PHEMA Hydrogels Research Articles

In vitro–ex vivo correlations between a cell-laden hydrogel and mucosal tissue for screening composite delivery systems

Composite delivery systems where drugs are electrospun in different layers and vary the drug stacking-order are posited to affect bioavailability. We evaluated how the formulation characteristics of both burst- and sustained-release electrospun fibers containing three physicochemically diverse drugs: dapivirine (DPV), maraviroc (MVC) and tenofovir (TFV) affect in vitro and ex vivo release. We developed a poly(hydroxyethyl methacrylate) (pHEMA) hydrogel release platform for the rapid, inexpensive in vitro evaluation of burst- and sustained-release topical or dermal drug delivery systems with varying microarchitecture. We investigated properties of the hydrogel that could recapitulate ex vivo release into nonhuman primate vaginal tissue. Using a dimethyl sulfoxide extraction protocol and high-performance liquid chromatography analysis, we achieved >93% recovery from the hydrogels and >88% recovery from tissue explants for all three drugs. We found that DPV loading, but not stacking order (layers of fiber containing a single drug) or microarchitecture (layers with isolated drug compared to all drugs in the same layer) impacted the burst release in vitro and ex vivo. Our burst-release formulations showed a correlation for DPV accumulation between the hydrogel and tissue (R2= 0.80), but the correlation was not significant for MVC or TFV. For the sustained-release formulations, the PLGA/PCL content did not affect TFV release in vitro or ex vivo. Incorporation of cells into the hydrogel matrix improved the correlation between hydrogel and tissue explant release for TFV. We expect that this hydrogel-tissue mimic may be a promising preclinical model to evaluate topical or transdermal drug delivery systems with complex microarchitectures.

One-step synthesis of PHEMA hydrogel films capable of generating highly ordered wrinkling patterns

Poly(2-hydroxyethyl methacrylate) (PHEMA) films with gradient crosslinking density are the only hydrogel films capable of generating regular wrinkling patterns upon swelling, however, they were synthesized via a complicated two-stage photopolymerization. In an effort to develop a simple synthesis method, we found that one-step UV-curing of HEMA liquid always results in films with corrugated surface, which is a common issue when curing liquid prepolymers. We further found that the introduction of a physical network in the prepolymer solution could prevent the surface from corrugating during UV curing. For this purpose, linear PHEMA was added into the prepolymer solutions, and PHEMA films with a smooth surface were successfully synthesized by a simple one-step UV curing. The resulting films generate various swelling-induced wrinkling patterns, including random worms, peanuts and long-range ordered hexagons, depending on the contents of crosslinker and linear PHEMA in the prepolymer solution. Particularly, large area, highly ordered, honeycomb-like wrinkling patterns were obtained from films with proper content of crosslinker and linear PHEMA. These regular patterns are expected to find applications such as the fabrication of uniform multicellular spheroids.

Preparatıon and Application of Biocompatible Carrier Implant to be Used in the Controlled Acquisition of Digoxin

In this study, a persistent system is aimed to be established which contributes to slow basal digoxin release in the treatment of cardiac failure. Poly(2-hydroxyethyl-metacrylate-methylmetacrylate) (p(HEMA-MMA) copolymer that can swell by taking on water is prepared in cylindirical form by UV photopolymerization method for the controlled-release of digoxin and effective hydrogel implant formulation. A batch of p(HEMA-MMA) composition is prepared in different monomer ratios. Biocompatibility is improved by adding PEO, PEG and serum albumine to the structures of p(HEMA-MMA), respectively. Scanning electron microscope (SEM) studies are carried out for the surface structure of the prepared carrier implant material and differential scanning calorimetry (DSC) studies for the thermal stability analysis. Swelling behaviors are investigated by transferring solvent molecules to the hydrogels. Digoxin release kinetics are evaluated by applying three different accumulative digoxin doses (100, 250 and 500 U/mL) in the persistent flow release system containing physiological phosphate. Power law, level-zero, and Higuchi model equations are utilized so as to evaluate the release mechanism of digoxin. The most suitable results are acquired from the composition whose HEMA:MMA monomer ratio is 1:0.5 (v/v) in drug accumulation and release studies. It is observed from the SEM image that the carrier implant in the structure of the acquired hydrogel has a smooth surface. According to DSC results, it is seen that thermal stability decreases in the event that MMA comonomer is added to the structure of the pHEMA hydrogel. Balance water amount within the physiological phosphate buffer of the p(HEMA-MMA) copolymer is observed to be less than the pHEMA. Digoxin release loaded to carrier implants by different ratios takes a long-term period as expected. It is decided that the formulation established in the study can be successfully applied for the basal digoxin level over four weeks in the treatment of chronic cardiac failure.

