Search tips
Search criteria

Results 1-25 (129018)

Clipboard (0)

Related Articles

1.  Performance of a Cyanobacteria Whole Cell-Based Fluorescence Biosensor for Heavy Metal and Pesticide Detection 
Sensors (Basel, Switzerland)  2013;13(5):6394-6404.
Whole cell biosensors always face the challenge of low stability of biological components and short storage life. This paper reports the effects of poly(2-hydroxyethyl methacrylate) (pHEMA) immobilization on a whole cell fluorescence biosensor for the detection of heavy metals (Cu, Pb, Cd), and pesticides (dichlorophenoxyacetic acid (2,4-D), and chlorpyrifos). The biosensor was produced by entrapping the cyanobacterium Anabaena torulosa on a cellulose membrane, followed by applying a layer of pHEMA, and attaching it to a well. The well was then fixed to an optical probe which was connected to a fluorescence spectrophotometer and an electronic reader. The optimization of the biosensor using several factors such as amount of HEMA and drying temperature were undertaken. The detection limits of biosensor without pHEMA for Cu, Cd, Pb, 2,4-D and chlorpyrifos were 1.195, 0.027, 0.0100, 0.025 and 0.025 μg/L respectively. The presence of pHEMA increased the limits of detection to 1.410, 0.250, 0.500, 0.235 and 0.117 μg/L respectively. pHEMA is known to enhance the reproducibility of the biosensor with average relative standard deviation (RSD) of ±1.76% for all the pollutants tested, 48% better than the biosensor without pHEMA (RSD = ±3.73%). In storability test with Cu 5 μg/L, the biosensor with pHEMA performed 11.5% better than the test without pHEMA on day-10 and 5.2% better on day-25. pHEMA is therefore a good candidate to be used in whole cell biosensors as it increases reproducibility and enhances biosensor storability.
PMCID: PMC3690062  PMID: 23673679
whole cell biosensor; pHEMA; heavy metals; pesticides
2.  Biocompatible Bacterial Cellulose-Poly(2-hydroxyethyl methacrylate) Nanocomposite Films 
BioMed Research International  2013;2013:698141.
A series of bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite films was prepared by in situ radical polymerization of 2-hydroxyethyl methacrylate (HEMA), using variable amounts of poly(ethylene glycol) diacrylate (PEGDA) as cross-linker. Thin films were obtained, and their physical, chemical, thermal, and mechanical properties were evaluated. The films showed improved translucency compared to BC and enhanced thermal stability and mechanical performance when compared to poly(2-hydroxyethyl methacrylate) (PHEMA). Finally, BC/PHEMA nanocomposites proved to be nontoxic to human adipose-derived mesenchymal stem cells (ADSCs) and thus are pointed as potential dry dressings for biomedical applications.
PMCID: PMC3777182  PMID: 24093101
3.  Removal of Co(II), Cu(II) and Pb(II) ions by polymer based 2-hydroxyethyl methacrylate: thermodynamics and desorption studies 
Removal thermodynamics and desorption studies of some heavy metal ions such as Co(II), Cu(II) and Pb(II) by polymeric surfaces such as poly 2-hydroxyethyl methacrylate (PHEMA) and copolymer 2-hydroxyethyl methacrylate with monomer methyl methacrylate P(MMA-HEMA) as adsorbent surfaces from aqueous single solution were investigated with respect to the changes in pH of solution, adsorbent composition, contact time and temperature in the individual aqueous solution. The linear correlation coefficients of Langmuir and Freundlich isotherms were obtained and the results revealed that the Langmuir isotherm fitted the experiment results better than Freundlich isotherm. Using the Langmuir model equation, the monolayer removal capacity of PHEMA surface was found to be 0.7388, 0.8396 and 3.0367 mg/g for Co(II), Cu(ΙΙ) and Pb(II) ions and removal capacity of P(MMA-HEMA) was found to be 28.8442, 31.1526 and 31.4465 mg/g for Co(II), Cu(ΙΙ) and Pb(II) ions, respectively. Changes in the standard Gibbs free energy (ΔG0), standard enthalpy (ΔH0) and standard entropy (ΔS0) showed that the removals of mentioned ions onto PHEMA and P(MMA-HEMA) are spontaneous and exothermic at 293–323 K. The maximum desorption efficiency was 75.26% for Pb(II) using 0.100 M HNO3, 70.10% for Cu(II) using 0.100 M HCl, 59.20% for 0.100 M HCl 63.67% Co(II).
