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.

候选人 自高中以来，我一直在学术实验室进行研究，并且有很长的时间 时间知道我想从事学术界的职业。我有研究 从天文学到环境科学再到应用物理学的领域经验， 我现在专注于利用我在研究生结束时开发的制造技术 学校解决组织工程领域的主要问题。我的兴趣在于 智能材料和生物材料的开发，我认为天然组织本身就是一种 智能材料的最终形式，能够在非常复杂的情况下与环境互动 方式。我不仅对学术界的研究方面感兴趣，而且很关心 关于教学和指导年轻学生；我指导了几个本科生和 硕士学生，帮助指导学生在本科生中的学生研究，并有 自愿参加各种外展计划。在我的博士后经历中 Langer Lab，我将学习成为一名独立调查员所需的技能（例如 提案写作，指导，处理学术官僚机构等），并计划申请 教师的职位在几年内。我还计划了解有关生物医学领域的更多信息 工程以及与之相关的独特问题 环境 该提案的指导阶段讨论的工作将在 MIT的Langer Lab。 Langer Lab被广泛称为一个领先的研究小组之一 广泛的领域，包括药物输送，组织工程，智能材料和生物医学 设备工程。 Langer Lab位于麻省理工学院，这是MIT，这是领先的研究机构之一 该国与几家当地医院建立了牢固的联系。独立阶段 提案将在一所具有强大生物医学工程和材料的大学进行 科学研究计划。 研究（请注意，突出显示的部分包含专有信息） 该提案中讨论的工作重点是开发3D微流体网络 内部水凝胶充当工程组织中的人造血管系统。这样的血管 任何具有重要意义的工程组织都需要网络（临床上有用） 厚度，因为扩散限制了养分和气体传递到细胞的能力 嵌入在脚手架中。 制造技术基于牺牲的使用 由具有pH依赖性溶解度的材料制成的熔体旋转超细纤维网络。 这 以多种方式生产的结构模仿天然毛细管网络，并用 快速，简单，廉价且可扩展的过程。该提案的目的讨论技术 生产所需的结构以及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矩阵中的官能细胞）。 在所有情况下，细胞都将通过介质流过3D通道系统来维持。在 这项工作的指导阶段，将开发脚手架制造技术，并播种 将证明通道壁上的细胞。此阶段还将包含初始工作 优化牺牲技术以允许细胞放置在水凝胶中所需的必要条件， 尽管有可能这个目标可能一直延续到独立阶段。独立 阶段将证明3D网络在含细胞的水凝胶中的制造（首先没有，并且 然后，将通道壁的细胞内衬）。然后，独立阶段将发展共同 这些血管化水凝胶中的培养系统，也可能研究3D的使用 通道网络以交付因素，以影响嵌入水凝胶中的干细胞。