Copolymers Of 2-hydroxyethyl Methacrylate Research Articles

Nanomechanical analysis of bone tissue engineering scaffolds

Copolymers of (2-hydroxyethyl methacrylate) (HEMA) and methacrylamide monomers conjugated with amino acids were synthesized and crosslinked with ethylene glycol dimethacrylate. The resulting library of copolymers was mineralized in vitro using two distinct methods. In the first mineralization method, the copolymers were polymerized in the presence of a sub-micron hydroxyapatite (HA) suspension. In the second method, copolymers were mineralized with HA using a urea-mediated process. The mechanical properties of all of the copolymers, both mineralized and not, were determined using nanoindentation under both load and displacement control. A power law fit to the initial unloading curve was used to determine a reduced elastic modulus for each material. Between 30 and 300 indentations were performed on each material, and ANOVA analysis was run to determine the statistical significance of differences in modulus between samples. Using nanoindentation, the 22 different samples had reduced modulus values ranging from 840 MPa to 4.14 GPa. Aspartic acid-methacrylate (Asp-MA) copolymers were not distinguishable from the pHEMA control material. Polymerization in the presence of HA created a more uniform material than the urea method of mineralization. Several challenges and solutions encountered in the nanomechanical testing of soft, heterogeneous materials are discussed. These results demonstrate that with proper experimental design, the mechanical properties of tissue engineering scaffold materials based on polymer-ceramic composite materials can be determined using small samples and nanoindentation techniques.

Load-displacement relations for nanoindentation of viscoelastic materials

A model based on the Burgers viscoelastic concept has been developed to describe the nanoindentation behaviors of polymeric materials. An analytical solution of displacement at the indenter tip has been derived based on the analog of the governing equation of elasticity in the time coordinate system to the governing equation of the viscoelastic model in Laplace transform coordinate system. The solution consists of the elastic, viscous, and plastic displacements during loading and unloading. Nanoindentation experiments have been conducted for poly(methyl methacrylate), polycarbonate, hydroxyethyl methacrylate copolymer, amorphous syndiotactic polystyrene, and fast-cure acrylic polymers to provide data for validating the model. The results show excellent agreement between experimental load-displacement data and model prediction for both the loading and unloading before the contact area decreases for all five polymers. The viscosity decreases but the hardness increases with increasing loading rate. Young’s moduli of the interior material obtained by the present study are close to those reported in the literature. Additional analysis showed that the prediction by both the Kelvin and Maxwell viscoelastic models does not agree with the experimental data generated in this study.

Polyethylene glycol‐based cationically charged hydrogel beads as a new microcarrier for cell culture

A new polyethylene glycol (PEG) based microcarrier was designed and examined by the attachment and growth of mouse fibroblast cells. In the design of microcarrier, a PEG-based macromonomer, polyethyleneglycol methacrylate (PEGMA), was selected as the main component of hydrogel beads since PEG is known as a nontoxic and biocompatible material. A relatively new cationic comonomer, N-[3-(dimethylamino)propyl]methacrylamide (DMAPM), with higher ionization ability with respect to the similar comonomers was used for providing cationic charge to the hydrogel structure. In the first part, a suspension copolymerization method was developed for the production of cationically charged hydrogel beads as a potential microcarrier for cell culturing. The suspension copolymerization by using ethylene dimethacrylate (EDM) as cross-linking agent and cyclohexanol as the diluent provided spherical, polydisperse poly(PEGMA-DMAPM-EDM) hydrogel beads with an average size of 121 microm. The hydrogel beads exhibited a pH-dependent swelling behavior. The L929 mouse fibroblast cells were cultured on poly(PEGMA-DMAPM-EDM) hydrogel beads with an initial concentration of 200,000 cells/mL. The cells were incubated in Dulbecco's modified Eagle's medium during 5 days and the cell proliferation was investigated at every 24 h. An effective cell attachment and growth up to 3.5 x 10(6) cells/mL were observed with the poly(PEGMA-DMAPM-EDM) hydrogel beads. The results indicated that the proposed microcarrier was a significant alternative to the hydrogel beads obtained by the copolymerization of 2-hydroxyethyl methacrylate and 2-dimethylaminoethylmethacrylate commonly used in microcarrier-facilitated cell culturing studies.

