RECODE: Vascular Differentiation and Morphogenesis Controlled with Hybrid Memristors

干细胞群如何分化并形成有图案的血管仍然是一个未解之谜。解决这一挑战将广泛推动不断增长的组织工程行业，生产可植入的组织和器官。目前用于干细胞分化的方法是昂贵且低效的。此外，精确地制造三维组织是一个未满足的挑战。该项目将开发和测试一种新的平台，控制电和化学信号，使干细胞分化为模式化的血管网络。 该项目将通过研究成果、教育和外联活动对生物医学界产生影响。该团队将在生物学和工程学多个领域之间的接口组织一次多学科会议。为支持来自代表人数不足群体的受训人员，将提供旅费，以支付他们出席会议的费用。为了使STEM劳动力多样化，来自不同人口背景的本科生将被招募参加夏季和学期的研究项目。 RECODE项目的总体目标是探索细胞信号传导和生理学如何调节干细胞分化和血管形成的基本机制。为了实现这一目标，多学科研究团队将设计第一个自主混合记忆电阻器（忆阻器）和细胞培养装置，以控制人类多能干细胞分化为内皮细胞及其形态发生为成熟的血管网络。这样的成就将在发育生物学和再生医学方面产生广泛的影响。该平台技术将涉及嵌入一个人工神经网络，该网络包括忆阻器电路，以集中和模式化细胞外信号，并协调通信细胞之间的细胞内振荡。多学科研究团队将设计这种忆阻器电路，以与不断扩展的合成生物学工具包协同作用，其中包括用光、合成水凝胶、定量和动态生物标志物测量、分子操作和机器学习算法控制细胞信号传导和分化。预期成果包括更深入地了解化学和生理信号如何影响血管网络的分化和形成，以及用于分化细胞类型的稳健，可重复和可扩展生产的新方法。该RECODE项目由化学，生物工程，环境和运输系统部门的工程生物学和健康集群共同资助，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

How groups of stem cells differentiate and form patterned blood vessels remains an unresolved mystery. Solving this challenge will broadly advance the growing tissue engineering industry, which produces implantable tissues and organs. Present methods for stem cell differentiation are costly and inefficient. Additionally, manufacturing three-dimensional tissues with precision is an unmet challenge. This RECODE project will develop and test a new platform that controls electrical and chemical signaling to differentiate stem cells into patterned blood vessel networks. This project will impact the biomedical community through research findings and education and outreach activities. The team will organize a multidisciplinary conference at the interface between multiple fields of biology and engineering. To support trainees from underrepresented groups, travel awards will be provided to cover their costs to attend the conference. Toward diversifying the STEM workforce, undergraduate students from diverse demographic backgrounds will be recruited for summer and semester research projects. The overall goal of this RECODE project is to explore the fundamental mechanisms of how cell signaling and physiology regulate stem cell differentiation and vascularization. To achieve this goal, the multidisciplinary research team will engineer the first autonomous hybrid memory resistor (memristor) and cell culture device to control the differentiation of human pluripotent stem cells into endothelial cells and their morphogenesis into mature vascular networks. Such an achievement will have broad implications in both developmental biology and regenerative medicine. The platform technology will involve embedding an artificial neuronal network that includes memristor circuits to concentrate and pattern extracellular signals and coordinate the intracellular oscillations between communicating cells. The multidisciplinary research team will design this memristor circuit to synergize with an expanding synthetic biology toolkit that includes controlling cell signaling and differentiation with light, synthetic hydrogels, quantitative and dynamic biomarker measurements, molecular manipulation, and machine learning algorithms. Expected outcomes include a deeper mechanistic understanding of how chemical and physiological signaling influences the differentiation and formation of vascular networks and new methods for the robust, reproducible, and scalable production of differentiated cell types.This RECODE project is jointly funded by the Engineering Biology and Health Cluster in the Division of Chemical, Bioengineering, Environmental, and Transport Systems, and the Physiological Mechanisms and Biomechanics Program and Animal Developmental Mechanisms Program in the Division of Integrative Organismal Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.