PMCID: PMC3561097  PMID: 23369255
Removal; Polymeric surfaces; Langmuir isotherm; Heavy metal ions; Thermodynamics parameters
4.  Construction of paclitaxel-loaded poly (2-hydroxyethyl methacrylate)-g-poly (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer nanoparticle delivery system and evaluation of its anticancer activity 
There is an urgent need to develop drug-loaded biocompatible nanoscale packages with improved therapeutic efficacy for effective clinical treatment. To address this need, a novel poly (2-hydroxyethyl methacrylate)-poly (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine [PHEMA-g-(PLA-DPPE)] copolymer was designed and synthesized to enable these nanoparticles to be pH responsive under pathological conditions.
The structural properties and thermal stability of the copolymer was measured and confirmed by Fourier transform infrared spectroscopy, nuclear magnetic resonance, and thermogravimetric analysis. In order to evaluate its feasibility as a drug carrier, paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles were prepared using the emulsion-solvent evaporation method.
The PHEMA-g-(PLA-DPPE) nanoparticles could be efficiently loaded with paclitaxel and controlled to release the drug gradually and effectively. In vitro release experiments demonstrated that drug release was faster at pH 5.0 than at pH 7.4. The anticancer activity of the PHEMA-g-(PLA-DPPE) nanoparticles was measured in breast cancer MCF-7 cells in vivo and in vitro. In comparison with the free drug, the paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles could induce more significant tumor regression.
This study indicates that PHEMA-g-(PLA-DPPE) nanoparticles are promising carriers for hydrophobic drugs. This system can passively target cancer tissue and release drugs in a controllable manner, as determined by the pH value of the area in which the drug accumulates.
PMCID: PMC3299577  PMID: 22419875
poly (2-hydroxyethyl methacrylate); controlled release; biocompatibility; antitumor activity; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine; nanoparticles
5.  Combinatorial Design of Hydrolytically Degradable, Bone–like Biocomposites Based on PHEMA and Hydroxyapatite 
Polymer  2012;54(2):909-919.
With advantages such as design flexibility in modifying degradation, surface chemistry, and topography, synthetic bone–graft substitutes are increasingly demanded in orthopedic tissue engineering to meet various requirements in the growing numbers of cases of skeletal impairment worldwide. Using a combinatorial approach, we developed a series of biocompatible, hydrolytically degradable, elastomeric, bone–like biocomposites, comprising 60 wt% poly(2–hydroxyethyl methacrylate–co–methacrylic acid), poly(HEMA–co–MA), and 40 wt% bioceramic hydroxyapatite (HA). Hydrolytic degradation of the biocomposites is rendered by a degradable macromer/crosslinker, dimethacrylated poly(lactide–b–ethylene glycol–b–lactide), which first degrades to break up 3–D hydrogel networks, followed by dissolution of linear pHEMA macromolecules and bioceramic particles. Swelling and degradation were examined at Hank’s balanced salt solution at 37 °C in a 12–week period of time. The degradation is strongly modulated by altering the concentration of the co–monomer of methacrylic acid and of the macromer, and chain length/molecular weight of the macromer. 95% weight loss in mass is achieved after degradation for 12 weeks in a composition consisting of HEMA/MA/Macromer = 0/60/40, while 90% weight loss is seen after degradation only for 4 weeks in a composition composed of HEMA/MA/Macromer = 27/13/60 using a longer chain macromer. For compositions without a co–monomer, only about 14% is achieved in weight loss after 12–week degradation. These novel biomaterials offer numerous possibilities as drug delivery carriers and bone grafts particularly for low and medium load–bearing applications.
PMCID: PMC3601847  PMID: 23525786
pHEMA; hydrolytic degradation; macromer
6.  3D Microperiodic Hydrogel Scaffolds for Robust Neuronal Cultures 
Advanced functional materials  2011;21(1):47-54.
Three-dimensional (3D) microperiodic scaffolds of poly(2-hydroxyethyl methacrylate) (pHEMA) have been fabricated by direct-write assembly of a photopolymerizable hydrogel ink. The ink is initially composed of physically entangled pHEMA chains dissolved in a solution of HEMA monomer, comonomer, photoinitiator and water. Upon printing 3D scaffolds of varying architecture, the ink filaments are exposed to UV light, where they are transformed into an interpenetrating hydrogel network of chemically cross-linked and physically entangled pHEMA chains. These 3D microperiodic scaffolds are rendered growth compliant for primary rat hippocampal neurons by absorption of polylysine. Neuronal cells thrive on these scaffolds, forming differentiated, intricately branched networks. Confocal laser scanning microscopy reveals that both cell distribution and extent of neuronal process alignment depend upon scaffold architecture. This work provides an important step forward in the creation of suitable platforms for in vitro study of sensitive cell types.
