(770a) Designing Synthetic Extracellular Matrices for the Creation of Controlled Culture Systems in the Study of Disease

Biomaterials increasingly are used as extracellular matrix (ECM) mimics for controlled cell culture applications. In particular, synthetic hydrogel-based ECMs have been designed that afford precise control of the biophysical and biochemical properties of the matrix for probing cell response and hypothesis testing. Here, we present an approach for the creation of well-defined, hydrogel-based synthetic ECMs formed by light-mediated thiol–ene click chemistry. Matrices with homogeneous nanostructure were formed by photoinitiated step growth polymerization of multi-arm poly(ethylene glycol) functionalized with thiols and cell-degradable peptides functionalized with alkenes (allyloxycarbonyl (alloc)-protected lysine). Hierarchical nanostructures reminiscent of the native ECM were incorporated within these materials using assembling peptides. Self-assembling collagen mimetic peptides based on variants of Proline-Hydroxyproline-Glycine repeats [(POG)_n] were decorated with alloc reactive groups. These multifunctional CMPs assemble to form fibrils ( ~10-250 nm wide, TEM and AFM) that are subsequently ‘locked’ into place by photopolymerization. We are utilizing both the homogeneous and hierarchically-structured matrices for controlled cell culture to study the role of microenvironment cues in cell activation during disease. Specifically, activation of breast cancer cells and fibroblasts in response to microenvironment cues is being examined with these synthetic ECMs toward a better understanding of metastatic disease and fibrosis, respectively.