Macroporous hydrogels based on 2-hydroxyethyl methacrylate

Four series of macroporous hydrogels based on crosslinked copolymers of 2-hydroxyethyl methacrylate (HEMA)-sodium methacrylate (MANa), copolymer HEMA-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl), terpolymer HEMA-MANa-MOETACl and on a polyelectrolyte complex were used as carriers for immobilization of proteins, chicken egg white albumin and avidin. The adsorption capacity of the hydrogels for the two proteins, kinetics and pH dependence of albumin adsorption and desorption were studied. The morphology of the hydrogels with and without immobilized albumin was studied by low-vacuum scanning electron microscopy.     

Macroporous hydrogels based on 2-hydroxyethyl methacrylate

Crosslinked macroporous hydrogels based on 2-hydroxyethyl methacrylate (HEMA)—[2-(methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl) copolymer, HEMA-MOETACl—methacrylic acid (MA) terpolymer, and on a polyelectrolyte complex of HEMA—MA copolymer with poly(MOETACl) were prepared. All the hydrogels were prepared in the presence of fractionated sodium chloride particles. The hydrogels were characterized by the number of pores and the total volume of all pores in unit volume, the average volume and the average diameter of single pore. Morphology of the hydrogels was investigated by confocal and scanning electron microscopy. The hydrogels based on polyelectrolyte complexes were also characterized by chemical composition. Homogeneous (non-porous) hydrogels with the same composition as macroporous hydrogels were prepared and characterized by their biocompatibility.     

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair

Macroporous hydrogels are artificial biomaterials commonly used in tissue engineering, including central nervous system (CNS) repair. Their physical properties may be modified to improve their adhesion properties and promote tissue regeneration. We implanted four types of hydrogels based on 2-hydroxyethyl methacrylate (HEMA) with different surface charges inside a spinal cord hemisection cavity at the Th8 level in rats. The spinal cords were processed 1 and 6 months after implantation and histologically evaluated. Connective tissue deposition was most abundant in the hydrogels with positively-charged functional groups. Axonal regeneration was promoted in hydrogels carrying charged functional groups; hydrogels with positively charged functional groups showed increased axonal ingrowth into the central parts of the implant. Few astrocytes grew into the hydrogels. Our study shows that HEMA-based hydrogels carrying charged functional groups improve axonal ingrowth inside the implants compared to implants without any charge. Further, positively charged functional groups promote connective tissue infiltration and extended axonal regeneration inside a hydrogel bridge.     

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 4: Growth of rat bone marrow stromal cells in three-dimensional hydrogels with positive and negative surface charges and in polyelectrolyte complexes

The growth of bone marrow stromal cells was assessed in vitro in macroporous hydrogels based on 2-hydro- xyethyl methacrylate (HEMA) copolymers with different electric charges. Copolymers of HEMA with sodium methacrylate (MA⁻) carried a negative electric charge, copolymers of HEMA with [2-(methacryloyloxy)ethyl] trimethylammonium chloride (MOETA⁻) carried a positive electric charge and terpolymers of HEMA, MA⁻ and MOETA⁺ carried both, positive and negative electric charges. The charges in the polyelectrolyte complexes were shielded by counter-ions. The hydrogels had similar porosities, based on a comparison of their diffusion parameters for small cations as measured by the real-time tetramethylammonium iontophoretic method of diffusion analysis. The cell growth was studied in the peripheral and central regions of the hydrogels at 2 hours and 2, 7, 14 and 28 days after cell seeding. Image analysis revealed the highest cellular density in the HEMA-MOETA⁺ copolymers; most of the cells were present in the peripheral region of the hydrogels. A lower density of cells but no difference between the peripheral and central regions was observed in the HEMA-MA⁻ copolymers and in polyelectrolyte complexes. This study showed that positively charged functional groups promote the adhesion of cells.     

