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Hydrogels in endovascular embolization. V. Antitumour agent methotrexate-containing p(HEMA).

The aminohexyl derivative of the copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate (p(HEMA)-Hex) in the form of regular spherical particles was used as a polymeric carrier for chemically sorbed methotrexate (MTX). The effect of the washed p(HEMA)-Hex-MTX carrier on the morphological structure of donor blood, on blood coagulation indicators and on responses of the living tissue surrounding the material which has been in the blood vessel of the rabbit for various periods of time was evaluated. MTX is capable of diffusion for several days from the embolic material.

Animals↗

Fibrin as a matrix for grafting 2-hydroxyethyl methacrylate: preparation and characterization of the graft and its in vivo evaluation for wound healing.

In this work, fibrin was used as a substrate to graft 2-hydroxyethyl methacrylate (HEMA) by free radical polymerization using potassium persulfate and sodium metabisulfite as redox initiators. The extent of grafting the synthetic polymer on the biopolymer was studied under various experimental conditions, and the optimum factors for affording maximum grafting were standardized. The graft, fib-g-p[HEMA], was characterized by Fourier transform infrared, scanning electron microscopy, and X-ray diffraction studies. The graft exhibited a higher shelf life than native fibrin. The biocompatibility of the graft has been tested by in vivo studies and the results, in terms of collagen formation and wound size, proved its suitability for wound healing.

Animals↗

Hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymers for cell microencapsulation: effect of HEMA purity.

Thermoplastic copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) (molar ratio: 75/25 HEMA-MMA) were synthesized using HEMA containing different amounts of ethylene glycol dimethacrylate (EGDMA) to investigate their suitability for cell microencapsulation. Pure HEMA (0.0% EGDMA) was obtained with preparative chromatography to prepare a linear copolymer. Microcapsules (with a diameter of 300-400 microm) were readily made with the copolymers by interfacial precipitation. Smaller and more transparent capsules were obtained using the copolymer prepared from purer HEMA. Chinese hamster ovary (CHO) fibroblasts, as model cells, were microencapsulated in the linear copolymer. The CHO cells survived the microencapsulation process and the metabolic activity of the encapsulated cells increased within the 14 days observation period.

Animals↗

Friction studies of hydrogel contact lenses using AFM: non-crosslinked polymers of low friction at the surface.

The surface of soft contact lenses made of crosslinked poly(2-hydroxyethyl methacrylate). pHEMA, has been investigated with atomic force microscopy in contact mode. The friction force and adhesive force measurements were able to differentiate the non-crosslinked pHEMA chains from the surface of the crosslinked pHEMA networks. These non-crosslinked pHEMA chains at the surface were anchored to the crosslinked pHEMA network, most likely by entanglement and their surfaces were about 2-4nm higher than the surrounding surface in a dehydrated state. In saline solution, the surface friction and adhesive force of the contact lens were significantly reduced compared to those measured for the surface-dehydrated contact lens.

Adhesiveness↗

Dimensionless analysis of swelling of hydrophilic glassy polymers with subsequent drug release from relaxing structures.

Two dimensionless parameters, the diffusional Deborah number, De, and the swelling interface number, Sw, were used as indicators of solvent and solute transport behavior in swellable hydrogel systems. Polymer relaxation and concentration-dependent diffusion led to dynamically swelling polymers which displayed Fickian, Case II, or anomalous transport behavior. Experimental systems studied included crosslinked samples of poly(vinyl alcohol), designated PVA, and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), designated P(HEMA-co-MMA). Model solutes with molecular weights ranging from 200 to 17,000 were used to investigate release properties from these networks. Characteristic polymer relaxation times and swelling front velocities were determined experimentally. To gain an understanding of how polymer morphology and solute properties affected transport behavior, the calculated values of De and Sw were correlated to the diffusional exponent, n, used commonly to indicate the time dependence of sorption and release. The swelling interface number was found to correlate particularly with the transport kinetics, indicating anomalous and Case II solute transport when the Sw values were near 1.0.

