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促进不断增长的组织工程行业，该行业生产可植入的组织和器官。目前干细胞分化的方法既昂贵又低效。此外，制造精确的三维组织是一项尚未满足的挑战。这个Recode项目将开发和测试一种新的平台，该平台控制电气和化学信号，以将干细胞分化为图案化的血管网络。该项目将通过研究成果以及教育和推广活动对生物医学界产生影响。该团队将在生物学和工程学的多个领域之间的交界处组织一次多学科会议。为支持来自代表人数不足的团体的受训人员，将提供旅费奖励，以支付他们参加会议的费用。为了使STEM劳动力多样化，将招募来自不同人口背景的本科生参加夏季和学期的研究项目。这个Recode项目的总体目标是探索细胞信号和生理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出第一个自主混合记忆电阻器(Memristor)和细胞培养装置，以控制人类多能干细胞向内皮细胞的分化以及其向成熟血管网络的形态发生。这样的成就将在发育生物学和再生医学中产生广泛的影响。平台技术将涉及嵌入一个人工神经元网络，该网络包括记忆阻器电路，以集中和处理细胞外信号，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，以与不断扩大的合成生物学工具包协同工作，该工具包包括用光控制细胞信号和分化、合成水凝胶、定量和动态生物标记物测量、分子操作和机器学习算法。预期成果包括对化学和生理信号如何影响血管网络的分化和形成的更深入的机械理解，以及用于稳健、可重复和可扩展生产分化细胞类型的新方法。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以及综合组织系统部门的生理机制和生物力学计划和动物发育机制计划联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。