A Composite Material Based on Poly(2-hydroxyethyl methacrylate) with Hydroxyapatite Microparticle Inclusions

An organo-mineral composite bone-grafting material was developed and tested. The composite material is based on synthetic hydroxyapatite (HAP) (30-60 wt%) integrated into the matrix of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel. The composite was shown to have a homogeneous and isotropic microstructure, mechanical strength of ~11 MPa, high degree of water absorption reaching 34%, and elastomeric properties under physio-logical conditions (strain at failure is 57%).

Hydrogels of poly(2‐hydroxyethyl methacrylate) reinforced with nanocrystalline cellulose as candidates for biomaterials

Nanocomposite hydrogels were prepared based on crosslinked poly(2‐hydroxyethyl methacrylate) (PHEMA) as polymer matrix and nanocrystalline cellulose fibers (NCC) as nanomaterial filler. NCC fibers were obtained by acid hydrolysis of cotton and pristine PHEMA and PHEMA nanocomposite hydrogels were synthesized by photopolymerization. Physicochemical, thermal, and mechanical properties of pristine and nanocomposite hydrogels were evaluated by differential scanning calorimetry, thermogravimetric analysis, mechanical tests by submersion compression, and measurements of swelling at equilibrium. Results showed that the compressive modulus of PHEMA hydrogels increased significantly with addition of only 1wt% of NCC fibers. Furthermore, PHEMA nanocomposite hydrogels exhibit higher water swelling degree and are thermally more stable than pristine PHEMA hydrogels. POLYM. COMPOS., 39:E278–E285, 2018. © 2016 Society of Plastics Engineers

High refractive index TiO2-PHEMA hydrogel for ophthalmological applications

A facile route for the synthesis of PHEMA hydrogel incorporating anatase nanoparticles is presented. The hydrogel features a refractive index of 1.527 and high transparency throughout the visual spectral range. Saturn rings have been machined in order to investigate the workability of the material and its potential applicability as intraocular lens implant. The resulting lenses feature high surface quality, foldability, and shape memory which makes them suitable for implantation via extracapsular cataract extraction.

Micropatterned Hydrogel Surface with High-Aspect-Ratio Features for Cell Guidance and Tissue Growth.

Surface topography has been introduced as a new tool to coordinate cell selection, growth, morphology, and differentiation. The materials explored so far for making such structural surfaces are mostly rigid and impermeable. Hydrogel, on the other hand, was proved a better synthetic media for cell culture because of its biocompatibility, softness, and high permeability. Herein, we fabricated a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel substrate with high-aspect-ratio surface microfeatures. Such structural surface could effectively guide the orientation and shape of human mesenchymal stem cells (HMSCs). Notably, on the flat hydrogel surface, cells rounded up, whereas on the microplate patterned hydrogel surface, cells elongated and aligned along the direction parallel to the plates. The microplates were 2 μm thick, 20 μm tall, and 10-50 μm wide. The interplate spacing was 5-15 μm, and the intercolumn spacing was 5 μm. The elongation of cell body was more pronounced on the patterns with narrower interplate spacing and wider plates. The cells behaved like soft solid. The competition between surface energy and elastic energy defined the shape of the cells on the structured surfaces. The soft permeable hydrogel scaffold with surface structures was also demonstrated as being viable for long-term cell culture, and could be used to generate interconnected tissues with finely tuned cell morphology and alignment across a few centimeter sizes.

PHEMA Encapsulated PEDOT-PSS-CNT Microsphere Microelectrodes for Recording Single Unit Activity in the Brain.

The long-term reliability of neural interfaces and stability of high-quality recordings are still unsolved issues in neuroscience research. High surface area PEDOT-PSS-CNT composites are able to greatly improve the performance of recording and stimulation for traditional intracortical metal microelectrodes by decreasing their impedance and increasing their charge transfer capability. This enhancement significantly reduces the size of the implantable device though preserving excellent electrical performances. On the other hand, the presence of nanomaterials often rises concerns regarding possible health hazards, especially when considering a clinical application of the devices. For this reason, we decided to explore the problem from a new perspective by designing and testing an innovative device based on nanostructured microspheres grown on a thin tether, integrating PEDOT-PSS-CNT nanocomposites with a soft synthetic permanent biocompatible hydrogel. The pHEMA hydrogel preserves the electrochemical performance and high quality recording ability of PEDOT-PSS-CNT coated devices, reduces the mechanical mismatch between soft brain tissue and stiff devices and also avoids direct contact between the neural tissue and the nanocomposite, by acting as a biocompatible protective barrier against potential nanomaterial detachment. Moreover, the spherical shape of the electrode together with the surface area increase provided by the nanocomposite deposited on it, maximize the electrical contact and may improve recording stability over time. These results have a good potential to contribute to fulfill the grand challenge of obtaining stable neural interfaces for long-term applications.