Biocompatible Materials↗

Thermal analysis of water in p(HEMA) hydrogels.

Hydrogels composed of poly(hydroxyethyl methacrylate) (pHEMA) and water were investigated using differential thermal analysis (DTA) and adiabatic calorimetry (AC). The results show that the crystallization of water in the gels is a very gradual process, leading to the development of a metastable, non-equilibrium state. They are not in agreement with models that assume the actual presence of thermodynamically different classes of water in the gels, based on the abnormal melting behaviour of this water. The results indicate that the internal structure of these gels can be described as that of an elastic solution, in which the water molecules are distributed continuously over all possible orientations to and interactions with the polymer.

Calorimetry↗

Water-soluble fluorescent diblock nanospheres.

The hydroxyl groups of poly(tert-butyl acrylate)-block-poly(2-hydroxyethyl methacrylate) or PtBA-b-PHEMA were reacted with succinic anhydride to introduce some carboxyl groups into the PHEMA block. Such carboxyl groups were then reacted with Texas-red cadverine (TX-NH(2)) to incorporate dye molecules. The TX-bearing diblocks formed probably spherical micelles in block-selective solvent DMF/toluene containing 2% DMF. "Permanent" micelles or nanospheres were prepared after cross-linking the TX-bearing PHEMA core block. Such nanospheres were made water soluble by cleaving the tert-butyl groups from the PtBA coronas. Water-soluble nanospheres with high TX numbers and fluorescence quantum yields may find applications in fluorescence in situ hybridization assays.

Fluorescent Dyes↗

A new approach to mineralization of biocompatible hydrogel scaffolds: an efficient process toward 3-dimensional bonelike composites.

As a first step toward the design and fabrication of biomimetic bonelike composite materials, we have developed a template-driven nucleation and mineral growth process for the high-affinity integration of hydroxyapatite with a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel scaffold. A mineralization technique was developed that exposes carboxylate groups on the surface of cross-linked pHEMA, promoting high-affinity nucleation and growth of calcium phosphate on the surface, along with extensive calcification of the hydrogel interior. Robust surface mineral layers a few microns thick were obtained. The same mineralization technique, when applied to a hydrogel that is less prone to surface hydrolysis, led to distinctly different mineralization patterns, in terms of both the extent of mineralization and the crystallinity of the apatite grown on the hydrogel surface. This template-driven mineralization technique provides an efficient approach toward bonelike composites with high mineral-hydrogel interfacial adhesion strength.

Biocompatible Materials↗

Silicone rubber-hydrogel composites as polymeric biomaterials. VI. Transport properties in the water-swollen state.

Permeation of inorganic salts in water-swollen silicone rubber-hydrogel composites consisting of a silicone rubber matrix and lightly cross-linked particles of poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-methacrylic acid), poly(methacrylic acid), polyacrylamide or poly(acrylamide-co-methacrylic acid) hydrogels was investigated. The results, together with earlier data on permeation of non-ionic low-molecular-weight substances through the composite materials, were evaluated in terms of the free-volume diffusion theory. It was found that the materials with water content exceeding a certain limit are highly permeable to the salts, and that, as regards permeation properties, they behave as homogeneous water-swollen hydrogels. The dependence of electrical conductivity of the water-swollen composites on the hydrogel phase content was measured, and the results are discussed in relation to other transport properties and to the structure of the materials.

Acrylic Resins↗

A method of relating craniofacial sections to topography in embryos.

The transparent properties of the embedding agent glycol methacrylate facilitate orientation of the complex embryonic craniofacial region. This technique allows for consistent and reproducible section-to-topography orientation. We find it to be a valuable adjunct for envisioning three-dimensional relationships. The contrast of external features of the embryo is enhanced when stained lightly with hematoxylin prior to embedding. The craniofacial region of the embedded embryo is removed with a fine surgical saw and reimbedded. Section-to-topography relationships are readily monitored and documented photographically. Furthermore, it is possible to "preview" sections for symmetry and other considerations of orientation by viewing the cutting face of the block under oblique illumination. A relief image of structures is then visible.

