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MATHEMATICAL MODELING OF POLY(ETHYLENE GLYCOL) DIACRYLATE HYDROGEL SYNTHESIS VIA VISIBLE LIGHT FREE-RADICAL PHOTOPOLYMERIZATION FOR TISSUE ENGINEERING APPLICATIONS

Creator

Lee, Chu-yi

Date

2013, 2013-05

Description

Crosslinked hydrogels of poly(ethylene glycol) diacrylate (PEGDA) have been extensively used as scaffolds for applications in tissue...
Show moreCrosslinked hydrogels of poly(ethylene glycol) diacrylate (PEGDA) have been extensively used as scaffolds for applications in tissue engineering. In this thesis, PEGDA hydrogels are synthesized using visible light free-radical photopolymeriza- tion (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 contains the cell adhesive ligand YRGDS. The incorporation level of the YRGDS lig- and as well as the physical and mechanical properties of these hydrogels dictate cell behavior and tissue regeneration. These hydrogel properties may be tuned through variations in polymerization conditions. The goal of this thesis was to develop a math- ematical model for PEGDA hydrogel formation which predicts the incorporation level of YRGDS and the crosslink density of hydrogel as a variety of polymerization con- ditions. This model provides insight into the process of hydrogel crosslinking and in effectively guiding the experimental design of these scaffolds for tissue engineering applications. To accomplish this task two major components comprised the studies of this thesis. The first component involved an investigation of the visible light photo- initiation mechanism of EosinY and TEA, and the second component involved the develop of a hydrogel synthesis model and its 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. In Chapter 2, exper- imental data and parameter fitting were utilized to obtain an empirical expression for the rate of initiation. However, this empirical expression did not consider the ef- fect of inhomogeneous light distribution which is present in this experimental system. The dynamics of light absorption during polymerization were measured under differ- xiv ent conditions in order to gain insight into the kinetic photoinitiation mechanism as well as the rate of initiation. In Chapter 3, a mechanism for this photo-initiation was proposed. Using this mechanism the light absorption dynamics accounting for inhomogeneous light distribution were simulated which were found to be in an agree- ment with the light absorption measurements shown in Chapter 2. Further validation of this proposed mechanism was achieved from polyNVP conversion measurements. This photo-initiation mechanism was implemented in the hydrogel model. In Chapter 4, 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 dynamics of hydrogel properties such as gel fraction, crosslink density, and RGD incorporation under various polymerization conditions. Model predictions were compared with experimental data. Three sets of experiments were conducted. In the first set of experiments where hydrogels were formed in the absence of Acryl-PEG-RGD, the total double bond concentration was kept constant while varying the compositions of NVP and PEGDA. The model and the experiments showed a maximum crosslink density for an acrylate to double bond ratio of 0.5 to 0.6. This is related to the synergistic cross-propagation between NVP and PEGDA, which results in an increase in the rate of polymerization leading to higher crosslink density. In the second set of experiments, hydrogels were formed in the presence of Acryl-PEG-RGD to investigate its incorporation as well as the hydrogel crosslink density. The model showed reasonable agreement with the experimental data and in some cases the predicted RGD deviated from the experimental measurements due to changes in volume upon swelling. The effect of swelling was not considered by the model. The calculated crosslink densities were compared with the inverse swelling ratios from the experiments. The reduction of free volume due to the space occupied xv by the unreacted pendant double bonds was not considered by the model. This reduc- tion of free volume affected the apparent swelling ratio obtained from experiments thus resulting in the observed mismatch between the experimental trends and the predicted crosslink density by the model. In the third set of experiments, additional crosslink density measurements were conducted using a PEGDA macromer of lower molecular weight (MW = 575 Da.). The experiments were performed in the absence of Acryl-PEG-RGD. Few cases were not accurately predicted since the model did not consider the reduction in the concentration of available pendant double bonds when gelation occurs. Among the three set of experiments, the hydrogel synthesis model offers reasonable predictions for most of the experimental cases. This model can be used as a guide for experimen- tally designing PEGDA hydrogels with the desired properties for tissue engineering applications.
PH.D in Chemical and Biological Engineering, May 2013
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