Synthetic hydrogels of poly(ethylene glycol) diacrylate (PEGDA) formed by free-radical photopolymerization have been extensively investigated as extracellular matrix (ECM) mimics for tissue engineering applications. However, the ability to predict and control the spatial and temporal presentation of biochemical and mechanical properties for guiding cell behavior still remains a significant challenge. To this end, we are coupling experimental data with computational modeling in order to determine unknown kinetic parameters and to optimize hydrogel crosslink density and the final biochemical composition of ECM molecules immobilized in the crosslinked network.
The hydrogels were synthesized by visible light free-radical photopolymerization using an Argon Ion laser (λ= 514 nm) in the presence of the crosslinking agent PEGDA, N-vinyl pyrrolidone (NVP), Acrylate-PEG-YRGDS, using the photoinitiator eosinY and the coinitiator triethanolamine (TEA). The photoinitiation mechanism of this photopolymerization system was investigated experimentally through photopolymerization of NVP and precipitation of poly(NVP). The rate of polymerization was measured gravimetrically and the kinetic parameters for this initiation system are obtained from a series of experiments, and applied in the computational models.
Two variants of the mathematical model are presented; the first predicts the molecular weight distribution of the the primary polymer chains that result in hydrogel formation, and the second is a full crosslinking model that predicts hydrogel crosslink density and the incorporation of the cell adhesion ligand YRGDS. Predictions from the first model provide the kinetic parameters that can be used in the crosslinking model. Both models implement the kinetic approach based on the method of moments. The crosslinking model utilizes the Numerical Fractionation technique to circumvent the issue of numerical divergence at the gel point in order to predict the hydrogel crosslink density and the final concentration of YRGDS in the hydrogel. Model predictions agree with experimental data of hydrogel YRGDS incorporation (measured by radiolabeling experiments) and crosslink density (obtained via swelling experiments). The predictive capability of the computational and experimental studies presented will provide invaluable insight for designing scaffolds that dictate cell behavior.