MRI: Development of a Bio-Pick and Place Instrument for the Fabrication of 3D Organs from Complex Shaped Living Building Parts

题目：MRI：一种生物拾取和放置仪器的开发，用于从复杂形状的生活建筑部件中制造3D器官。意义：生物拾取和放置仪器将使布朗大学成为3D器官制造的世界领导者。除了作为生物工程的展示仪器外，Bio-P&amp将是独一无二的，具有独特的技术能力。在布朗大学工程学院，生物医学学部和附属医院已经有一个强大的、资金充足的组织工程师社区，他们将从这种仪器中受益。还有其他教员需要替代动物和新的复杂试验台来评估化学品、纳米材料、新疗法和药物输送的毒性。这种独特的工具将有助于招募未来的教师，并将使新的合作和新的资助机会成为可能（NIH， NSF， DOD，工业）。作为世界一流的仪器，它将促进与学术界、临床医生和工业界的合作。该仪器的开发将产生新的知识产权，并进一步加强生物医学工程中心在生物医学与工程之间建立的协同作用。该文书将大大加强培训基础设施，包括；新一代的仪器学家善于利用工程原理制造各种生物材料，新一代的科学家、工程师和医生使用3D生物结构来研究发育生物学中的问题，减少研究中动物的使用，以及加强组织工程研究、毒理学测试、药物发现、治疗性蛋白质的生产和临床应用。技术描述组织工程领域的主要工程挑战是在体外制造具有高密度活细胞的大型实体器官。为了维持细胞活力，氧气、营养物质的扩散和代谢废物的去除将目前的工程组织的厚度限制在~100-200ìm。天然器官要大得多，并且含有分支血管供应，这些血管供应贯穿整个器官，确保所有细胞都靠近血管。随着组织工程领域与这一限制作斗争，诱导多能干细胞领域为各种组织和器官的免疫匹配细胞提供了丰富的来源。科学界还没有从这种细胞来源中体外制造大型3D器官和组织的方法。具有这种能力的仪器将在组织工程领域产生世界性的影响。这种仪器将在生物制造和生物制造领域建立新的范例，并将为任何基础和应用领域的研究建立新的3D模型。器官制造这一领域的主要挑战是本质上的工程，尽管这些挑战必须由生物学决定。Bio-P&amp；P仪器将使用可控的低水平吸头逐层组装大型3D组织/器官，以拾取活体建筑部件并将其放置在其他活体建筑部件的精确位置上，同时在部件融合和活体结构构建过程中保持灌注。这是一个多功能的建筑平台，可以容纳任何大小、形状和细胞类型的多细胞建筑部件。pi已经生产出了蜂窝状的大型活建筑部件，当堆叠时，这些蜂窝状部件的排列管腔将形成通道，使正在构建的器官能够灌注。成功

PI: Morgan, JeffreyProposal: 1428092Title: MRI: Development of a Bio-Pick and Place Instrument for the Fabrication of 3D Organs from Complex Shaped Living Building PartsSignificanceThe Bio-Pick & Place instrument will make Brown University a world leader in 3D organ fabrication. In addition to being a showcase instrument for bioengineering, the Bio-P&P will be one-of-a-kind with unique technical capabilities. There is already a strong well-funded community of tissue engineers at Brown in the School of Engineering, the Division of BioMed and affiliated hospitals that would benefit from this instrument. There are other faculty in need of a replacement for animals and new complex test beds to evaluate the toxicity of chemicals, nanomaterials, new therapies and drug delivery. This unique instrument will aid in recruiting future faculty and will make possible new collaborations and new funding opportunities (NIH, NSF, DOD, industry). As a world-class instrument, it will foster collaboration with academics, clinicians and industry. Development of the instrument will generate new intellectual property and further strengthen the synergism that the Center for Biomedical Engineering has created between BioMed and Engineering. The instrument will significantly enhance the training infrastructure including; a new generation of instrumentalists facile in the use of engineering principles for the fabrication of a wide range of living materials, a new generation of scientists, engineers, and physicians using 3D living structures to investigate questions in developmental biology, the reduction of the use of animals in research, as well as the enhancement of tissue engineering research, toxicology testing, drug discovery, production of therapeutic proteins and clinical applications.Technical DescriptionThe major engineering challenge to the field of tissue engineering is the in vitro fabrication of large solid organs with high densities of living cells. Diffusion of oxygen, nutrients and removal of metabolic waste products limit current engineered tissues to thicknesses of ~100-200ìm in order to maintain cell viability. Natural organs are much larger and contain a branching vascular supply that perfuses the entire organ and ensures all cells are close to blood vessels. As the field of tissue engineering struggles with this limitation, the field of induced pluripotent (iPS) stem cells is providing a plentiful source of immune-matched cells of a variety of tissues and organs. The community does not yet have a means for the in vitro fabrication of large 3D organs and tissues from this source of cells. An instrument with this capability would have a worldwide impact in the field of tissue engineering. Such an instrument would establish new paradigms in the fields of biofabrication, biomanufacturing and would build new 3D models for research useful in any number of basic as well as applied fields. The major challenges in this area of organ fabrication are engineering in nature, albeit ones that must be informed by biology. The Bio-P&P instrument will assemble large 3D tissues/organs layer-by-layer using a controllable low level suction head to pick up living building parts and place them onto other living building parts in precise locations, while maintaining perfusion as parts fuse and the living structure is built. This is a versatile building platform that can grip multi-cellular building parts of any size, shape and cell type. The PIs have produced large living building parts in the shape of a honeycomb and, when stacked, the aligned lumens of these honeycomb parts will form channels that enable perfusion of the organ under construction. Success