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

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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.