PMCID: PMC3120232  PMID: 21709750
Tissue Engineering; 3D Cell Culture; Hippocampal Neurons; Direct-Write Assembly
7.  Correlation of histological findings with gadolinium enhanced MRI scans during healing of a PHEMA orbital implant in rabbits 
BACKGROUND/AIMS—To investigate a poly(2-hydroxyethyl methacrylate) (PHEMA) orbital implant with a spongy anterior hemisphere and a smooth gel posterior hemisphere, by histology correlated with magnetic resonance images.
METHODS—Following enucleation, eight rabbits received PHEMA implants to which the muscles were directly sutured, and underwent gadolinium enhanced magnetic resonance imaging (MRI) from 3 to 52 weeks. After the rabbits were killed, the implants were removed, cut in a plane corresponding to the scan, and processed for light and electron microscopy.
RESULTS—All eight rabbits retained their implant to the end of the study period without complications. The scans demonstrated muscle attachment to the anterior half of the implant, and enhancement was seen on injection of gadolinium chelate. Histology confirmed muscle attachment, and cellular and vascular ingrowth. Over time, a transformation from reactive inflammatory to relatively non-vascular scar tissue was seen within the implant. Calcium deposits in one implant were detected by imaging and histology.
CONCLUSION—The implants are readily visualised on MRI. Muscle attachment and fibrovascular ingrowth into the anterior hemisphere are seen, while encapsulation of the posterior hemisphere is minimal. Histological findings confirm the progress of the healing response, with initial inflammation and marked vascularisation, developing later into quiescent scar tissue predominantly of fibroblasts.

PMCID: PMC1723032  PMID: 10216066
8.  Biofouling of Polymer Hydrogel Materials and its Effect on Diffusion and Enzyme-Based Luminescent Glucose Sensor Functional Characteristics 
Continuous glucose monitoring is crucial to developing a successful artificial pancreas. However, biofouling and host response make in vivo sensor performance difficult to predict. We investigated changes in glucose diffusivity and sensor response of optical enzymatic glucose sensors due to biological exposure.
Three hydrogel materials, poly(2-hydroxyethyl methacrylate) (pHEMA), poly(acrylamide) (pAM), and poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (p(HEMA-co-AM)), were tested for glucose diffusivity before and after exposure to serum or implantation in rats for 1 month. Luminescent sensors based on these materials were measured to compare the response to glucose before and after serum exposure.
Glucose diffusivity through the pHEMA [(8.1 ± 0.38) × 10-8 cm2/s] slabs was much lower than diffusivity through pAM [(2.7 ± 0.15) × 10-6 cm2/s] and p(HEMA-co-AM) [(2.5 ± 0.08) × 10-6]. As expected from these differences, sensor response was highly dependent on material type. The pHEMA sensors had a maximum sensitivity of 2.5%/(mg/dl) and an analytical range of 4.2–356 mg/dl, while the p(HEMA-co-AM) sensors had a higher sensitivity [14.9%/(mg/dl)] and a narrower analytical range (17.6–70.5 mg/dl). After serum exposure, the pHEMA sensors were unaffected, whereas the p(HEMA-co-AM) sensors exhibited significantly decreased sensitivity and increased analytical range.
Decreases in glucose diffusivity in the polymers resulting from in vitro serum exposure and residence in vivo were shown to be similar, suggesting that serum incubation was a reasonable approximation of in vivo fouling. While biofouling is expected to affect the response of flux-based sensors, we have shown that this depended on the type of sensor and matrix used. Therefore, proper design and materials selection may minimize response alterations occurring upon implantation.
PMCID: PMC3570866  PMID: 23294771
biofouling; biomaterials; biosensing; enzymes; luminescence; transport
9.  Designing PolyHEMA Substrates that Mimic the Viscoelastic Response of Soft Tissue 
Journal of biomechanics  2011;44(8):1491-1498.
