NSF-BSF: Development of hydrogel materials for use in cellular force sensing

细胞产生对生长、伤口愈合和许多组织功能至关重要的显著力，但在活组织内测量这些力仍然是一个重大挑战。 一种有希望的方法是在组织内嵌入微观传感器，这些传感器可以通过细胞产生的力拉伸，压缩和变形。通过用显微镜记录这些传感器形状的变化，可以随时间测量细胞产生的力。 开发这项技术的一个障碍是缺乏坚固、无毒的聚合物材料用作传感器。 该项目旨在通过对聚合物组成和加工如何控制水凝胶的结构和机械性能的基本理解来应对这一挑战。这项工作的结果将使水凝胶基材料的设计和制造用于特定的传感应用，并将建立传感器形状和施加的力之间的预测关系。通过该奖项开发的知识和材料将促进其在组织工程和重建，生物工程设备和医疗诊断中的应用。 该项目将为教育和外联提供重要机会。 将招募不同的研究生和本科生群体，并对他们进行生物材料科学和工程方面的培训。小学生将有机会用聚合物进行实验，并了解形状，力学和力之间的关系。将制作和分发课程材料和信息视频，为教师和公众提供资源，以了解和欣赏生物材料科学在生物学，工程学和医学中的重要性。 本项目结合理论和实验，开发和优化无毒水凝胶微球，用作多细胞聚集体和组织中细胞产生的力的传感器。 该研究将建立材料设计标准，使编程的聚合物水凝胶的机械性能，包括单相和多相材料，表现出线性和非线性的机械响应，分别。这项工作的结果将建立如何聚合物长度，网络结构，交联密度和疏水含量影响材料的剪切弹性和压缩性。实验制造方法将被优化，理论模型将被开发，以理解和编程细胞传感应用的材料力学。将在生物测定中确认传感器性能。这些结果将为开发用于细胞力传感、细胞包封和软组织再生和替换的新型生物相容性水凝胶材料提供所需的基础知识。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Cells generate significant forces that are critical to growth, wound healing and many tissue functions, but measuring these forces within living tissues remains a significant challenge. One promising approach is to embed, within the tissue, microscopic sensors that can be stretched, compressed and deformed by cell-generated forces. By recording these sensor shape changes with microscopy, the cell-generated forces can be measured over time. One barrier to developing this technology is the lack of robust, non-toxic, polymeric materials for use as sensors. This project aims to address this challenge by developing a fundamental understanding of how polymer composition and processing control the structural and mechanical properties of hydrogels. The results of this work will enable the design and manufacturing of hydrogel-based materials for specific sensing applications, and will establish predictive relationships between sensor shape and applied force. The knowledge and materials developed through this award will promote their use in tissue engineering and reconstruction, bioengineering devices, and medical diagnostics. This project will provide important opportunities for education and outreach. Diverse cohorts of graduate and undergraduate students will be recruited and trained in biomaterial science and engineering. Elementary school students will be given opportunities to experiment with polymers and learn about the relationships between shape, mechanics and force. Course materials and informational videos will be generated and distributed to provide teachers and the public with resources to understand and appreciate the importance of biomaterials science in biology, engineering and medicine.PART 2: TECHNICAL SUMMARY This project combines theory and experiment to develop and optimize non-toxic hydrogel microspheres for use as sensors of cell-generated forces in multicellular aggregates and tissues. The study will establish the material design criteria that enable programming of the mechanical properties of polymeric hydrogels, including single and multi-phase materials that exhibit linear and nonlinear mechanical responses, respectively. The results of this work will establish how polymer length, network architecture, crosslinking density, and hydrophobic content influence the material’s shear elasticity and compressibility. Experimental manufacturing methods will be optimized and theoretical models will be developed to understand and program the material mechanics for cell sensing applications. Sensor performance will be validated in biological assays. These results will provide the foundational knowledge needed to develop new classes of biocompatible hydrogel materials for cell force sensing, cell encapsulation and soft tissue regeneration and replacement.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.