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: 8727546
• 负责人: Leon Marcel Bellan
• 金额: $ 23.08万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8727546
• 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; career; cell type; clinically significant; experience; high school; interest; melting; methylmethacrylate-methacrylic acid copolymer; outreach program; pressure; prevent; professor; programs; scaffold; skills; tissue support frame; volunteer

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 career in academia as a professor. 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 tissue 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.

侯选人 我从高中开始就在学术实验室做研究，并且已经有很长一段时间了 时间知道我想在学术界追求一份教授的事业。我有研究 从天文学到环境科学再到应用物理等领域的经验，以及 我现在专注于利用我在毕业时开发的一项制造技术 学校解决了组织工程领域的一个重大问题。我的兴趣在于 智能材料和生物材料的发展，我认为自然组织本身是一种 智能材料的终极形式，能够在异常复杂的环境中与其交互 方式。我不仅对学术界的研究方面感兴趣，而且非常关心 关于教学和指导年轻学生；我指导了几个本科生和一个 硕士研究生，本科时在班上帮助指导学生研究，并 志愿参加了各种各样的外展计划。在我的博士后生涯中 Langer Lab，我将学习成为一名独立调查员所需的技能(例如 提案撰写、指导、与学术官僚打交道等)，并计划申请 在几年内获得教员职位。我还计划学习更多关于生物医学领域的知识 工程学，以及与之相关的独特问题 环境 在本建议书的指导阶段讨论的工作将在 麻省理工学院兰格实验室。兰格实验室是广为人知的领先研究小组之一， 广泛的领域，包括药物递送、组织工程、智能材料和生物医学 设备工程学。兰格实验室位于麻省理工学院，是全球领先的研究机构之一。 与当地几家医院有很强的联系。这是独立的阶段 提案将在一所拥有强大生物医学工程和材料的大学执行 科学研究计划。 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3D微流控网络 在水凝胶中作为人造血管系统在工程组织中发挥作用。这样的血管 任何有意义的(和临床上有用的)工程组织都需要网络 厚度，因为扩散限制了营养物质和气体进出细胞的能力 深深地嵌在脚手架里。 制作技术是基于对牺牲材料的使用 熔纺超细纤维网络由具有与pH相关的溶解性的材料制成。 这个 以许多方式产生的结构模仿自然的毛细网络，并且是通过 快速、简单、廉价且可扩展的流程。这份提案的目的是讨论技术 以产生所需的结构，以及在通道壁上播种细胞的技术 (作为内皮衬里)以及水凝胶材料(作为3D基质中的功能细胞)。 在所有情况下，小区都将通过流经3D频道系统的媒体流来维持。在 在这项工作的指导阶段，将开发脚手架制造技术，并 将演示通道壁上的细胞的数量。此阶段还将包含初始工作 有必要优化牺牲技术以允许将细胞放置在水凝胶中， 虽然这一目标可能会一直持续到独立阶段。无党派人士 阶段将演示在细胞水凝胶中构建3D网络(第一次没有，和 然后，单元格也排列在通道壁上)。然后，独立阶段将开发联合- 在这些血管水凝胶中的培养系统，并可能还研究3D的使用 通道网络传递影响嵌入水凝胶中的干细胞的因子。