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

非技术描述：人体内发现的组织和器官具有复杂的三维形状，由不同种类的细胞组成。例如，心脏从一个简单的管子发育成一个四腔器官，由心脏成纤维细胞、心肌细胞、平滑肌细胞和内皮细胞组成。这种形状和细胞多样性是在组织发育的早期决定的，干细胞在那里生长并决定它们的命运。在体外，干细胞的命运通常是由改变干细胞的生长条件决定的。然而，另一个重要的变量是力的应用。细胞可以感知它们的环境，在发育过程中拉动和推动组织可能会控制细胞的命运。这将通过在形状变化的材料上生长细胞来实现。这种形状变化的材料将被编程为收缩、弯曲、扭曲和膨胀，以响应刺激来模拟生物组织形成期间发生的自然过程。技术描述：在这项提议中，我们寻求设计形状变形材料作为细胞板培养基质，以开发具有可控形状、细胞组成和细胞形态的人体组织。具体地说，我们建议使用温度响应性水凝胶，因为它们表现出生物相容性，并能够进行平面外编程形状变形。人诱导多能干细胞(HiPSCs)将被种植到温度响应性水凝胶上并允许增殖。然后，温度响应性水凝胶将被加热到生理相关的温度，以诱导平面外形状的变形。一旦形成融合层，温度响应性水凝胶将被冷却，从而使细胞膜能够被排出。材料特性，如硬度、驱动应变和几何形状，对干细胞命运的影响将被探索。对细胞片的形状进行编程的能力是一个重要的研究目标，因为它将(I)提供关于结构和几何在组织发育中所起的作用的见解，(Ii)使细胞在更接近生理环境的结构上增殖，以及(Iii)允许组织工程应用中的细胞片形状选择。这项建议还试图通过向STEM学科介绍代表性不足的少数群体，扩大历来被排除在数学和物理科学之外的成员的参与。这将通过协调一个项目来实现，在该项目中，波士顿地区的科学家将被邀请向来自弱势和代表性不足背景的K-12级别的学生就成为科学家的过程进行演讲。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。

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 by introducing underrepresented minorities to STEM subjects. 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 from disadvantaged and underrepresented backgrounds 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.