Microstructure determination of 2-hydroxy ethyl methacrylate and methyl acrylate copolymers by NMR spectroscopy

Copolymers of 2-Hydroxy ethyl methacrylate and methyl acrylate (H/M) of different compositions were synthesized by free radical bulk polymerization using azobisisobutyronitrile (AIBN) as an initiator under nitrogen atmosphere. The copolymers compositions were calculated from 1H NMR spectra. The reactivity ratios for H/M copolymers obtained from a linear Kelen–Tudos method (KT) and nonlinear error-in-variables method (EVM) are r H = 3.31 ± 0.08, r M = 0.23 ± 0.00 and r H = 3.32, r M = 0.23, respectively. The complete spectral assignment of methine, methylene, methyl and carbonyl carbon regions in terms of compositional and configurational sequences of H/M copolymers was done with the help of 13C{ 1H} NMR, distortionless enhancement by polarization transfer (DEPT), two-dimensional heteronuclear single quantum coherence (HSQC) along with total correlated spectroscopy (TOCSY). Further, the assignments of carbonyl region were made with the help of heteronuclear multiple bond coherence (HMBC) spectrum.

Novel flexible network polymers consisting of oligomeric primary polymer chains originated in the mechanistic discussion of multiallyl crosslinking polymerization

It is well known that allyl monomers polymerize only with difficulty and yield polymers having low molecular weights, i.e., oligomers. Inevitably, free-radical multiallyl crosslinking polymerization provides network polymers consisting of oligomeric primary polymer chains, i.e., having abundant dangling chains. This led to the development of novel flexible network polymers such as amphiphilic network polymers (I) consisting of short primary polymer chains and long crosslink units with opposite polarities, simultaneous interpenetrating networks (II) consisting of both polyurethane (PU) and polymethacrylate (PM) networks with oligomeric primary polymer chains, and network polymers (III) consisting of centipede-type primary polymer chains. Thus, the solution copolymerizations of benzyl methacrylate with tricosaethylene glycol dimethacrylate in the presence of lauryl mercaptan yielded I consisting of nonpolar, short primary polymer chains and polar, long crosslink units. The opposite type of I was prepared by the copolymerization of 2-hydroxyethyl methacrylate, a polar monomer having a hydroxyl group, with heneicosapropylene glycol dimethacrylate, a nonpolar monomer having a poly(oxypropylene) unit. The equimolar polyaddition crosslinking reaction of poly(methyl methacrylate-co-2-methacryloyloxyethyl isocyanate) with tri(oxytetramethylene) glycol, leading to PU networks, and the free-radical crosslinking copolymerization of methyl methacrylate with tri(oxytetramethylene) dimethacrylate in the presence of CBr4, leading to PM networks, were progressed simultaneously, providing II formed via the topological crosslink between PU and PM network structures. The post-copolymerizations of oligomeric allyl methacrylate/alkyl methacrylate precopolymers, having different amounts of pendant allyl groups and different molecular weights, with allyl benzoate/vinyl benzoate monomer mixtures were conducted to give III.

Synthesis and Peptide‐Induced Degradation of Biocompatible Fibers Based on Highly Branched Poly(2‐hydroxyethyl methacrylate)

Biocompatible fibers (see figure) are prepared by electrospinning branched poly(2-hydroxyethyl methacrylate) copolymers from methanol. These copolymers contain disulfide branch sites that can be cleaved using tripeptides such as glutathione. Cleavage reduces the copolymer molecular weight substantially, leading to complete fiber dissolution.

New 2‐hydroxyethyl methacrylate resins with good swelling characteristics

Abstract2‐Hydroxyethyl methacrylate copolymers with styrene and series of the cross‐linkers (divinylbenzene and mono‐, di‐ and triethylene glycol dimethacrylates) with low cross‐linking degree (2–5 mol %) were obtained by suspension polymerization. Loading capacity of the resins, their glass transition temperature, and swelling characteristics in 20 solvents were analyzed depending on monomers composition. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1487–1493, 2006

Dielectric analyses of a series of poly(2-hydroxyethyl methacrylate- co-2,3-dihydroxypropyl methacylate) copolymers