Matching the mechanical properties of a biomaterial to soft tissue is often overlooked despite the fact that it’s well known that cells respond to and are capable of changing their mechanical environment. In this paper, we used NaCl and alginate beads as porogens to make a series of micro- and macro-porous pHEMA substrates [poly(2-hydroxyethly methacrylate)] and quantified their mechanical behavior under low-magnitude shear loads over physiologically relevant frequencies. Using a stress-controlled rheometer, we performed isothermal (37°C) frequency response experiments between 0.628 and 75.4 rad/s [0.01–12Hz] at 0.1% strain. Both micro- and macro-porous pHEMA substrates were predominately elastic in nature with a narrow range of G′ and G″ values that mimicked the response of human skin. The magnitude of the G′ and G″ values of the macro-porous substrates were designed to closely match human skin. To determine how cell growth might alter their mechanical properties, pHEMA substrates were functionalized and human skin fibroblasts grown on them for fourteen days. As a result of cell growth, the magnitude of G′ and G″ increased at low frequencies while also altering the degree of high frequency dependence, indicating that cellular interactions with the micro-pore infrastructure has a profound effect on the viscoelastic behavior of the substrates. These data could be fit to a mathematical model describing a soft solid. A quantitative understanding of the mechanical behavior of biomaterials in regimes that are physiologically relevant and how these mechanics may change after implantation may aid in the design of new materials.
PMCID: PMC3110658  PMID: 21496821
shear; rheology; viscoelastic; poly (2 hydroxyethyl methacrylate); soft tissue
10.  Degradable poly(2-hydroxyethyl methacrylate)-co-polycaprolactone Hydrogels for Tissue Engineering Scaffolds 
Biomacromolecules  2008;9(12):3370-3377.
Biodegradable poly(2-hydroxyethyl methacrylate) hydrogels for engineered tissue constructs were developed using atom transfer radical polymerization (ATRP), a degradable crosslinker and a macroinitiator. Hydrogels are appropriate materials for tissue engineering scaffolds due to their tissue-like mechanical compliance and mass transfer properties. However, many hydrogels that have seen wide application in medicine are not biodegradable or cannot be easily cleared from the body. Poly(2-hydroxyethyl methacrylate) (pHEMA) was selected for the scaffold material due to its reasonable mechanical strength, elasticity, long history of successful use in medicine and because it can be easily fabricated into numerous configurations. pHEMA was studied at various molecular weights between 2 kDa and 50 kDa. The molecular weight range suitable for renal clearance was an important factor in the experimental design. The fabricated hydrogels contain oligomeric blocks of polycaprolactone (PCL), a hydrolytically and enzymatically degradable polymer, as a crosslinking agent. In addition a degradable macroinitiator also containing oligomeric PCL was used to initiate the ATRP. The chain length, crosslink density, and polymerization solvent were found to greatly affect the mechanical properties of the pHEMA hydrogels. Degradation of the pHEMA hydrogels was characterized using 0.007 M NaOH, lipase solutions and phosphate buffered saline. Mass loss, swelling ratio and tensile modulus were evaluated. Degradation products from the sodium hydroxide were measured using gel permeation chromatography (GPC) to verify the polymer lengths and polydispersity. Erosion was only observed in the sodium hydroxide and lipase solutions. However, swelling ratio and tensile modulus indicate bulk degradation in all PCL containing samples. Degradable hydrogels in enzymatic solutions showed 30% mass loss in 16 weeks. Initial cell toxicity studies indicate no adverse cellular response to the hydrogels or their degradation products. These hydrogels have appropriate mechanical properties, a tunable degradation rate, and are composed of materials currently in FDA approved devices. Thus the degradable pHEMA developed in this study has considerable potential as a scaffold for tissue engineering in cardiac and other applications.
PMCID: PMC2650022  PMID: 19061434
PolyHEMA; Polycaprolactone; ATRP; Cardiac Tissue Engineering; Degradation
11.  Triazacryptand-Based Fluorescent Sensors for Extracellular and Intracellular K+ Sensing 
Biomaterials  2011;32(33):8574-8583.
A 4-amino-naphthalimide derived fluorophore with a triazacryptand moiety ligand was synthesized as a potassium ion (K+) sensor (KS1). This sensor is a monomer possessing a polymerizable vinyl group. By taking advantage of the polymerizable characteristics of the vinyl group, KS1 was polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form K+-sensing films for extracellular sensing. The sensitivity of the films to potassium ions can be further tuned through the adjustment of the HEMA and AM weight ratios as well as introduction of positive or negative charge-containing segments. KS1 and its poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (PHEMA-co-PAM) thin films show high selectivity for K+ over competing sodium ions (Na+) at physiological concentrations. Extracellular sensing was demonstrated using a KS1-conjugated PHEMA-co-PAM thin film to measure the K+ efflux of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) stimulated by lysozyme. Meanwhile, KS1 itself permeates human glioblastoma U87MG and human esophagus premalignant CP-A cell lines. KS1 was used to monitor K+ efflux stimulated by adenosine-5'-triphosphate (ATP), amphotericin, and a mixture of nigericin, bumetanide and ouabain, demonstrating application of this material as an intracellular potassium ion sensor.
