controllable close-loop mechanical, biochemical and fluidic control systems to better mimic physiological conditions. Recent advances by the team involved in this proposal in bioreactor systems design have contributed to the combination of dynamic multi-dimensional mechanical stimulation with precise and accurate control over the biochemical and fluidic environments for ligament tissue engineering. Combining this expertise with noninvasive imaging techniques (microscopy, NMR) offers a unique opportunity to determine many important bioengineering parameters in situ. The objective of Phase I (R21) is to demonstrate proof-of-principle for a new reactor vessel design that supports the growth and development of ligament tissue (as an exemplary model based on our preliminary studies) while interfacing non-destructive imaging systems (e.g., microscopy and MRI). Phase II (R33) will seek to expand the reactor vessel design to support the growth and study of additional disc-like tissue types such as bone plugs. In parallel, modular reactor vessel cartridges and advanced IVSS close-loop mechanical, biochemical and fluidic control systems will be designed and developed while continually ensuring the reactor vessel is able to interface the selected imaging systems. An interdisciplinary team of investigators from Tufts University, Harvard University, MIT and Massachusetts General Hospital have combined their expertise to address the complexities of this topic, many of whom have longstanding collaborations in tissue engineering and bioreactor designs.