Water Diffusion and Uptake in Injectable ETTMP/PEGDA Hydrogels

Abstract

Differential scanning calorimetry (DSC) and pulsed field gradient spin echo nuclear magnetic resonance (PFGSE NMR) were used to characterize water in hydrogels of ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA). Freezable and nonfreezable water were quantified using DSC; water diffusion coefficients were measured using PFGSE NMR. No freezable water (free or intermediate) was detected from DSC for hydrogels of 0.68 and greater polymer mass fractions. Water diffusion coefficients, from NMR, decreased with increasing polymer content and were assumed to be weighted averages of free and bound water contributions. Both techniques showed decreasing ratios of bound or nonfreezable water mass per polymer mass with increasing polymer content. Swelling studies were used to quantify the equilibrium water content (EWC) to determine which compositions would swell or deswell when placed in the body. At 30 and 37 °C, fully cured, non-degraded ETTMP/PEGDA hydrogels at polymer mass fractions of 0.25 and 0.375, respectively, were shown to be at EWC.

Scheme 1. Thiol-Ene Michael Addition of ETTMP and PEGDA to Form a Hydrogel Network

Figure 1

Mass of free water present per mass of gel in hydrogels of varying polymer mass fractions, obtained with DSC measurements of the freezing peaks of water in hydrogels of varying polymer mass fractions (n = 3; ±standard error). Inset: DSC curve for the melting peak of water in the hydrogel at a polymer mass fraction of 0.25.

Figure 2

Spectrally resolved T₂ relaxation times of water in hydrogels of varying polymer mass, as measured via NMR at 25 °C.

Figure 3

Diffusion coefficients of water measured via NMR at 25, 30, and 37 °C for hydrogels of varying polymer mass fraction. The values of 0.30 and 0.40 are the averages of two samples. The inset image shows the NMR tube of the clear hydrogel at a polymer mass fraction of 0.30 above a layer of expelled water, after measurements at 37 °C; the arrow indicates the interface between expelled water and hydrogel.

Figure 4

Comparison of the mass of bound water present per mass of the polymer obtained via NMR (diffusion) and DSC (freezing; n = 3; ±standard error) measurements for said hydrogels.

Figure 5

Fraction of initial mass of hydrated hydrogels, , present after 24 h in PBS at 25, 30, and 37 °C. (n = 3; vertical error bars represent ± standard error; horizontal error bars extend to the average polymer mass fraction obtained from lyophilized hydrogel mass (v. nominal masses as prepared); and the dotted line indicates EWC).