The dielectric spectra of a series of copolymers of 2-hydroxyethyl methacrylate (HEMA) and 2,3-dihydroxypropyl methacrylate (DHPMA) were investigated. Recently, the full range dielectric spectrum of poly(2-hydroxyethyl methacrylate) was reported. This study looks at the effects on the dielectric behavior as a result of 2,3-dihydroxypropyl methacrylate addition. The dielectric permittivity, ε′, and the loss factor, ε″, were measured using a dielectric analyzer in the frequency range of 0.6 Hz to 100 kHz and between the temperature range of −150 and 275 °C. The electric modulus formalism was used to reveal the viscoelastic and conductivity relaxations present in the polymers. Several notable changes were observed as 2,3-dihydroxypropyl methacrylate concentration increased. It was observed through DSC and DEA that the glass transition temperature decreased as DHPMA content increased. The secondary dielectric relaxations were also affected as it was recorded that the activation energy for the γ transition increased and the β relaxation decreased with DHPMA content. Ionic conductivity data prove that DHPMA facilitates ionic mobility more efficiently than HEMA.

An Oral Delivery System for Insulin

Crosslinked 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) copolymer hydrogels were studied as drug delivery systems. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Free radical copolymerization of HEMA and MAA with terephthetalic acid (CA) (2, 4, and 6%) as crosslinking agent were carried out at 70°C. The structure of the CA was confirmed by FT-IR, 1H-NMR and 13C-NMR spectroscopy. The composition of the crosslinked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4). The swelling and hydrolytic behavior of the copolymers depended on the content of MAA which caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. It was observed that in acidic media hydrogen bonds formed due to the protonation of the carboxylic acid groups of the MAA while in more basic or neutral conditions electrostatic repulsion occurred between the ionized carboxylic acid groups. This complex behavior affected the macroscopic swelling properties of the resultant hydrogels. The amount of drug release depended on the degree of hydrogel swelling and crosslinking.

Azeotropic Atom Transfer Radical Polymerization of Hydroxyethyl Methacrylate and (Dimethylamino)ethyl Methacrylate Statistical Copolymers and Block Copolymers with Polystyrene

Statistical copolymers of hydroxyethyl methacrylate (HEMA) and (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by atom transfer radical polymerization (ATRP) at the azeotrope in N,N-dimethylformamide (DMF) with controlled molecular weights and molecular weight distributions (generally <1.2). Since the polymerization takes place at the azeotrope, the polymer composition is fixed at the monomer feed composition (HEMA molar composition = 0.718), and there is little compositional drift with total monomer conversion. Poly(HEMA-co-DMAEMA) copolymers were also successfully synthesized from a polystyrene macroinitiator previously made by ATRP. Solution-cast thin films of polystyrene-b-poly(HEMA-co-DMAEMA) amphiphilic diblock copolymers exhibit ordered and periodic nanoscale structures with morphologies that depend on the relative volume fractions and casting solvent used.

Copolymer of 2-hydroxyethyl methacrylate for cerebral arteriovenous malformation: an experimental study

To investigate the feasibility of using methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) to embolize cerebral arteriovenous malformations (AVM). Methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) in the ratio of 9:1 were solved in 16% alcohol so as to make a kind of copolymer (CoHEMA). 12 g glass beads 2 mm in diameter were put into a container so as to construct an in vitro model of AVM. The container was connected with a normal saline bottle via microcatheter. CoHEMA, as embolized, was injected through the microcatheter and the diffusion of CoHEMA was observed till the water flow was stopped. CoHEMA was injected through microcatheter into the pharyngeal ascending arteries near the rete mirabile (RMB) tissue, similar to the human AVM, under digital subtraction angiography until satisfactory embolization was obtained, totally 9 RMB tissues in 7 pigs. Five pigs were injected with normal saline as controls. The pigs were killed 2 days, 2 weeks, and 6 months after embolization respectively and the bilateral RMB tissues were taken out to undergo pathological examination. Nine AVM models in vitro were constructed with the copolymer dispersed symmetrically among the glass beads and stopped the fluid across the model effectively. No copolymer adhered to the wall of microcatheter. Nine RMB tissues of 6 pigs were embolized by using CoHEMA. Six of the seven pigs survived the procedure except one died of too fast injection of copolymer in the primary stage. Follow-up angiography was performed in four pigs and found that no recanalization occurred and the copolymer was diffused in the vessels 80-150 microm in diameter. In the specimens obtained 2 days after embolization, neutrophilic granulocytes scattered surrounding the copolymer, suggesting minor inflammatory reaction. In the specimens obtained 2 weeks after embolization no vessel wall damage and morphological change were found except minor inflammatory reaction inside the vessels and surrounding tissues. In the specimens obtained 2 to 6 months after embolization hyperplasia of connective tissue, minor or mediate chronic inflammatory reaction, and giant cell reaction inside the vessels and surrounding tissues. With low viscosity, better biocompatibility, and embolic instability, and easy to be injected through delivery microcatheter, CoHEMA is an excellent non-adhesive embolic material and can be used in embolic treatment of cerebral AVM.

