3D Microvascular Networks in Hydrogels Fabricated with Sacrificial Structures

用牺牲结构制造的水凝胶中的 3D 微血管网络

• 批准号: 8164062
• 负责人: Leon Marcel Bellan
• 金额: $ 8.74万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8164062
• 关键词: Academia; Affect; Astronomy; Biocompatible Materials; Biomedical Engineering; Blood Vessels; Blood capillaries; Caring; Cell Density; Cell Line; Cells; Coculture Techniques; Complex; Country; Development; Devices; Diffusion; Drug Delivery Systems; Ecology; Educational process of instructing; Endothelial Cells; Engineering; Ensure; Environment; Eudragit; Faculty; Gel; Gelatin; Goals; Hospitals; Hydrogels; Learning; Libraries; Liquid substance; Mentors; Microfluidics; Nutrient; Organic solvent product; Patients; Phase; Physics; Physiological; Polymers; Positioning Attribute; Process; Production; Research; Research Institute; Research Personnel; Scheme; Schools; Science; Solubility; Stem cells; Structure; Students; Surface; System; Techniques; Technology; Temperature; Thick; Time; Tissue Engineering; Tissues; Universities; Vascular System; Work; Writing; aqueous; base; capillary; cell type; clinically significant; experience; high school; interest; melting; methylmethacrylate-methacrylic acid copolymer; outreach program; pressure; prevent; programs; scaffold; skills; tissue support frame; volunteer

DESCRIPTION (provided by applicant): Candidate I have been performing research in academic labs since high school, and have for a long time known that I want to pursue a carer in academia as a profesor. I have research experience in fields ranging from astronomy to environmental science to applied physics, and am now focusing on exploiting a fabrication technology I developed at the end of graduate school to solve a major problem in the field of tisue engineering. My interests lie in the development of smart materials and biomaterials, and I consider natural tissue in itself to be an ultimate form of smart material, able to interact with its environment in extraordinarily complex ways. I am not only interested in the research aspects of academia, but also care a great deal about teaching and mentoring young students; I have mentored several undergraduates and a masters student, helped direct student research in a class as an undergraduate, and have volunteered for a wide variety of outreach programs. During my postdoctoral experience in the Langer Lab, I will learn the skills necessary to become an independent investigator (such as proposal writing, mentoring, dealing with academic bureaucracies, etc.), and plan to apply for a faculty position within a few years. I also plan to learn more about the field of biomedical engineering, and the unique issues that are associated with it Environment The work discussed in the mentored phase of this proposal will be performed in the Langer Lab at MIT. The Langer lab is widely known as one of the leading research groups in a wide range of fields, including drug delivery, tissue engineering, smart materials, and biomedical device engineering. The Langer Lab is located at MIT, one of the leading research institutes in the country, with strong connections to several local hospitals. The independent phase of this proposal will be performed at a university with a strong biomedical engineering and materials science research program. Research (Please note highlighted sections contain proprietary information) The work discussed in this proposal focuses on developing 3D microfluidic networks inside hydrogels to act as artificial vascular systems in engineered tissue. Such vascular networks will be required for any engineered tissue of significant (and clinically useful) thickness, as diffusion limits the ability of nutrients and gasses to pass to and from cells embedded deep within a scaffold. The fabrication technique is based on the use of sacrificial melt-spun microfiber networks made from materials with pH-dependant solubility. The structures produced in many ways mimic natural capillary networks, and are produced with a rapid, simple, inexpensive, and scalable process. The aims in this proposal discuss techniques to produce the desired structures, as well as techniques for seeding cells on the channel walls (as an endothelial lining) as well as in the hydrogel material (as functional cells in a 3D matrix). In all cases, the cells will be maintained by media flow through the 3D channel system. In the mentored phase of this work, the scaffold fabrication technique will be developed, and seeding of cells on the channel walls will be demonstrated. This phase will also contain the initial work necessary to optimize the sacrificing technique to allow cells to be placed in the hydrogel, though it is possible this aim may continue through to the independent phase. The independent phase will demonstrate fabrication of 3D networks in a cell-laden hydrogel (first without, and then with, cells lining the channel walls as well). The independent phase will then develop co- culture systems in these vascularized hydrogels, and may also investigate the use of the 3D channel network to deliver factors to affect stem cells embedded within the hydrogel. PUBLIC HEALTH RELEVANCE: The progress of modern tissue engineering depends on the ability to form 3D vascular networks that are able to provide nutrients to cells inside of artificial tissue constructs. Using a new technique based on sacrificial melt-spun microfiber structures, we will be able to produce these networks rapidly and inexpensively, thereby rendering the resulting vascularized artificial tissue constructs accessible to the patient. The constructs will be made of hydrogels such as gelatin, which are very similar to natural tissue, and will contain cells that will allow the construct to function like native tissue.

