Self-Organized Tissue Microvasculature

自组织组织微脉管系统

• 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
• 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

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）：由于器官衰竭而导致的死亡率提出了重大的医疗挑战，仅肝脏衰竭造成每年35,000多人死亡。当前，唯一提供任何明显改善预后的疗法是器官的替代品，但是由于对移植器官的需求远远超过了供应，因此只转介了移植最严重的病例。虽然工程组织提供了减轻器官破坏造成的痛苦的承诺，但它们仍然缺乏关键特征，这将使它们成为可行的治疗选择。特别是组织需要开发的血管网络来提供养分和氧气并去除代谢废物。这在高度代谢和复杂的组织（如肝脏）中尤为重要。血管化组织构建体的问题已经使用了多种方法解决，但是迄今为止，这些方法主要是由于缺乏可扩展性而取得的成功有限。在各种工程应用中，已成功地使用了自动建立基本的构建块的自组织。我们建议，可以利用控制河流支流发展的自我组织的物理原理来在粘合粒子悬浮液中构建有效的微血管网络。我们建议使用载有细胞的水凝胶模块作为基本组织构建块，我们建议构建一种灌注系统，可以调节宏观系统参数，以创建一个血管网络，该血管网络有效地为整个组织中的细胞提供营养，以维持长期的组织功能和稳定性。该项目的总体目标是开发一种体外血管肝组织的方法，在该方法中，可以使用基本的组织构建块从头开始设计组织。我们假设可以将侵蚀的物理模型应用于载有细胞水凝胶的悬浮液，这些模型将使我们能够优化能够维持细胞功能和生存能力的血管网络的组织。为了实现这一目标，我们建议：（1）在流动下的显微镜水凝胶的粘附悬浮液中研究自组织，以及（2）优化微观水凝胶的自组织，以开发表型在体外肝模型中。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。