RECODE: Vascular Differentiation and Morphogenesis Controlled with Hybrid Memristors

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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.