Surface modification of hydrogels based on poly(2-hydroxyethyl methacrylate) with extracellular matrix proteins

Infrared attenuated total reflection spectroscopy was used for in situ observation of the deposition of collagen I on poly(2-hydroxyethyl methacrylate-co-methacrylic acid, 2.9%) hydrogels and subsequent attachment of laminin or fibronectin on the collagen surface. While there was no adsorption of collagen dissolved in an acid solution on the hydrogel surface, it deposited on the surface at pH 6.5. The collagen layers with attached laminin or fibronectin were stable on hydrogel surface in physiological solution. The modification with collagen and particularly with collagen and laminin or fibronectin allowed the adhesion and growth of mesenchymal stromal cells and astrocytes on the hydrogel surface.     

Initiated chemical vapor deposition of poly(2-hydroxyethyl methacrylate) hydrogels

Initiated chemical vapor deposition (iCVD), a low temperature variant of hot-wire chemical vapor deposition (HWCVD) is a solvent-free polymerization technique. It was used to synthesize thick, free-standing films of the hydrogel poly(2-hydroxyethyl methacrylate) (PHEMA). In this work, we show that the iCVD technique can yield PHEMA which is free from residual entrained monomer, has low non-specific protein adsorption and is capable of supporting good cell adhesion and proliferation.     

Preferential interactions of calcium ions in poly(2-hydroxyethyl methacrylate) hydrogels

An investigation of the preferential interaction of calcium ions with oxygen atoms in poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogels has been carried out. The formation of polymer–Ca complexes was achieved by exposing powdered or fully hydrated samples with 5 mM, 0.1–0.5 M, or saturated CaCl₂ solutions for certain periods of time. The characteristics of the polymer–Ca complexes were deduced from the effect of the solute on the equilibrium water content, and from NMR, atomic absorption and infrared spectroscopies. The absence of significant changes in the NMR chemical shift and infrared vibrational wavenumbers for the various functional groups confirmed that polymer complexation with Ca²⁺ ions involves only weak interactions, possibly electrostatic or ion–dipole interactions. Among the three types of oxygen atoms in PHEMA, hydroxyl oxygen atoms seem to be the most sensitive to the presence of Ca²⁺ ions. Complexation at the ester oxygen atoms was also evidenced by a new band in the infrared spectra at 1,550 cm^-1. On the other hand, there were no indications that the hydrophobic domains in the backbone and the methyl groups at the side chain of PHEMA interact significantly with Ca²⁺ ions.     

Thermal analysis of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels

The influence of water on the physical properties of a hydrogel is important for understanding natural tissues and in designing synthetic materials to replace them. In this study, poly (2-hydroxyethyl methacrylate) (pHEMA) was used as a model system to understand how water interacts with the polymer of a hydrogel. Thermal analysis methods (thermogravimetric analysis coupled to mass spectrometry and differential scanning calorimetry) were used to determine: (i) the total water content of pHEMA gels; (ii) how this water was lost during heating; (iii) the relationship between water content of the gel and its glass transition temperature; and (iv) the behavior of the water in the gel on cooling. Previous researchers have invoked various models to describe the organization of water in a hydrogel. In this study, the simplest model which could explain all of the results from the different thermal analysis techniques was one which consisted of three classes of water: (i) hydration water in close proximity to the polymer; (ii) interstitial water in regions or cavities surrounded by polymer chains; and (iii) bulk water.     

Synthesis and characterization of hydrogels based on poly(2-hydroxyethyl methacrylate) for drug delivery under UV irradiation

The present study aims to create a controlled release system through the preparation and characterization of hydrogels based on 2-hydroxyl ethyl methacrylate (HEMA). In order to investigate the influence of photo-initiators on the drug release behavior of the resulting hydrogels, three different photo-initiators [2,2-dimethoxy-2-phenyl-acetophenone] (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184) and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) were used. In addition, hydroxyapatite (HAp) was employed to modify HEMA hydrogels. The synthesis of hydrogels was confirmed by characterization through Fourier transform infrared spectroscopy, nuclear magnetic resonance (¹³C NMR) spectroscopy and digital microscope. The responsive behaviors were investigated by recording swelling ratios under different conditions. In vitro drug release studies were performed for donepezil hydrochloride-loaded hydrogels at pH 1.2, 6.8 and 7.4. The results indicated that hydrogels synthesized using Irgacure 2959 released the maximum amount of donepezil hydrochloride. Moreover, the release rate decreased in the presence of HAp.     

