Immobilization and Release of the Redox Mediator Ferrocene Monocarboxylic Acid from within Cross-Linked p(HEMA-co-PEGMA-co-HMMA) Hydrogels

Abstract

Cross-linked hydrogels are synthesized from hydroxyethylmethacrylate (HEMA), polyethyleneglycol methacrylate (PEGMA), and N-[tris(hydroxymethyl)methyl]-acrylamide (HMMA) [p(HEMA-co-PEGMA-co-HMMA) hydrogels] containing 1, 3, 5, 7, 9, or 12 M % of the cross-linker tetraethyleneglycol diacrylate (TEGDA) and are loaded during synthesis with the well-known redox mediator, ferrocene monocarboxylic acid (FcCOOH). In the absence of FcCOOH, the M% TEGDA in deionized (DI) water (48%; 1 mol % TEGDA to 32%; 12 mol % TEGDA) scales with the cross-link density in accordance with Flory-Huggins-Rehner theory. The release profiles of FcCOOH from hydrogel slabs (43.0 mM) into 0.1 M HEPES/0.1 M KCl buffer are determined from the oxidation peak current of FcCOOH via cyclic voltammetry (100 mV/s) and are decidedly Fickian with overall diffusion coefficients that range from 2.64 x 10(-8) cm(2)/s (1 mol % TEGDA) to 4.87 x 10(-9) cm(2)/s (12 mol % TEGDA) and with n parameters that approximated 0.5 but nonetheless linearly declined from 0.49 (1 mol %) to 0.42 (12 mol %). Diffusion coefficients, like hydration, strongly correlate with the M% TEGDA and hence with the cross-link density or the molecular weight (MW) between cross-links. The temperature dependence of the release profiles measured at 10, 15, 20, 25, 30, 35, 40, and 45 degrees C reveal thermally activated transport with activation energies that are 30 kJ/mol (3 mol %), 36 kJ/mol (5 mol %), 45 kJ/mol (7 mol %), 47 kJ/mol (9 mol %) and 57 kJ/mol (12 mol %). Covalent tethering of the FcCOOH via the UV-polymerizable monomers ferrocene monomethacrylate (Fc-AEMA) and ferrocene polyethylene glycol monomethacrylate (Fc-PEG(3500)-AEMA) to produce pendant redox moieties is shown to eliminate or attenuate release of Fc. While, Fc-AEMA showed no evidence of release (0%) from the hydrogel, its PEG-conjugated equivalent, Fc-PEG(3500)-AEMA, shows release of 16% Fc after 5 days of immersion. These hydrogels will serve as the immobilization matrix for oxidoreductase enzymes of biosensors and the parameters obtained used in the modeling of such systems.

Release of Potassium Ion and Calcium Ion from Phosphorylcholine Group Bearing Hydrogels

“…Two phenomenological effects can contribute to the transport of ions out of a hydrogel matrix: diffusion due to concentration gradients and electromigration due to charge density gradients. Diffusion of small, uncharged molecules through neutral hydrogels has been shown to be attenuated by increased crosslinking density which changes the free volume available for transport and can be modeled using porous media or free volume models [15]. Systems such as these have been thoroughly characterized in the literature and reveal a clear linear dependence of crosslink density on crosslinker feed composition [30].…”

“…Of particular importance, ion transport through hydrogels can be used within engineered scaffolds to control cell-matrix and cell-cell interactions in osteoblast cultures [11], in electro-stimulated release of bioactive compounds [12], and to maintain on-eye movement in silicone contact lenses [13]. It has been shown that diffusion in acrylate and methacrylate based hydrogels can be regulated by varying the degree of hydration [14] through the use of bi-functional monomers such as tetra(ethylene glycol) diacrylate (TEGDA) [15].…”

Biomimetic hydrogels gate transport of calcium ions across cell culture inserts

“…Moreover, in so doing, hydrogels may also imbibe other monomeric, reactive, and potentially polymerizable species into its interstices which occupy its void volume and can interact with chain segments or pendant moieties of the host hydrogel (Guiseppi-Elie 2010). Their swelling capacity results in high permeabilities for low molecular weight bioactive molecules (Lin and Metters 2006;Trigo et al 1993), metabolites (Li et al 2004), and redox mediators (Boztas and Guiseppi-Elie 2009). These characteristics have allowed hydrogels to be used in biomedical applications that include biosensors and biochips (Yu et al 2008), drug delivery systems (Kopeček 2010), scaffolds in regenerative medicine (Slaughter et al 2009), as base materials for soft-contact lenses (Russo et al 2007), and as tourniquets (Wilson et al 2010).…”

Vinylferrocene copolymers based biosensors for phenol derivatives

“…However, when P(GMA 85 -co-VFc 15 )/Tyr was used as a working electrode, no reproducible signals were obtained to construct a calibration curve for accurate measurement. Although enzyme binding capacity of the polymer due to the presence of GMA moiety is high, the electroactivity of polymeric film was not sufficient since P(GMA 85 -co-VFc 15 ) was a kind of nonconductive material. In order to construct a conductive composite film, PGA and PPy were covered onto the P(GMA 85 -co-VFc 15 )/Tyr film.…”