Designing 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 cells interact with the matrix. The lack of quantitative and predictable information about this process has limited advances in biomaterial design. To bridge this gap, we use microrheology to characterize a matrix metalloproteinase degradable hydrogel both temporally and spatially that is used for three-dimensional human mesenchymal stem cell encapsulation focusing on the region directly around the cell, the pericellular region, during migration. Temporally, we quantify the change in the scaffold rheological properties as the cell degrades the material past the critical gel-sol transition. Spatially we measure the change in the material properties as a function of the distance away from the cell. We also characterize a covalently adaptable hydrogel network and the dynamic transition a cell would experience as the material transforms from a gel to a sol under shear. Once the materials is allowed to relax it will form new covalent bonds and transition back to a gel. These covalently adaptable hydrogels will enable unprecedented environments for cell growth because they yield to cells as they differentiate but reform bonds enabling traction during motility. This work provides a foundation to quantitatively understand dynamic environments that cells reengineer during basic processes enabling design of tunable synthetic materials to enhance and direct cell motility.

Cell-material interactions in synthetic hydrogel scaffolds

249th National Meeting (2015)

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