描述（由申请人提供）： 候选人 我从高中起就一直在学术实验室进行研究，并且很长时间以来都知道我想在学术界担任教授。我在天文学、环境科学和应用物理学等领域拥有研究经验，现在专注于利用我在研究生毕业时开发的制造技术来解决组织工程领域的一个主要问题。我的兴趣在于智能材料和生物材料的开发，我认为自然组织本身就是智能材料的终极形式，能够以极其复杂的方式与其环境相互作用。我不仅对学术界的研究方面感兴趣，而且非常关心教学和指导年轻学生；我指导过几名本科生和一名硕士生，在本科生期间帮助指导学生在课堂上的研究，并自愿参加了各种外展项目。在兰格实验室的博士后经历中，我将学习成为一名独立研究者所需的技能（例如提案撰写、指导、处理学术官僚机构等），并计划在几年内申请教职职位。我还计划更多地了解生物医学工程领域，以及与其相关的独特问题。 环境 本提案指导阶段讨论的工作将在麻省理工学院的兰格实验室进行。兰格实验室被广泛认为是药物输送、组织工程、智能材料和生物医学设备工程等广泛领域的领先研究小组之一。兰格实验室位于美国领先的研究机构之一麻省理工学院，与当地多家医院有着密切的联系。该提案的独立阶段将在一所拥有强大生物医学工程和材料科学研究项目的大学进行。研究（请注意突出显示的部分包含专有信息）本提案中讨论的工作重点是开发水凝胶内的 3D 微流体网络，以充当工程组织中的人工血管系统。任何具有显着厚度（且临床上有用）的工程组织都需要这种血管网络，因为扩散限制了营养物质和气体传入和传出嵌入支架深处的细胞的能力。该制造技术基于使用牺牲性熔纺微纤维网络，该网络由具有 pH 依赖性溶解度的材料制成。 这些结构以多种方式模仿天然毛细管网络，并通过快速、简单、廉价且可扩展的工艺生产。该提案的目的是讨论产生所需结构的技术，以及在通道壁（作为内皮衬里）以及水凝胶材料（作为 3D 矩阵中的功能细胞）中接种细胞的技术。在所有情况下，细胞将由流经 3D 通道系统的媒体流维持。在这项工作的指导阶段，将开发支架制造技术，并将演示细胞在通道壁上的接种。该阶段还将包含优化牺牲技术所需的初始工作，以允许将细胞放置在水凝胶中，尽管这一目标可能会持续到独立阶段。独立阶段将演示在充满细胞的水凝胶中构建 3D 网络（首先没有细胞，然后也有细胞排列在通道壁上）。然后，独立阶段将在这些血管化水凝胶中开发共培养系统，并且还可能研究使用 3D 通道网络来传递影响嵌入水凝胶内的干细胞的因子。 公共健康相关性：现代组织工程的进步取决于形成 3D 血管网络的能力，该网络能够为人造组织结构内部的细胞提供营养。使用基于牺牲熔纺微纤维结构的新技术，我们将能够快速且廉价地生产这些网络，从而使患者能够使用所得的血管化人工组织结构。该构建体将由水凝胶（例如明胶）制成，与天然组织非常相似，并且将包含允许该构建体像天然组织一样发挥作用的细胞。