Novel method of enzymes stabilization on crosslinked thermosensitive carriers

In this paper an immobilization of invertase on thermosensitive copolymers of N-isopropylacrylamide and 2-hydroxyethyl methacrylate or glycidyl methacrylate modified by aminolysis is evaluated. The method is based on the swelling properties of stimuli-sensitive polymers, which work like a pump that sucks up the enzyme on cooling and then on subsequent crosslinking of the enzyme. The attention was focused on the properties of the carrier–enzyme systems, particularly on the effect of crosslinking on their stability. Activity of TG8-NH 2 carrier was very low and independent on concentration of glutaraldehyde used, but carriers TH8 and TH8-NH 2 were more active, especially when 1.0 and 2.5 vol.% of glutaraldehyde were used. It was also observed, that preparations crosslinked by glutaraldehyde were more stable than preparations without crosslinking agent.

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.

Graft Copolymerization of 2-Hydroxyethyl Methacrylate (HEMA) on Persian Silk Yarn

Silk is a highly valued animal fibre that has long been used to produce textiles of the finest quality. During the degumming process it losses almost 30% of its weight. The weighting of silk fibres with mineral compounds is an effective technique to counteract this loss in weight. Chemical modification by graft copolymerization of vinyl monomers is also effective. Persian silk yarn was degummed using Marseille solution soap and graft copolymerized with 2-hydroxyethyl methacrylate (HEMA) in aqueous media by a redox initiator system. The percentage of HEMA in the feed varied from 0-100%. The grafting efficiency obtained was 70-90%. The pH of the medium varied and its effect on the graft copolymerization was investigated. The grafted silk yarn gained in weight as the pH of the copolymerization medium was reduced and the time of copolymerization increased. Grafting affects the mechanical properties of yarn by reducing the tensile strength and slightly increasing the elongation of the yarn. The solubility in a...

Using pH‐sensitive hydrogels containing cubane as a crosslinking agent for oral delivery of insulin

The goal of oral insulin delivery devices is to protect the sensitive drug from proteolytic degradation in the stomach and upper portion of the small intestine. Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) based hydrogels containing 2, 4, and 6% of a crosslinking agent (CA) were studied as drug delivery systems. Cubane-1, 4-dicarboxylic acid (CDA) was linked to two HEMA groups as CA. Radical copolymerizations of HEMA and MAA with the various ratios of CA were performed at 70 degrees C. The compositions of the crosslinked three-dimensional polymers were determined using Fourier transform infrared spectroscopy. Glass-transition temperature of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (pH 1) and simulated intestinal fluid (pH 7.4). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in simulated gastric fluid or an increase in gel swelling in simulated intestinal fluid. The drug-release profiles indicate that the amount of drug release depends on their degree of swelling and crosslinking.

Fluorinated acrylic copolymers: Part II: Polymeric surfactants

A novel series of water insoluble polymeric fluorosurfactants were synthesized by partial esterification of copolymers of hydroxy ethyl methacrylate (HEMA), methyl methacrylate (MMA), 2-ethyl hexyl acrylate (EHA) and butyl acrylate (BA) with tetrafluoro propanoic acid (TFPA) using PTSA as a catalyst and were characterized by IR. The molecular weight of the products was determined by GPC. Flow and wetting properties of these polymeric fluorosurfactants were evaluated in epoxy resins (liquid epoxy and solid epoxy), alkyd paint and powder coatings. Results showed that these polymeric fluorosurfactants could be used as wetting agent, flow additive in alkyd paint, epoxy resins and powder coatings with advantage.