Zwitterionic hydrogels promote skin wound healing.

Skin traumas are among the most common health problems in the world, and are routinely treated with wound dressings such as bandages and gauze. Traditional dressings are typically made of dry cotton, which tends to adhere to the wound, causing scab formation and bacterial infections. Ideally, a dressing should accelerate wound healing while avoiding any side effects or complications. Recent studies have found that wet dressings, especially hydrogels, can provide a moist environment for wounds that mimics the in vivo environment, thus facilitating debridement of necrotic tissue, enhancing tissue regeneration, and avoiding scab formation. Zwitterionic hydrogels exhibit strong hydration, are biomimetic in nature, and show excellent anti-fouling properties; their resulting high water content, excellent biocompatibility, and negligible interactions with proteins and cells make them ideal wet wound dressings. In this work, we demonstrated that zwitterionic hydrogels, especially poly-carboxybetaine (PCB) hydrogels, can efficiently promote skin wound healing. Skin wounds treated with zwitterionic hydrogels healed significantly better than those treated with PHEMA hydrogels and the commercial product DuoDerm. Moreover, these zwitterionic hydrogels can be easily coated on cotton gauze or bandage pads for easy handling and application. The findings in this work hold great promise for the development of next-generation wound dressings to improve healthcare.

PHEMA hydrogels with pendant triazinyl-β-cyclodextrin as an efficient and recyclable reservoir for loading and release of plant-based mosquito repellents: a new aqueous mosquito repellent formulation

Poly(2-hydroxyethyl methacrylate) hydrogels with pendant β-cyclodextrins as an efficient and recyclable reservoir for loading and release of plant-based mosquito repellents.

3D chemical characterization of frozen hydrated hydrogels using ToF-SIMS with argon cluster sputter depth profiling.

Hydrogels have been used extensively in bioengineering as artificial cell culture supports. Investigation of the interrelationship between cellular response to the hydrogel and its chemistry ideally requires methods that allow characterization without labels and can map species in three-dimensional to follow biomolecules adsorbed to, and absorbed into, the open structure before and during culture. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has the potential to be utilized for through thickness characterization of hydrogels. The authors have established a simple sample preparation procedure to successfully achieve analysis of frozen hydrated hydrogels using ToF-SIMS without the need for dry glove box entry equipment. They demonstrate this on a poly(2-hydroxyethyl methacrylate) (pHEMA) film where a model protein (lysozyme) is incorporated using two methods to demonstrate how protein distribution can be determined. A comparison of lysozyme incorporation is made between the situation where the protein is present in a polymer dip coating solution and where lysozyme is in an aqueous medium in which the film is incubated. It is shown that protonated water clusters H(H2O)n (+) where n = 5-11 that are indicative of ice are detected through the entire thickness of the pHEMA. The lysozyme distribution through the pHEMA hydrogel films can be determined using the intensity of a characteristic amino acid secondary ion fragment.

Characterization of Inflammatory Cell Response to Implanted Porous P‐HEMA in the Dermis Vs Subcutaneous Tissue

We evaluated macrophage polarization and vascularization adjacent to porous implants. Porous poly-2-hydroxyethylmethacrylate (pHEMA) hydrogel ribbons (0.7mm x 0.5mm x 5mm) with 80 µm pores were injected into pig dermis and subcutis. Macrophage and microvascular densities at 1 week and 1 month were measured via immunohistochemistry; CD68 (all macrophages), CD80 (M1 pro-inflammatory macrophages), CD163 (M2 pro-healing macrophages) and CD31 (endothelium). M1 density after 1 week was lower in dermis vs subcutis (213±35 M1 cells/mm2 vs 391±43 M1 cells/mm2, p<.01). After 1 month M1's decreased in subcutis and dermis. There were no significant difference in M1 density (207±22 M1 cells/mm2 vs 219±26 M1 cells/mm2, p= 0.74). At 1 week, M2's were greater at the scaffold interface with fat than with dermis (795 ± 23 M2 cells /mm2 vs 515±30 M2s/mm2, p<.01), whereas the M2 density after 1 month was similar for dermis and subcutis (450±28 M2 cells/mm2 vs 464 ± 120 M2 cells/mm2, p= 0.91). After 1 week, pHEMA next to fat showed faster tissue vascularization within 50 µm of the implant compared to dermal scaffolds (418±36 vs. 211±48 microvessels/mm2; p=0.03). After 1 month, intradermal and subcutis implants showed similar vascularization of tissue and scaffold (218±55 vs. 218±30 mv/mm2 in tissue; p=1.00; and 286±37 vs. 290±37 mv/mm2 in pHEMA; p=0.95). M2's were higher at the implant-tissue interface compared to M1's. Porous biomaterials yield faster neovascularization and higher pro-healing macrophage density.

