Extracellular matrix-mimetic poly(ethylene glycol) hydrogels engineered to regulate smooth muscle cell proliferation in 3-D.

The goal of this project is to engineer a defined, synthetic poly(ethylene glycol) (PEG) hydrogel as a model system to investigate smooth muscle cell (SMC) proliferation in three-dimensions (3-D). To mimic the properties of extracellular matrix, both cell-adhesive peptide (GRGDSP) and matrix metalloproteinase (MMP) sensitive peptide (VPMSMRGG or GPQGIAGQ) were incorporated into the PEG macromer chain. Copolymerization of the biomimetic macromers results in the formation of bioactive hydrogels with the dual properties of cell adhesion and proteolytic degradation. Using these biomimetic scaffolds, the authors studied the effect of scaffold properties, including RGD concentration, MMP sensitivity, and network crosslinking density, as well as heparin as an exogenous factor on 3-D SMC proliferation. The results indicated that the incorporation of cell-adhesive ligand significantly enhanced SMC spreading and proliferation, with cell-adhesive ligand concentration mediating 3-D SMC proliferation in a biphasic manner. The faster degrading hydrogels promoted SMC proliferation and spreading. In addition, 3-D SMC proliferation was inhibited by increasing network crosslinking density and exogenous heparin treatment. These constructs are a good model system for studying the effect of hydrogel properties on SMC functions and show promise as a tissue engineering platform for vascular in vivo applications.