Rheological Characterization of Cellularly Remodeled Hydrogel Matrices

1236662 anseth设计支架来模拟细胞外基质，并提供一个可以在迁移过程中被细胞重塑的3D微环境，已经成为伤口愈合、组织工程和干细胞扩增中越来越受关注的应用领域。尽管这些材料为细胞提供了一个最初定义良好的微环境，但人们对迁移细胞如何降解和改造合成支架知之甚少。关于这一过程的定量和可预测信息的缺乏限制了生物材料设计的进步。为了弥补这一差距，通过使用宏观和微观流变测量来表征被封装细胞重塑的3D水凝胶基质，将能够在细胞迁移开始之前和迁移期间对细胞周围区域（细胞周围区域）的材料特性进行定量评估。具体来说，我们建议通过实验来确定降解反应过程中材料性能和支架非均质性的长度尺度。体流变学将用于补充微流变学，从而能够测量完整的凝胶反应。最后，在囊化迁移细胞系（特别是人间充质干细胞）存在的情况下进行测量，以更好地了解细胞周围区域的流变变化如何与细胞形态、局灶黏附和运动性相关。这种理解细胞迁移的方法，专注于水凝胶内部的基本流变变化，有可能改变许多领域，包括但不限于软材料的流变学、3D细胞培养、组织再生和生物材料开发。更广泛的影响：在这些研究中获得的信息将增加对迁移过程中细胞重塑的认识。拟议的研究将对包括伤口愈合、组织工程和干细胞培养在内的几个领域的智力进步和更广泛的技术发展产生重大影响。这将通过推进生物材料的发展来造福社会，这些生物材料可以控制细胞的功能、运动和形态。这项工作的结果将在学术论文和会议发言中传播。这个多学科项目将培训研究生和本科生，并特别努力从代表性不足的群体中招收学生。这些学生将进行研究，以实现这个项目的目标，这个研究也将与社区分享。PI和她的研究小组有广泛接触高中学生和教师以及公众的历史，该团队将努力突出生物材料科学在社会中的影响。

1236662AnsethDesigning scaffolds to mimic the extracellular matrix and provide a 3D microenvironment that can be remodeled by cells during migration has been an area of growing interest with applications in wound healing, tissue engineering and stem cell expansion. Although such materials provide an initially well-defined microenvironment for the cells, little is known about how migrating cells degrade and remodel synthetic scaffolds. The lack of quantitative and predictable information about this process has limited advances in biomaterial design. To bridge this gap, characterizing a 3D hydrogel matrix remodeled by encapsulated cells using both macro- and microrheological measurements will enable quantitative evaluation of the material properties in the region directly around the cell, the pericellular region, before the onset of and during cell migration. Specifically, we propose experiments to determine material properties and the length scale of scaffold heterogeneity during the degradation reaction. Bulk rheology will be used to supplement microrheology enabling measurements of the complete gelation reaction. Finally, measurements conducted in the presence of an encapsulated migratory cell line, specifically human mesenchymal stem cells, will be performed to better understand how rheological changes in the pericellular region correlate with cell morphology, focal adhesions and motility. This approach to understanding cell migration, focusing on the fundamental rheological changes within the hydrogel, has the potential to transform many fields including but not limited to rheology of soft materials, 3D cell culture, tissue regeneration and biomaterials development.Broader impacts: The information gained during these studies will increase knowledge about cell remodeling during migration. The proposed research will have a significant impact on the intellectual advances and broader technological developments in several fields including wound healing, tissue engineering and stem cell culture. This will benefit society by advancing the development of biomaterials that can control cellular function, motility and morphology. The results of this work will be disseminated in academic papers and conference presentations. This multidisciplinary project will train students, graduate and undergraduate, with special efforts to recruit students from underrepresented groups. These students will perform research to meet the goals of this project, and this research will also be shared with the community. The PI and her research group have a history of extensive outreach to high school students and teachers and the general public, and the team will work to highlight the impact of biomaterial science in society.