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重要力量，但在活体组织中测量这些力量仍然是一个重大挑战。一种很有前景的方法是在组织中嵌入微型传感器，这些传感器可以被细胞产生的力拉伸、压缩和变形。通过用显微镜记录这些传感器形状的变化，可以测量细胞产生的力随时间的变化。发展这项技术的一个障碍是缺乏坚固、无毒的聚合物材料作为传感器。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解决这一挑战。这项工作的结果将使特定传感应用的水凝胶基材料的设计和制造成为可能，并将建立传感器形状和施加力之间的预测关系。通过该奖项开发的知识和材料将促进它们在组织工程和重建、生物工程设备和医学诊断方面的应用。这个项目将为教育和推广提供重要的机会。将招收生物材料科学与工程专业的研究生和本科生。小学生将有机会实验聚合物，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、工程和医学中的重要性。本项目将理论和实验相结合，开发和优化无毒水凝胶微球，用于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，以实现聚合物水凝胶的机械性能编程，包括分别表现出线性和非线性机械响应的单相和多相材料。这项工作的结果将确定聚合物长度、网络结构、交联密度和疏水含量如何影响材料的剪切弹性和可压缩性。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。传感器的性能将在生物分析中得到验证。这些结果将为开发用于细胞力传感、细胞封装和软组织再生和替代的新型生物相容性水凝胶材料提供基础知识。该奖项反映了美国国家科学基金会的法定使命，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.