Hydrophilic sponges based on 2-hydroxyethyl methacrylate Part VII: Modulation of sponge characteristics by changes in reactivity and hydrophilicity of crosslinking agents

Despite previous unsuccessful attempts to use hydrated poly(2-hydroxyethyl methacrylate) sponges as implantable biomaterials, recently these materials became important as peripheral components in an artificial cornea of the core-and-skirt design. The low mechanical strength of sponges prompted this study on possible improvement of tensile properties by the use of a variety of crosslinking agents. Three vinylic (dimethacrylates) and two allylic compounds were used at different concentrations (0.1 to 2% (mol)) as crosslinking agents in the production of sponges. Their influence on the mechanical properties, porous morphology and swelling behavior of resulting sponges was evaluated. The onset of phase separation during polymerization was also measured by visible spectrophotometry. The results suggested an inherent heterogeneity of sponges, i.e. pores of non-uniform size and structural inhomogeneities. While the effects of changes in the nature and concentration of crosslinking agents on the equilibrium water content of sponges were ambiguous, some of the mechanical properties, such as toughness and elasticity, were improved by crosslinking with allylic agents. Scanning electron microscopic examination suggested that the mechanical effect is related to the variation of size of the polymer particles constituting the sponge structure, which was proved to be dependent upon the onset of phase separation during polymerization. ©2000 Kluwer Academic Publishers     

Micro- and nanoscale modification of poly(2-hydroxyethyl methacrylate) hydrogels by AFM lithography and nanoparticle incorporation

Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels are widely used as biomaterials. Due to their unique combination of biocompatibility and good mechanical properties, they have potential as scaffolds for tissue engineering applications. To this purpose, topographic and chemical patterning at the nano- to the mesoscale is crucial in order to favor and to characterize cell adhesion and proliferation. Here we report the characterization of as-prepared and patterned PHEMA hydrogels, produced by conventional radical polymerization in water and dimethylformamide. We have obtained chemical and morphological micro- and nanoscale patterning by atomic force microscopy based lithography. We also demonstrate that it is possible to incorporate carbon nanoparticles in the hydrogel matrix by supersonic cluster beam deposition.     

Effect of chemical composition on corneal cellular response to photopolymerized materials comprising 2-hydroxyethyl methacrylate and acrylic acid

Characterization of corneal cellular response to hydrogel materials is an important issue in ophthalmic applications. In this study, we aimed to investigate the relationship between the feed composition of 2-hydroxyethyl methacrylate (HEMA)/acrylic acid (AAc) and material compatibility towards corneal stromal and endothelial cells. The monomer solutions of HEMA and AAc were mixed at varying volume ratios of 92:0, 87:5, 82:10, 77:15, and 72:20, and were subjected to UV irradiation. Results of electrokinetic measurements showed that an increase in absolute zeta potential of photopolymerized membranes is observed with increasing the volume ratios of AAc/HEMA. Following 4 days of incubation with various hydrogels, the primary rabbit corneal stromal and endothelial cell cultures were examined for viability, proliferation, and pro-inflammatory gene expression. The samples prepared from the solution mixture containing 0–10 vol.% AAc displayed good cytocompatibility. However, with increasing volume ratio of AAc and HEMA from 15:77 to 20:72, the decreased viability, inhibited proliferation, and stimulated inflammation were noted in both cell types, probably due to the stronger charge–charge interactions. On the other hand, the ionic pump function of corneal endothelial cells exposed to photopolymerized membranes was examined by analyzing the Na⁺,K⁺-ATPase alpha 1 subunit (ATP1A1) expression level. The presence of material samples having higher anionic charge density (i.e., zeta potential of ? 38 to ? 56 mV) may lead to abnormal transmembrane transport. It is concluded that the chemical composition of HEMA/AAc has an important influence on the corneal stromal and endothelial cell responses to polymeric biomaterials.     