PMCID: PMC3177004  PMID: 21855134
Potassium ion sensor; Amino-naphthalimide; Intracellular sensing; Extracellular sensing; Fluorescent probe
12.  Determination of Ammonium Ion Using a Reagentless Amperometric Biosensor Based on Immobilized Alanine Dehydrogenase 
Sensors (Basel, Switzerland)  2011;11(10):9344-9360.
The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of ammonium ion (NH4+) usually requires the addition of pyruvate substrate and reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the reaction. This addition of reagents is inconvenient when an enzyme biosensor based on AlaDH is used. To resolve the problem, a novel reagentless amperometric biosensor using a stacked methacrylic membrane system coated onto a screen-printed carbon paste electrode (SPE) for NH4+ ion determination is described. A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2-hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH) enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate, NH4+ was consumed in the process and thus the signal from the electrocatalytic oxidation of NADH at an applied potential of +0.55 V was proportional to the NH4+ ion concentration under optimal conditions. The stacked methacrylate membranes responded rapidly and linearly to changes in NH4+ ion concentrations between 10–100 mM, with a detection limit of 0.18 mM NH4+ ion. The reproducibility of the amperometrical NH4+ biosensor yielded low relative standard deviations between 1.4–4.9%. The stacked membrane biosensor has been successfully applied to the determination of NH4+ ion in spiked river water samples without pretreatment. A good correlation was found between the analytical results for NH4+ obtained from the biosensor and the Nessler spectrophotometric method.
PMCID: PMC3231275  PMID: 22163699
biosensor; ammonium ion; reduced nicotinamide adenine dinucleotide; poly(2-hydroxyethyl methacrylate); alanine dehydrogenase
13.  Sustained release of antibiotic from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery 
Biomaterials  2009;30(29):5675.
Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin™ antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.
PMCID: PMC2820401  PMID: 19631376
Drug delivery; Hydrogel; Intraocular lenses; Endophthalmitis; Infections
14.  Proliferation of Myoblast Skeletal Cells on Three-Dimensional Supermacroporous Cryogels 
Cardiac and skeletal muscle tissue engineering provides a smart approach to overcome problems associated with organ transplantation and cardiac tissue and also lays a platform for superior alternative approaches in muscle regeneration. The aim of the study was to demonstrate cryogel scaffold potential in the field of skeletal muscle and cardiac tissue engineering. Poly-hydroxyethyl methacrylate (pHEMA)-gelatin cryogel scaffold was synthesized using cryogelation technique and such a designed material is being reported first time. Rheology study of the pHEMA-gelatin (HG) suggested that the cryogel scaffolds were stable at different temperatures and phase angle remained constant in both dry and wet state. HG cryogel was able to bear increased stress without leading to deformation. Monitoring the hydration of HG scaffold showed shift from a stiff to a more pliable material and upon continuing hydration, shear modulus remained constant with no further change observed. However, the change in phase angle <0.24º indicates a gradual increase in stiffness of the material over time. Scaffold synthesised using such polymer combinations gave cells a native environment for proliferation and surface stiffness have shown to help in differentiation of the cells. Myoskeletal cell lines were cultured on these scaffolds to check the biocompatibility and cell proliferation. Alamar blue assay performed over a period of 3 weeks analysed the metabolic activity of cells which showed more than 60% increase in the total cellular activity. DNA content of cells was found to be directly related to number of cells present at a given time point and this was found to have increased by more than 50% in 3 weeks. Since in 3-D scaffold the surface area is more in comparison to 2-D, hence better cell proliferation is observed. Hoechst and DAPI staining showed tubular structure and alignment of the cells during formation of the tubules shows promising cellular response to the cryogel matrix. The mechanical strength, stiffness and elastic measurements of the scaffold indicated potential application of these materials for skeletal and cardiac tissue engineering.