Rapid isoelectric point determination in a miniaturized preparative separation using jet-dispensed optical pH sensors and micro free-flow electrophoresis.

Herein, the fabrication, characterization, calibration, and application of integrated microfluidic platforms for fast isoelectric point (pI) determinations via free-flow electrophoresis with integrated inkjet-printed fluorescent pH sensor microstructures are presented. These devices allow one to determine the pI of a biomolecule from a sample mixture with moderately good precision and without addition of markers in typically less than 10 s total separation and analysis time. Polyhydroxyethyl methacrylate (pHEMA) hydrogels were covalently coupled with fluorescein and hydroxypyrene trisulfonic acid (HPTS)-based pH probes. These were piezoelectrically jet-dispensed onto acrylate-modified glass as pH sensor microarrays with a diameter of 300-600 μm and thicknesses of 0.4-2.4 μm with high spatial accuracy. Microchip fabrication and integration of these pH sensor arrays was realized by multistep liquid-phase photolithography from oligoethylene glycol precursors resulting in glass-based microfluidic free-flow isoelectric focusing (μFFIEF) chips with integrated pH observation capabilities. The microchips were characterized with regard to pH sensitivity, response times, photo-, and flow stability. Depending on the sensor matrix, they allowed IEF within a pH range of roughly 5.5-10.5 with good sensitivity and fast response times. These microchips were used for FFIEF of small molecule markers and several protein mixtures with simultaneous monitoring of local pH. This allowed the determination of their pI via multispectral imaging of protein and pH sensor fluorescence without addition of external markers. Obtained pI's were generally in good agreement with known data, demonstrating the applicability of the method for pI determination in micropreparative procedures within a time frame of a few seconds only.

AFM in mode Peak Force applied to the study of un-worn contact lenses

Contact lenses (CLs) are of common use and the biocompatibility, topography and mechanical properties of the used materials are of major importance. The objective of this contribution is to apply the AFM in mode Peak Force to obtain surface topography and mechanical characteristics of un-worn CLs of different materials. One material of hydrogel, two of siloxane-hydrogel and one of rigid gas-permeable were used in the study. The results obtained with different materials have been compared, at a nanoscopic level, and the conclusions are diverse. There is no significant influence of the two environments used to measure the characteristics of the CLs, either water or saline solution. The pHEMA hydrogel CL (Polymacon of Soflens) shows the highest values of roughness, adhesion and elastic modulus. The siloxane-hydrogel CL named Asmofilcon A of PremiO presents the lowest values of mean roughness (Ra), root-mean-square roughness (RMS or Rq), adhesion (Adh) and elastic modulus (Ym), meanwhile the siloxane-hydrogel CL named Lotrafilcon B of Air Optix presents the lowest value of skewness (Rsk) and the rigid gas-permeable CL, named RXD, presents the lowest values of kurtosis (Rku) and maximum roughness (Rmax).

Compression Modulus and Equilibrium Swelling Studies of Poly(2-Hydroxyethyl Methacrylate) Hydrogels Formed at Various Polymer Concentrations

The equilibrium swelling degree and modulus of elasticity of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels prepared at various initial monomer concentrations were investigated to understand their characteristic behavior for development as biomaterials. The resulting hydrogels were characterized in terms of the equilibrium swelling and compression stress-strain measurements. The influences of the monomer feed composition on the swelling and the mechanical properties of PHEMA hydrogels were explored. The swelling capacity and network characteristics of the resulting hydrogels were determined through the observation of swelling behavior in water and compression modulus determination both after equilibrium swelling and after their preparation. The equilibrium swelling of PHEMA hydrogels was analyzed by Flory-Rehner theory and the results were combined by the results of elasticity measurements to calculate the molecular characteristics of hydrogels. The mechanical strength of PHEMA hydrogels increased greatly by increasing the gel preparation concentration. The results showed that the gel strength and the mechanical properties of hydrogels can be controlled by changing the polymer concentration and the amount of water used in the gel preparation.