Influence of 2-hydroxyethyl methacrylate content on the optical properties of experimental 2-hydroxyethyl methacrylate-added dental glass ionomer

The influence of 2-hydroxyethyl methacrylate (HEMA) on the properties of HEMA-added dental glass ionomer (HAGI) should be determined systematically to develop a smart restorative material. The purposes of this study were to determine the influence of incrementally added HEMA in experimental HAGIs on the color, translucency, opalescence, fluorescence and compressive strength, and to compare with those of commercial resin-modified glass ionomer (RMGI) materials. A varied amount of HEMA (10–50 wt.%) was added into commercial glass ionomer liquid (Fuji II), which was then mixed with three shades of the same glass ionomer powder (shade nos. 21, 22 and 23). RMGIs from the same manufacturer were also investigated. Five specimens, 10 mm in diameter and 2 mm in thickness, were fabricated for each condition. Color of the HAGIs and RMGIs was measured with a reflectance spectrophotometer in the reflectance and the transmittance modes. Translucency, opalescence and fluorescence parameters were calculated. Compressive strength was determined. As the HEMA content increased, CIE L^* value (lightness) decreased while the chroma increased. CIE a^* value showed small and CIE b^* value showed high increase as the HEMA content increased. Increase in translucency was generally dependent on HEMA content except for 30% HEMA condition of shade no. 21. Opalescence decreased as the HEMA content increased while the trend of fluorescence change was shade-dependent. Compressive strength significantly increased after HEMA addition except 50% HEMA condition. The influence of HAMA on the optical properties of HAGIs varied by the shade of powder and the amount of HEMA. For the most relevant simulation of the optical properties of teeth, addition of 30–40% HEMA is recommended when formulating HEMA-added glass ionomers.     

Adsorption of a blood protein on to hydrophilic sponges based on poly(2-hydroxyethyl methacrylate)

Spongy materials of poly(2-hydroxyethyl methacrylate) were synthesized and the adsorption of bovine serum albumin was carried out onto their surfaces. The sponges were characterized by IR spectral analysis, and water sorption property. It was noticed that the chemical architecture of the sponge has a pronounced impact on both the water sorption capacity and adsorption affinity of the sponge surfaces. The adsorption was also studied kinetically and the effect of pH was also investigated. The synthesized sponges were evaluated for antithrombogenic property by performing blood-clot formation tests.     

Polymer brushes on carbon nanotubes by thiol-lactam initiated radical polymerization of 2-hydroxyethyl methacrylate

Water-soluble polymer brushes with multi-walled carbon nanotubes (MWNTs) as backbones were synthesized by grafting 2-hydroxyethyl methacrylate (HEMA) from surface functionalized MWNTs via in situ surface thiol-lactam initiated radical polymerization. MWNTs were functionalized with 2-mercaptoethanol and used as initiators in the polymerization of HEMA in the presence of butyrolactam. FT-IR, XPS, 1H NMR, GPC and TGA were used to determine chemical structure and the grafted polymer quantities of the resulting product. The covalent bonding of PHEMA to the MWNTs dramatically improved the water dispersibility of MWNTs. The average thicknesses of the polymer brushes in the functionalized MWNTs were detected with electron microscopy (SEM and TEM) and images indicated that the nanotubes were coated with polymer layer.     

