Self-Organized Tissue Microvasculature

自组织组织微脉管系统

基本信息

批准号：
7614893
负责人：
David Kevin Wood
金额：
$ 4.72万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7614893
关键词：
Address Adhesions Adhesives Agriculture Albumins Architecture Binding Biological Assay Biotin Blood Vessels Cell Survival Cell physiology Cells Cessation of life Complex Cytochromes Development Devices Drug Metabolic Detoxication Encapsulated Engineering Ethylene Glycols Excision Goals Hepatocyte Hydrogels Image Imagery In Situ In Vitro Laboratories Liquid substance Liver Liver Failure Medical Membrane Metabolic Metabolism Methodology Methods Metric Microfluidics Modeling Monitor Nutrient Organ Organ failure Oxygen Particle Size Pattern Perfusion Pump Research Rivers Sampling Streptavidin Structure Suspension substance Suspensions System Techniques Testing Thick Tissue Engineering Tissue Model Tissues Transplantation United States Urea Velocimetries Waste Products design enzyme activity ethylene glycol improved mortality outcome forecast particle physical model research study self organization success time use trafficking

项目摘要

DESCRIPTION (provided by applicant): Mortality due to organ failure presents a significant medical challenge with liver failure alone responsible for over 35,000 deaths per year in the United States. Currently, the only therapy that offers any significantly improved prognosis is organ replacement, but because the demand for transplantable organs far exceeds supply, only the most severe cases are referred for transplant. While engineered tissues offer the promise to alleviate the suffering imposed by organ failure, they continue to lack key features that would make them a viable treatment option. In particular tissues require a developed vascular network to deliver nutrients and oxygen and to remove metabolic waste products. This is particularly important in highly metabolic and complex tissues like the liver. The problem of vascularizing tissue constructs has been addressed using a variety of approaches, but to date those approaches have seen limited success due primarily to lack of scalability. Self-organization, where basic building blocks are built autonomously into larger structures, has been successfully employed in a variety of engineering applications. We propose that the same physical principles of self-organization that govern the development of river tributaries can be utilized to construct an efficient microvascular network in an adhesive particle suspension. Using cell-laden hydrogel modules as the basic tissue building blocks, we propose to construct a perfusion system in which the macroscopic system parameters can be tuned to create a vascular network that efficiently delivers nutrients to cells throughout the tissue to maintain long-term tissue function and viability. The overall goal of this project is to develop an approach to vascularizing liver tissue in vitro, where the tissue can be designed a priori and built from the ground up using basic tissue building blocks. We hypothesize that physical models of erosion can be applied to suspensions of cell-laden hydrogels and that these models will allow us to optimize the organization of a vascular network that is capable of maintaining cell function and viability. In order to achieve this goal, we propose: (1) to study self-organization in an adhesive suspension of microscale hydrogels under flow and (2) to optimize self-organization of microscale hydrogels for developing a phenotypically functional in vitro liver model. The result will be a fully scalable technique for designing complex tissue architecture from the ground up.

描述（由申请人提供）：器官衰竭导致的死亡是一项重大的医学挑战，在美国，仅肝衰竭就导致每年超过 35,000 人死亡。目前，唯一能显着改善预后的疗法是器官替代，但由于可移植器官的需求远远超过供应，因此只有最严重的病例才会被转诊进行移植。虽然工程组织有望减轻器官衰竭带来的痛苦，但它们仍然缺乏使其成为可行的治疗选择的关键特征。特别是组织需要发达的血管网络来输送营养和氧气并清除代谢废物。这对于肝脏等高度代谢和复杂的组织尤其重要。已经使用多种方法解决了血管化组织构建体的问题，但迄今为止，这些方法取得的成功主要是由于缺乏可扩展性。自组织，即基本构建块自主构建成更大的结构，已成功应用于各种工程应用。我们提出，可以利用控制河流支流发展的相同自组织物理原理在粘合颗粒悬浮液中构建有效的微血管网络。使用充满细胞的水凝胶模块作为基本的组织构建块，我们建议构建一个灌注系统，在该系统中可以调整宏观系统参数以创建一个血管网络，该血管网络可以有效地将营养物质输送到整个组织的细胞，以维持长期的组织功能和生存能力。该项目的总体目标是开发一种体外血管化肝组织的方法，可以先验地设计该组织，并使用基本的组织构建块从头开始构建。我们假设侵蚀的物理模型可以应用于充满细胞的水凝胶悬浮液，并且这些模型将使我们能够优化能够维持细胞功能和活力的血管网络的组织。为了实现这一目标，我们建议：（1）研究流动下微型水凝胶的粘合悬浮液中的自组织；（2）优化微型水凝胶的自组织，以开发表型功能的体外肝脏模型。其结果将是一种完全可扩展的技术，用于从头开始设计复杂的组织结构。