RECODE: Vascular Differentiation and Morphogenesis Controlled with Hybrid Memristors

RECODE：用混合忆阻器控制血管分化和形态发生

• 批准号: 2225601
• 负责人: Donny Hanjaya-Putra
• 金额: $ 150万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2225601&HistoricalAwards=false
• 关键词: RECODE; Vascular; Differentiation; Morphogenesis; Controlled

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.

干细胞组如何区分和形成模式的血管仍然是一个尚未解决的谜团。解决这一挑战将广泛推进生长的组织工程行业，该工程产生可植入的组织和器官。目前的干细胞分化方法昂贵且效率低下。此外，精确的制造三维组织是一个未经满足的挑战。该recode项目将开发和测试一个新的平台，该平台控制电气和化学信号，以将干细胞区分为图案化的血管网络。 该项目将通过研究发现，教育和外展活动影响生物医学界。该团队将在生物学和工程多个领域之间的界面上组织一个多学科会议。为了支持来自代表性不足的团体的受训者，将提供旅行奖，以支付参加会议的费用。为了使STEM劳动力多样化，将在夏季和学期的研究项目中招募来自不同人口背景的本科生。 此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杂交记忆电阻器（MEMRISTOR）和细胞培养装置，以控制人类多能干细胞分化为内皮细胞的分化，并将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中都具有广泛的影响。该平台技术将涉及嵌入一个人工神经元网络，该网络包括备忘录电路以集中和模式的细胞外信号，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此回忆录电路，以与扩展的合成生物学工具包协同作用，其中包括控制细胞信号传导和通过光，合成水凝胶，定量和动态生物标志物测量，分子操纵和机器学习算法的分化。预期的结果包括对化学和生理信号如何影响血管网络的差异和形成的更深入的理解，以及用于较强，可再现和可扩展的细胞类型的可靠，可再现和可扩展产生的新方法。该研究项目由工程生物学和健康开发机制和动物机械机制和物理学机械机机器和生物学机械机机器和生物学机械机械机器和生物学机械机器和动物学机械设置和生物学机械划分共同资助。综合有机系统部门的计划。该奖项反映了NSF的法定任务，并被认为是使用基金会的知识分子优点和更广泛的影响评论标准来评估值得支持的。