Animals↗

Functional mechanisms of polymer-based in vivo reference electrodes.

We describe a reference electrode catheter based upon a haemocompatible porous liquid junction of poly(2-hydroxyethyl methacrylate) (pHEMA). The diffusion properties of pHEMA rapidly reach a steady state in a variety of physiological environments. To elucidate the functional mechanisms, the transport of ions through pHEMA membranes was studied in electrolyte solutions, plasma solutions and whole blood. Plasma was shown to enhance ion transport by approximately 10% whereas blood decreased transport rates by 40%. The stability of the reference electrode catheter remained within 1 mV over an 8 h period. The mechanisms of stability lie in those material properties of pHEMA which control diffusion, limit protein adsorption and respond to changes in pH, properties which may result in micromechanical fluctuations and subsequent renewal of the polymer/blood interface.

Biocompatible Materials↗

Thermal behavior of poly hydroxy ethyl methacrylate (pHEMA) hydrogels.

The freezing and melting behavior of water in poly hydroxy ethyl methacrylate (pHEMA) hydrogels of different cross-linker and water contents was investigated in relation to the glass transition temperature (Tg) of the gels. After prolonged cooling at -15 degrees C a constant amount of 1.7 mol water per monomeric unit did not freeze, regardless of both the cross-linker and the water content of the gels. At this water content and temperature, pHEMA gels were below their Tg, and the water molecules were prevented from diffusing to the ice crystals formed in the gel. Therefore, the inability of part of the water in pHEMA gels to freeze is not a thermodynamic phenomenon but is caused by kinetic factors.

Chemical Phenomena↗

Immunocytochemical localization of kallikrein in the rat exocrine pancreas.

The subcellular localization of kallikrein was studied in the rat pancreas using the immunocytochemical protein A-gold technique. Kallikrein was found at the level of the rough endoplasmic reticulum (RER), Golgi cisternae, condensing vacuoles, and zymogen granules of the pancreatic acinar cells as well as in the acinar lumen. The effect of various tissue processings on the immunocytochemical labeling of kallikrein was evaluated using pancreatic tissue fixed in glutaraldehyde and embedded in Epon, Lowicryl K4M, or glycol methacrylate (GMA). Compared to the results obtained with Epon, Lowicryl allowed improved resolution and specificity in the immunocytochemical labeling, while GMA retained greater amounts of kallikrein antigenicity leading to a higher intensity in the labeling; since it also gave a good ultrastructural preservation, GMA appeared to be the superior embedding medium for the localization of kallikrein. The quantitative evaluation of the labeling obtained under the three embedding conditions showed the presence of an increasing concentration gradient along the RER-Golgi-granule secretory pathway, suggesting that, like other pancreatic exocrine enzymes, kallikrein is synthesized in the RER, processed through the Golgi apparatus, and packed in the zymogen granules before being released into the acinar lumen.

Animals↗

The influence of various counter ions on the interaction of chlorhexidine with the hydrophilic contact lens polymer, poly(2-hydroxyethyl methacrylate).

The commercially available salts of chlorhexidine were found to interact with the hydrogel poly (2-hydroxyethyl methacrylate) to different extents, the affinity for the polymer decreasing in the order acetate, gluconate, chloride. The uptakes of the acetate and gluconate salts were almost entirely irreversible over the concentration range studied. The influence of some alternative counter ions, namely amino acids and dicarboxylic acid salts, was examined and found to generate a three-fold variation in the extent of the chlorhexidine interaction. Uptakes were greatest for counter ions that were either hydrophobic in character or bore a net negative charge. Only two compounds, glycine and monosodium oxalate, were successful in reducing the extent of sorption below that observed for chlorhexidine hydrochloride.

Acetates↗

Swellable coatings for hearing aid applications.