PMCID: PMC2899455  PMID: 20617130
Cryogel; pHEMA-gelatin; C2C12 myocardial cells; Skeletal tissue engineering; Rheology; Myotubes
15.  Ultrasonic synthetic technique to manufacture a pHEMA nanopolymeric-based vaccine against the H6N2 avian influenza virus: a preliminary investigation 
This preliminary study investigated the use of poly (2-hydroxyethyl methacrylate) (pHEMA) nanoparticles for the delivery of the deoxyribonucleic acid (DNA) vaccine pCAG-HAk, which expresses the full length hemagglutinin (HA) gene of the avian influenza A/Eurasian coot/Western Australian/2727/1979 (H6N2) virus with a Kozak sequence which is in the form of a pCAGGS vector. The loaded and unloaded nanoparticles were characterized using field-emission scanning electron microscopy. Further characterizations of the nanoparticles were made using atomic force microscopy and dynamic light scattering, which was used to investigate particle size distributions. This preliminary study suggests that using 100 μg of pHEMA nanoparticles as a nanocarrier/adjuvant produced a reduction in virus shedding and improved the immune response to the DNA vaccine pCAG-HAk.
PMCID: PMC3215157  PMID: 22114480
nanoparticles; ultrasound; deoxyribonucleic acid; plasmid; bird flu; pandemic
16.  Elastomeric high-mineral content hydrogel-hydroxyapatite composites for orthopedic applications 
The design of synthetic bone grafts that mimic the structure and composition of bone and possess good surgical handling characteristics remains a major challenge. We report the development of poly(2-hydroxyethyl methacrylate) (pHEMA)-hydroxyapatite (HA) composites termed “FlexBone” that possess osteoconductive mineral content approximating that of human bone yet exhibit elastomeric properties enabling the press-fitting into a defect site. The approach involves crosslinking pHEMA hydrogel in the presence of HA using viscous ethylene glycol as a solvent. The composites exhibit excellent structural integration between the apatite mineral component and the hydroxylated hydrogel matrix. The stiffness of the composite and the ability to withstand compressive stress correlate with the microstructure and content of the mineral component. The incorporation of porous aggregates of HA nanocrystals rather than compact micrometer-sized calcined HA effectively improved the resistance of the composite to crack propagation under compression. Freeze-dried FlexBone containing 50 wt % porous HA nanocrystals could withstand hundreds-of-megapascals compressive stress and >80% compressive strain without exhibiting brittle fractures. Upon equilibration with water, FlexBone retained good structural integration and withstood repetitive moderate (megapascals) compressive stress at body temperature. When subcutaneously implanted in rats, FlexBone supported osteoblastic differentiation of the bone marrow stromal cells pre-seeded on FlexBone. Taken together, the combination of high osteoconductive mineral content, excellent organic-inorganic structural integration, elasticity, and the ability to support osteoblastic differentiation in vivo makes FlexBone a promising candidate for orthopedic applications.
PMCID: PMC2745393  PMID: 18546185
hydrogel; hydroxyapatite; elastomeric composites; osteoblastic differentiation; bone marrow stromal cells
17.  Development of a Portable Taste Sensor with a Lipid/Polymer Membrane 
Sensors (Basel, Switzerland)  2013;13(1):1076-1084.
We have developed a new portable taste sensor with a lipid/polymer membrane and conducted experiments to evaluate the sensor's performance. The fabricated sensor consists of a taste sensor chip (40 mm × 26 mm × 2.2 mm) with working and reference electrodes and a portable sensor device (80 mm × 25 mm × 20 mm). The working electrode consists of a taste-sensing site comprising a poly(hydroxyethyl)methacrylate (pHEMA) hydrogel layer with KCl as the electrolyte layer and a lipid/polymer membrane as the taste sensing element. The reference electrode comprises a polyvinyl chloride (PVC) membrane layer with a small hole and a pHEMA layer with KCl. The whole device is the size of a USB memory stick, making it suitable for portable use. The sensor's response to tannic acid as the standard astringency substance showed good accuracy and reproducibility, and was comparable with the performance of a commercially available taste sensing system. Thus, it is possible for this sensor to be used for in-field evaluations and it can make a significant contribution to the food industry, as well as in various fields of research.
PMCID: PMC3574722  PMID: 23325168
taste sensor; lipid/polymer membrane; portable sensor; in-field evaluation
18.  Sensitization Potential of Dental Resins: 2-Hydroxyethyl Methacrylate and Its Water-Soluble Oligomers Have Immunostimulatory Effects 
PLoS ONE  2013;8(11):e82540.
