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Postdoctoral Fellowship: MPS-Ascend: Shape Morphing Materials for Programming Shape, Composition, and Morphology of 3D Cell Sheets

$300,000FY2023MPSNSF

Abdelrahman, Mustafa Kamal, College Station TX

Investigators

Abstract

Non-technical description: Tissues and organs found in the body have complex three-dimensional shapes and are made up of different kinds of cells. For example, the heart develops into a four chambered organ from a simple tube and is composed of cardiac fibroblasts, cardiomyocytes, smooth muscle cells, and endothelial cells. This shape and cellular diversity is determined early during tissue development, where stem cells grow and determine their fate. Outside the body, stem cell fate is typically determined by changing the growing conditions of stem cells. However, another important variable is the application of forces. Cells can sense their environment, and pulling and pushing tissues during development may provide control over cell fate. This will be accomplished by growing cells on a shape changing material. This shape changing material will be programmed to shrink, bend, twist, and expand in response to a stimulus to mimic natural processes that occur during biological tissue formation. Technical description: In this proposal, we seek to engineer shape morphing materials as cell sheet culturing substrates to develop human tissues with controllable shape, cellular composition, and cellular morphology. Specifically, we propose to use thermo-responsive hydrogels as they demonstrate biocompatibility and are capable of out of plane programmed shape deformation. Human induced pluripotent stem cells (hiPSCs) will be seeded onto thermoresponsive hydrogels and allowed to proliferate. Thermoresponsive hydrogels will then be heated to physiologically relevant temperature to induce an out of plane shape deformation. Once confluent layers are developed, the thermoresponsive hydrogel will be cooled, enabling cell sheet expulsion. The effect material characteristics, such as stiffness, actuation strain, and geometry, has on stem cell fate will be explored. The ability to program the shape of cell sheets is an important research target as it will (i) provide insights in the role structure and geometry play in tissue development, (ii) enable cell proliferation on structures that better resemble physiological environments, and (iii) permit cell sheet shape-selection for tissue engineering applications. This proposal also seeks to broaden the participation of members that are historically excluded from the mathematical and physical sciences. This will be accomplished by coordinating a program where scientists in the Boston area will be invited to speak to students at the K-12 level on the process of becoming a scientist. 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.

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