(494g) Modeling Poly(ethylene glycol) Diacrylate Hydrogel Formed By Eosiny/TEA Visible Light Photopolymerization

Poly(ethylene glycol) diacrylate (PEGDA) hydrogel have been extensively used as extracellular matrix (ECM) mimics for tissue engineering applications. A mathematical model for poly(ethylene glycol) diacrylate (PEGDA) formed by free-radical visible light photo-polymerization is presented. This model describes the light dynamics and predicts the biochemical and mechanical properties in the hydrogel such as the final immobilized composition of ECM molecules and crosslink density which guide cell behavior. This model will help us understand the interaction between each reacting species and direct synthesis of the hydrogel with specific properties by designing the polymerization conditions. The model is based on an extensive experimental investigation of the kinetics and mechanism of photoinitation by EosinY in the presence of amines.

In this study, PEGDA hydrogels are synthesized using visible light (λ = 514 nm) in the presence of the visible light photosensitive dye, EosinY, the co-initiator, triethanolamine (TEA), a comonomer, N-vinyl pyrrolidone (NVP), a crosslinking agent, PEGDA, and an optional PEG monoacrylate monomer that contained the cell adhesive ligand YRGDS. The incorporated YRGDS as well as the physical and mechanical properties of these hydrogels dictate cell behavior and tissue regeneration. The hydrogel properties are tuned through variations in polymerization conditions. Two major parts are included in this study, the first is investigation of the visible light photo-initiation using EosinY and TEA, and the second part is development of a hydrogel synthesis model and validation.

Experiments and modeling were used to determine an expression for the rate of initiation of the EosinY/TEA initiation system and to propose a photoinitiation mechanism. The photoinitiation mechanism is proposed as EosinY absorbing the light and goes to the singlet and then triplet states. In its triplet state, EosinY may react with TEA and generate a primary free radical and a semi-reduced EosinY. The primary free radical initiates the polymerization and the semi-reduced EosinY return to the ground state as the first order or the second order reaction with the primary radical. When EosinY returns to ground state, it regains the light absorption ability and restarts the cycle of generating free radicals. By applying this mechanism, the expression for the rate of initiation was obtained through minimal parameter fitting using the experimental data. The mechanism was validated by additional light absorptions with varied EosinY concentration and incident light intensity, and NVP polymerization measurements. This photo-initiation mechanism was implemented in a hydrogel synthesis model.

The hydrogel synthesis model was developed based on the kinetic approach of the method of moments combined with the Numerical Fractionation Technique. The model was used to predict the hydrogel properties such as gel fraction, crosslink density, and RGD incorporation under various polymerization conditions. Model predictions were compared with experimental data.

The kinetic roles of NVP and PEGDA in the hydrogel synthesis were investigated by the model and by the experiments. The experiments show a maximum in crosslink density as the acrylate to double bond ratio is varied. The maximum occurs near a ratio of 0.5 to 0.6. These observations are confirmed by the model prediction results. The maximum in crosslink density is attributed to the double role played by NVP, as a spacer between crosslinks and as an accelerator. The acceleration effect is related to the synergistic cross-propagation between NVP and PEGDA, which results in an increase of the rate of polymerization and leads to higher crosslink density.

The biochemical and mechanical properties in the hydrogel were also investigated. Model predictions agree with experimental data of hydrogel YRGDS incorporation (measured by radio-labeling experiments) and crosslink density (obtained via swelling experiments). In addition, we addressed some non-idealities in the process of hydrogel synthesis, which can direct model improvement in the future. This model provides insights of the hydrogel synthesis and can be used as a guide for designing a hydrogel with the desired properties for tissue engineering applications.