The immunostimulatory effects of the representative dental resin monomer 2-hydroxyethyl methacrylate (HEMA), a HEMA derivative that does not contain a double bond (2-hydroxyethyl isobutyrate, HEIB), and polymerized water-soluble oligomers of HEMA (PHEMA) were investigated. It is known that expression levels of either or both of CD54 and CD86 in THP-1 cells are increased by exposure to sensitizing substances. In this study, the expression levels of CD54 and CD86, the production of reactive oxygen species (ROS), and the viability of the cells were measured after 24 h of incubation with these materials at different concentrations. The concentrations of the materials that induced the expression of both CD54 and CD86 were low in the following order: NiSO4, HEMA, and methyl methacrylate (MMA). These results indicate that these dental resin monomers have lower sensitizing potentials than NiSO4. Although HEIB, which lacks a double bond, resulted in negligible ROS production and reduced cytotoxicity than HEMA, it induced the expression of CD54 and CD86. Comparison of the results for HEMA and HEIB indicates that dental resin monomer-induced sensitization may be related not only to the oxidative stress related to the methacryloyl group but also to the structures of these compounds. Of particular interest is the result that a water-soluble PHEMA oligomer with a relatively high-molecular weight also exhibited negligible cytotoxicity, whereas the expression level of CD54 increased after exposure to PHEMA at a high concentration. This result serves as a warning that polymerized substances also have the potential to induce sensitization. This study provides insight into the nature of allergic responses to dental resin materials in clinical use and may facilitate the development of more biocompatible restorative materials in the future.
PMCID: PMC3843711  PMID: 24312427
19.  Ferritin immobilization on patterned poly(2-hydroxyethyl methacrylate) brushes on silicon surfaces from colloid system 
Colloid and Polymer Science  2011;289(4):433-445.
In this paper, we describe a graft polymerization/solvent immersion method for generating poly(2-hydroxyethyl methacrylate) (PHEMA) brushes in various patterns. We used a novel fabrication process, involving very-large-scale integration and oxygen plasma treatment, to generate well-defined patterns of polymerized PHEMA on patterned Si(100) surfaces. We observed brush- and mushroom-like regions for the PHEMA brushes, with various pattern resolutions, after immersing wafers presenting lines of these polymers in MeOH and n-hexane, respectively. The interaction between PHEMA and ferritin protein sheaths in MeOH and n-hexane (good and poor solvent for PHEMA, respectively) was used to capture and release ferritins from fluidic system. The “tentacles” behaver for PHEMA brushes was found through various solvents in fluidic system. Using high-resolution scanning electron microscopy, we observed patterned ferritin Fe cores on the Si surface after pyrolysis of the patterned PHEMA brushes and ferritin protein sheaths, which verify the “tentacles” behaver for PHEMA brushes.
PMCID: PMC3040805  PMID: 21461041
PHEMA brush; Nanolithography; Ferritin
20.  2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation 
Molecular Biology Reports  2011;39(2):1561-1574.
HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action.
PMCID: PMC3249584  PMID: 21617943
Dental restorative materials; 2-hydroxylmethyl methacrylate; HEMA; Degradation; DNA damage; Cell cycle
21.  Correlations between Chemical Compositions and Retention Times of Methacrylate Random Copolymers Using LC-ESI-MS 
Mass Spectrometry  2012;1(2):A0012.
Correlations between chemical compositions and chromatographic retention times (Rt) of methacrylate random copolymers were studied by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). Twenty-six different polymers including homopolymers of poly(methyl methacrylate) (PMMA), poly(tert-butyl methacrylate) (PTBMA) and poly(2-hydroxyethyl methacrylate) (PHEMA), and their random copolymers of P(MMA-TBMA) and P(MMA-HEMA) with known chemical compositions were studied. The results indicate that there is close correlations between the chemical compositions of the random copolymers and their Rt of the C8 column in the mass spectral ranges of m/z 1,800–2,000. The LC-ESI-MS analysis showed molecular weights of the copolymers distribute in the mass range of ca. 500–20,000, and the structures of polymer terminals and their monomer units can be identified.
PMCID: PMC3775824  PMID: 24349913
methacrylate random copolymers; LC-MS; correlations between chemical compositions and retention times
22.  Real time in vitro studies of doxorubicin release from PHEMA nanoparticles 
Many anticancer agents have poor water solubility and therefore the development of novel delivery systems for such molecules has received significant attention. Nanocarriers show great potential in delivering therapeutic agents into the targeted organs or cells and have recently emerged as a promising approach to cancer treatments. The aim of this study was to prepare and use poly-2-hydroxyethyl methacrylate (PHEMA) nanoparticles for the controlled release of the anticancer drug doxorubicin.
