3D Microvascular Networks in Hydrogels Fabricated with Sacrificial Structures

候选 我从高中起就一直在学术实验室做研究， 我早就知道我想在学术界当教授。我有研究 在天文学、环境科学和应用物理学等领域的经验， 我现在专注于开发我在研究生毕业时开发的制造技术 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就是一种 智能材料的最终形式，能够以极其复杂的方式与环境相互作用， 的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;我已经指导了几个本科生和一个 硕士研究生，帮助指导学生在一个班的研究作为一个本科生，并已 志愿参加了各种各样的外展项目在我的博士后经历中， 兰格实验室，我将学习必要的技能，成为一个独立的调查员（如 提案撰写、指导、处理学术官僚机构等），并计划申请一个 几年之内的教师职位。我还计划学习更多关于生物医学领域的知识 工程，以及与之相关的独特问题 环境 本建议书指导阶段讨论的工作将在 麻省理工学院兰格实验室。兰格实验室是众所周知的领先研究小组之一， 广泛的领域，包括药物输送，组织工程，智能材料和生物医学 设备工程兰格实验室位于麻省理工学院，是世界领先的研究机构之一。 与当地几家医院有着密切的联系。独立阶段 建议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） 本提案中讨论的工作重点是开发3D微流体网络 在水凝胶中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（和临床有用）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 深嵌在脚手架里 该制造技术是基于使用牺牲 由具有pH依赖性溶解度的材料制成的熔纺微纤维网络。 的 以多种方式产生的结构模仿天然毛细血管网络，并且用 快速、简单、廉价和可扩展的过程。本提案的目的是讨论技术 以及在通道壁上接种细胞的技术 (as内皮衬里）以及在水凝胶材料中（作为3D基质中的功能细胞）。 在所有情况下，细胞将由通过3D通道系统的培养基流维持。在 在这项工作的指导阶段，将开发支架制造技术，并播种 将展示通道壁上的细胞。这一阶段还将包括初步工作 优化牺牲技术以允许细胞被放置在水凝胶中是必要的， 尽管这一目标可能会持续到独立阶段。独立 阶段将展示在载有细胞的水凝胶中制造3D网络（首先没有， 然后细胞也衬在通道壁上）。独立阶段将共同发展， 培养系统在这些血管化水凝胶，也可以研究使用的3D 通道网络以递送影响包埋在水凝胶内的干细胞的因子。

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.