Immobilization of pepsin on an acrylamide/2‐hydroxyethyl methacrylate copolymer and its use in casein hydrolysis

AbstractPepsin was immobilized through covalent bonding on a copolymer of acrylamide and 2‐hydroxyethyl methacrylate via the individual and simultaneous activation of both groups. The extent of enzyme coupling upon the activation of both the amino and hydroxyl groups of the copolymer resulted in a synergistic effect. However, the order of activation of the support was critical. The covalently bound enzyme retained more than 50% of its activity even after six cycles. The storage stability of the covalently bound enzyme was 60% after storage for 1 month, whereas the free enzyme lost all of its activity within 10 days of storage at 35°C. The Michaelis constant (Km) and maximum reaction velocity (Vmax) were 1.1 × 10−6 and 0.87 for the free enzyme and 1.2 × 10−6 and 0.98 for the covalently bound enzyme when the enzyme concentration was kept constant and the substrate concentration was varied. Similarly, Km and Vmax were 6.73 × 10−11 and 0.47 for the free enzyme and 7.59 × 10−11 and 0.545 for the covalently bound enzyme when the substrate concentration was kept constant and the enzyme concentration was varied; this indicated no conformational change during coupling, but the reaction was concentration‐dependent. The hydrolysis of casein was carried out with a fixed‐bed reactor (17 cm × 1 cm). Maximum hydrolysis (90%) was obtained at a 2 cm3/min flow rate at 35°C with a 1 mM casein solution. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1544–1549, 2005

The Relation Between Swelling Properties and Cross-Linking of Hydrogels Designed for Colon-Specific Drug Delivery

Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA)-based hydrogels containing 5% and 10% of a cross-linking agent were studied as drug delivery systems. Terephthalic acid was covalently linked with HEMA, abbreviated as CA (cross-linking agent). Free radical cross-linking copolymerization of HEMA and methacrylic acid (MAA) in three different molar ratios, mixed with a particulate 3, 3-azobis (6-hydroxy benzoic acid) (ABHB) as an azo derivative of 5-aminosalicylic acid with the various ratios CA as cross-linking agent were carried out with using 2, 2, Azobisisobutyronitrile as initiator at the temperature range 60–70°C. The compositions of the cross-linked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing an aqueous buffer solution (pH 7.4 and pH 1) at 37°C. The drug-release profiles indicate that the amount of drug release depends on its degree of swelling and cross-linking.

Biocompatibility of Phema and P(Hema-Co-Sma) Hydrogels

To replace a poly(2-hydroxyethyl methacrylate) (PHEMA) sponge, which has limited applications as an implant material, PHEMA and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) (P(HEMA-co-SMA)) hydrogels with enhanced biocompatibility were prepared based on the copolymerization of 2-hydroxyethyl methacrylate (HEMA) and sodium methacrylate (SMA) at a high monomer concentration. When the cytotoxicity, cell adhesion, and in vivo tissue reaction of the resulting hydrogels were investigated, the results suggest that hydrogels prepared by the copolymerization of HEMA and SMA at a high monomer concentration have great potential as implant materials with an excellent biocompatibility.

In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings

Anti-fouling hydrogel coatings, copolymers of 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidinone, and polyethylene glycol, were investigated for the purpose of improving biosensor biocompatibility. These coatings were modified to incorporate poly(lactide- co-glycolide) (PLGA) microspheres in order to release dexamethasone (DX) and/or vascular endothelial growth factor (VEGF). DX and VEGF release kinetics from microspheres, hydrogels, and microspheres embedded in hydrogels were determined in 2-week and 1-month studies. Overall, monolithic, non-degradable hydrogel drug release had an initial burst followed by release at a significantly lower amount. Microsphere drug release kinetics exhibited an initial burst followed by sustained release for 1 month. Embedding microspheres in hydrogels resulted in attenuated drug delivery. VEGF release from embedded microspheres, 1.1±0.3 ng, was negligible compared to release from hydrogels, 197±33 ng. After the initial burst from DX-loaded hydrogels, DX release from embedded microspheres was similar to that of hydrogels. The total DX release from hydrogels, 155±35 μg, was greater than that of embedded microspheres, 60±6 μg. From this study, hydrogel sensor coatings should be prepared incorporating VEGF in the hydrogel and DX either in the hydrogel or in DX microspheres embedded in the hydrogel.