PHEMA nanoparticles have been synthesized and characterized using FTIR and scanning electron microscopy (SEM), particle size analysis and surface charge measurements. We also studied the effects of various parameters such as percent loading of drugs, chemical architecture of the nanocarriers, pH, temperature and nature of the release media on the release profiles of the drug. The chemical stability of doxorubicin in PBS was assessed at a range of pH.
Suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) results in the formation of swellable nanoparticles of defined composition. PHEMA nanoparticles can potentially be used for the controlled release of the anticancer drug doxorubicin.
PMCID: PMC2770983  PMID: 19843333
23.  Polymer Brush-Modified Magnetic Nanoparticles for His-Tagged Protein Purification 
Growth of poly(2-hydroxyethyl methacrylate) brushes on magnetic nanoparticles and subsequent brush functionalization with nitrilotriacetate-Ni2+ yield magnetic beads that selectively capture polyhistidine-tagged (His-tagged) protein directly from cell extracts. Transmission electron microscopy, FT-IR spectroscopy, thermogravimetric analysis, and magnetization measurements confirm and quantify the formation of the brushes on magnetic particles, and multilayer protein adsorption to these brushes results in binding capacities (220 mg BSA/g of beads and 245 mg His-tagged Ubiquitin/g of beads) that are an order of magnitude greater than those of commercial magnetic beads. Moreover, the functionalized beads selectively capture His-tagged protein within 5 min. The high binding capacity and protein purity along with efficient protein capture in a short incubation time make brush-modified particles attractive for purification of recombinant proteins.
PMCID: PMC3153590  PMID: 21338107
polymer brush; magnetic beads; His-tagged proteins
24.  Integrated Capture, Concentration, PCR, and Capillary Electrophoretic Analysis of Pathogens on a Chip 
Analytical chemistry  2009;81(9):3523-3528.
A lab-on-a-chip system for pathogen detection is presented that integrates cell preconcentration, purification, PCR, and capillary electrophoretic (CE) analysis. The microdevice is comprised of micropumps and valves, a cell capture structure, a 100 nL PCR reactor, and a 5-cm long CE column for amplicon separation. Sample volumes ranging from 10 to 100 μL are introduced and driven through a fluidized bed of magnetically constrained immunomagnetic beads where the target cells are captured. After cell capture, beads are transferred using the on-chip pumps to the PCR reactor for DNA amplification. The resulting PCR products are electrophoretically injected onto the CE column for separation and detection of E. coli K12 and E. coli O157 targets. A detection limit of 0.2 cfu/μL is achieved using the E. coli O157 target and an input volume of 50 μL. Finally, the sensitive detection of E. coli O157 in the presence of K12 at a ratio of 1:1000 illustrates the capability of our system to identify target cells in a high commensal background. This cell capture-PCR-CE microsystem is a significant advance in the development of rapid, sensitive, and specific lab-on-a-chip devices for pathogen detection.
PMCID: PMC2684796  PMID: 19341275
lab-on-a-chip; pathogen detection; cell capture; PCR; capillary electrophoresis
25.  Time-dependent mechanical characterization of poly(2-hydroxyethyl methacrylate) hydrogels using nanoindentation and unconfined compression 
Journal of materials research  2008;23(5):1472-1481.
Hydrogels pose unique challenges to nanoindentation including sample preparation, control of experimental parameters, and limitations imposed by mechanical testing instruments and data analysis originally intended for harder materials. The artifacts that occur during nanoindentation of hydrated samples have been described, but the material properties obtained from hydrated nanoindentation have not yet been related to the material properties obtained from macroscale testing. To evaluate the best method for correlating results from microscale and macroscale tests of soft materials, nanoindentation and unconfined compression stress-relaxation tests were performed on poly-2-hydroxyethyl methacrylate (pHEMA) hydrogels with a range of cross-linker concentrations. The nanoindentation data were analyzed with the Oliver–Pharr elastic model and the Maxwell–Wiechert (j = 2) viscoelastic model. The unconfined compression data were analyzed with the Maxwell–Wiechert model. This viscoelastic model provided an excellent fit for the stress-relaxation curves from both tests. The time constants from nanoindentation and unconfined compression were significantly different, and we propose that these differences are due to differences in equilibration time between the microscale and macroscale experiments and in sample geometry. The Maxwell–Wiechert equilibrium modulus provided the best agreement between nanoindentation and unconfined compression. Also, both nanoindentation analyses showed an increase in modulus with each increasing cross-linker concentration, validating that nanoindentation can discriminate between similar, low-modulus, hydrated samples.
PMCID: PMC2600455  PMID: 19081812

Results 1-25 (129018)