(167a) Nanostructured and Dynamic Biomaterials for Controlling the Cell Microenvironment

Kloxin, A. M., University of Delaware

The nano- to macro-scale biophysical and biochemical properties of the environment that surrounds a cell are known to play an important role in cell function and fate. However, less is known about how changes in these properties influence biological functions.  For example, driven by transient bidirectional crosstalk between cells and the extracellular matrix (ECM), cell differentiation and tissue regeneration are complex processes that often involve the presentation of multiple cues that are tightly regulated over multiple time and size scales1. Studying such complex, dynamic processes in vitro remains challenging.  Biomaterials, particularly hydrogels, have emerged as synthetic mimics of the ECM to probe how changes in the microenvironment regulate cell behavior in regeneration or disease2,3.  This talk will focus on strategies to impart highly-regulated property control by synthesizing monomers capable of forming hydrogels in the presence of cells and subsequently allowing triggered modification (e.g., light, enzymes, or reducing conditions) to tune the network’s biophysical or biochemical properties.  Toward mimicking the hierarchical nanostructure of the native ECM, monomers that assemble and allow in situ modification will be presented.  In particular, we will highlight recent results in using these materials to understand the critical cues that direct progenitor cell fate within collagenous tissues during regeneration or disease.

1          Rehmann, M. S. & Kloxin, A. M. Tunable and dynamic soft materials for three-dimensional cell culture. Soft Matter 9, 6737-6746 (2013).

2          Kharkar, P. M., Kiick, K. L. & Kloxin, A. M. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem. Soc. Rev. 42, 7335-7372 (2013).

3          Smithmyer, M. E., Sawicki, L. A. & Kloxin, A. M. Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease. Biomaterials Science 2, 634-650 (2014).