The synthesis and degradation of collagenase-degradable poly(2-hydroxyethyl methacrylate)-based hydrogels and sponges for potential applications as scaffolds in tissue engineering

A collagenase-cleavable peptide-based crosslinking agent was synthesized and was incorporated into PHEMA sponges, and P[HEMA-co-MeO-PEGMA] gels and sponges [HEMA 2-hydroxyethyl methacrylate, PHEMA = poly(2-hydroxyethyl methacrylate), MeO-PEGMA = poly(ethylene glycol) monomethyl ether methacrylate]. PHEMA and P[HEMA-co-MeO-PEGMA] sponges had polymer droplet morphologies where the dimensions of the morphological features were three to five times larger compared to sponges that were crosslinked with tetraethylene glycol dimethacrylate (TEGDMA), while the P[HEMA-co-MeO-PEGMA] gels had similar morphologies regardless of the crosslinking agent. The differences in the dimensions of the morphologies of the sponges were attributed to differences in hydrophilicities of the crosslinking agent. When incubated in a collagenase solution, PHEMA sponges did not degrade, but P[HEMA-co-MeO-PEGMA] gels took 28 days to degrade and the P[HEMA-co-MeO-PEGMA] sponges took 101 days to degrade to 8% dry weight remaining. A cytotoxicity assay showed that the hydrogels do not elicit any cytotoxic response in vitro.     

Apatite formation on poly(2-hydroxyethyl methacrylate)-silica hybrids prepared by sol-gel process

Hybrids of poly(2-hydroxyethyl methacrylate) (PHEMA), a polymer that has been employed in a wide variety of biomedical applications, and silica-gel, which exhibits a well-known bioactivity, were produced. The obtained hybrids were characterized and their in vitro ability to induce the formation of a calcium phosphate layer on the surface was evaluated. The surface area of hybrids decreased with increasing amounts of PHEMA so that hybrids with more than ~40% PHEMA are virtually non-porous. All hybrids induced the formation of a calcium phosphate layer on their surfaces when soaked into simulated body fluid. The induction time and the morphology of the apatite layer varied according to the polymer content.     

Stabilizer architectures based on fluorinated random and block copolymers for the dispersion polymerization of 2-hydroxyethyl methacrylate in supercritical carbon dioxide

Different types of stabilizers architectures based on copolymers composed of hydrophilic components and CO₂-philic fluorinated acrylate groups were investigated for the free radical dispersion polymerization of 2-hydroxyethyl methacrylate (HEMA) at 65 °C in supercritical carbon dioxide (scCO₂). Four categories of random and block copolymeric stabilizers consisting of 1H,1H,2H,2H-perfluorooctyl methacrylate (FOMA), oligo(ethylene glycol) methacrylate (OEGMA), dimethyl amino ethyl methacrylate (DMAEMA), and ethylene oxide (EO) were selected as stabilizers for HEMA. The effect of the stabilizer architecture on the polymerization results was investigated in terms of stabilizer concentration, the nature of the hydrophilic anchor groups, and block versus random copolymers. White free-flowing poly(HEMA) powders in high yield were obtained with all stabilizers. While the monomer conversion was independent, the morphology of particles was found to be considerably affected by the nature of the stabilizers.     

Study of polymeric interactions of copolymers: 2-hydroxyethyl methacrylate (HEMA) and 2,3-dihydroxypropyl methacrylate (DHPMA) with copper hydroxylated nanoballs

2-hydroxyethyl methacrylate (HEMA) and 2,3-dihydroxypropyl methacrylate (DHPMA) were used to synthesize novel nanocomposites containing 0.5% by weight of copper hydroxylated nanoballs. Glass transition temperatures of the copolymers and their respective nanocomposites were determined by using differential scanning calorimetry (DSC). Thermogravimetric analysis (TGA) was employed to measure the degradation temperatures of the samples and to determine if the degradation is a single step process or multiple step process. The dielectric permittivity (epsilon') and loss factor (epsilon") were measured via Dielectric Analysis (DEA) in the frequency range 0.1 Hz to 100 kHz and between the temperature -150 to 190 degrees C. gamma, beta, and alphabeta conductivity relaxations were revealed using the electric modulus formalism. The activation energies for the relaxations were calculated. Argand plots of M" versus M' were used to study the viscoelastic effects of both copolymer and the composites. Herein we show that it is possible to tune solubility and relaxation properties which are important to the design of new biomaterials.