The problem of acoustic feedback in hearing aids could be solved potentially by applying a compliant hydrogel to the outer surface that would conform to the ear canal and block feedback. With this objective, several formulations of hydrogels were developed and their swelling and mechanical properties investigated. Hydrogel formulations were polymerized from hydroxyethyl methacrylate (HEMA) and N-vinyl-pyrrolidone (NVP), with various photo-initiators, crosslinkers, and swelling agents. The hydrogel that swelled most rapidly and yet remained undissolved in water had a monomer composition of 40 mol% HEMA, 60 mol% NVP, with 1 wt% polyethylene glycol dimethacrylate as a crosslinker, and 0.5 wt% 2,2-dimethoxy-2-phenyl-acetophenone as the photo-initiator. The tensile modulus, strength, hardness, and durability of the dry hydrogels were not a strong function of composition. In the swollen state, the mechanical properties were much reduced. The potential use of these materials on hearing aids has been discussed in this article.

Cross-Linking Reagents↗

Correlations between mouse 3T3 cell spreading and serum fibronectin adsorption on glass and hydroxyethylmethacrylate-ethylmethacrylate copolymers.

The interaction of cells with solid surfaces is important in many settings, including the response of tissue to implanted materials. Protein adsorption to the surface plays a critical role in controlling cell interactions with surfaces. However, few comprehensive studies of both cell behavior and protein adsorption in complex protein mixtures (e.g., serum) have been done so the connection between these events is not well understood. In particular, methods to systematically perturb both protein adsorption and cell behavior in order to understand their relationship have been lacking. To induce changes in cell and protein behavior, the effects of serum dilution and substrate surface chemistry were studied. Surface chemistry was varied by using a series of polymers and copolymers of hydroxyethyl methacrylate (HEMA) and ethylmethacrylate (EMA) varying in their hydrophobic/hydrophilic balance. Large changes in cell spreading and fibronectin adsorption were observed when either serum concentration or polymer type was varied. The spreading of 3T3 cells in serum was found to be well correlated with the amount of fibronectin adsorption to the substrates. Attachment was not correlated with fibronectin adsorption, especially on glass preadsorbed with diluted serum. For 3T3 cells and perhaps other cells that have a receptor for a protein which is present in the medium, the amount of adsorption of this protein to the substrate appears to be a critical factor controlling cell interactions with the substrate.

Adsorption↗

Glucose oxidase sandwiched between pHEMA layers: a continuous flow reactor application.

Glucose oxidase was entrapped between poly(2-hydroxyethyl methacrylate) membranes and conditions were optimized for high enzyme activity and high levels of entrapment. Highest entrapment was with a 78 microns thick coat. A continuous flow membrane reactor was designed and used. The reaction was first order with respect to glucose and to oxygen. Vmax values for the native and immobilized enzymes were 0.182 and 0.133 mM/min. The Km's for native and immobilized enzymes were 6.2 and 16.9 mM, respectively. At high substrate concentrations enzyme poisoning was detected. Both pH and temperature profiles moved to higher values upon immobilization. The enzyme retained 80% of its activity for at least 3 months in dry form.

Catalysis↗

Modification of capillary electrophoresis capillaries by poly(hydroxyethyl methacrylate), poly(diethylene glycol monomethacrylate) and poly(triethylene glycol monomethacrylate).

Modification of capillary electrophoresis (CE) capillaries by poly(hydroxyethyl methacrylate) (poly(HEMA), poly(diethylene glycol monomethacrylate) (poly(DEGMA) and poly(triethylene glycol monomethacrylate) (poly(TEGMA), was studied. Methods based on physical adsorption of the modifier and on its chemical binding were compared on the basis of the electroosmotic flow (EOF) reproducibility, the EOF dependence on the pH, the symmetry of the peak of positively charged tyramine, the stability of the coating and the separation of standard and milk proteins in the modified capillaries. Reproducible coatings were obtained by chemical binding of the polymers to the capillary walls and by coating with a solution of a polymer, as also demonstrated by the atomic force microscopy.

Adsorption↗