Preparation of novel biodegradable pHEMA hydrogel for a tissue engineering scaffold by microwave-assisted polymerization

ObjectiveTo prepare a novel biodegradable poly(2-hydroxyethylmethacrilate) (pHEMA) hydrogel as tissue engineering scaffold. MethodsThe pHEMA hydrogel was synthesized by microwave-assisted polymerization using 2-hydroxyethyl methacrylate (HEMA) as the raw material, potassium persulfate as the initiator, and PCLX as the cross-linking additive. The hydrogels was characterized with FTIR and NMR spectroscopy. The physical and chemical properties of the prepared hydrogel were evaluated, and its degradation performance was tested. The cytotoxicity of the optimum composite hydrogel was measured by an MTT assay to confirm the feasibility of its use in tissue engineering. ResultsThe optimum conditions under which the hydrogel was prepared by microwave-assisted polymerization are as follows: 1.5 g cross-linking additive, 0.3 g initiator, reaction temperature of 80 °C, and microwave power of 800 W. Degradation studies showed good degradation profiles with 75% in 17 days. Additionally, the hydrogels did not elicit any cytotoxic response in in vitro cytotoxic assays. ConclusionA biodegradable pHEMA hydrogel was successfully prepared by microwave-assisted polymerization, as confirmed from FTIR and NMR results. The hydrogel shows promising applications in tissue engineering, and its healing ability and biocompatibility will be evaluated in detail in the future.

Thermoset composite hydrogels for bone/intervertebral disc interface

We introduce an interesting strategy to develop thermoset composite hydrogels (TCH) integrating calcium deficient hydroxyapatite (CDHA) into poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels. The process consists in two feasible steps: (1) the temperature driven polymerization of hydroxyethylmetacrilate (HEMa) in water or glycerol solution and, (2) the hardening reaction of CDHA triggered by hydrolysis of α-tricalcium phosphates (α-TCP) in NaHPO4 water solution at body temperature. SEM investigation show that final morphology of composite is significantly affected by monomer concentration and used solvents (i.e, water or Glycerol). These results are also in agreement with the characterization of mechanical response under compression performed of different TCH typologies. All the reported results confirm that TCH obtained by thermal curing and hardening reaction may represent a promising bone-like material with interesting properties to mimic the native vertebrae/annulus interface for a non-invasive IVD repair strategies.

Multiwalled CNT‐pHEMA composite conduit for peripheral nerve repair

A nerve conduit is designed to improve peripheral nerve regeneration by providing guidance to the nerve cells. Conductivity of such guides is reported to enhance this process. In the current study, a nerve guide was constructed from poly(2-hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to have a porous structure to facilitate the transportation of the compounds needed for cell nutrition and growth and also for waste removal. We showed that when loaded with relatively high concentrations of mwCNTs (6%, w/w in hydrogels), the pHEMA guide was more conductive and more hydrophobic than pristine pHEMA hydrogel. The mechanical properties of the composites were better when they carried mwCNT. Elastic modulus of 6% mwCNT loaded pHEMA was twofold higher (0.32 ± 0.06 MPa) and similar to that of the soft tissues. Electrical conductivity was significantly improved (11.4-fold) from 7 × 10(-3) Ω(-1).cm(-1) (pHEMA) to 8.0 × 10(-2) Ω(-1).cm(-1) (6% mwCNT loaded pHEMA). On application of electrical potential, the SHSY5Y neuroblastoma cells seeded on mwCNTs carrying pHEMA maintained their viability, whereas those on pure pHEMA could not, indicating that mwCNT helped conduct electricity and make them more suitable as nerve conduits.

SIKVAV-modified highly superporous PHEMA scaffolds with oriented pores for spinal cord injury repair

The architecture and mechanical properties of a scaffold for spinal cord injury treatment must provide tissue integration as well as effective axonal regeneration. Previous work has demonstrated the cell-adhesive and growth-promoting properties of the SIKVAV (Ser-Ile-Lys-Val-Ala-Val)-modified highly superporous poly(2-hydroxethyl methacrylate) (PHEMA) hydrogels. The aim of the current study was to optimize the porosity and mechanical properties of this type of hydrogel in order to develop a suitable scaffold for the repair of spinal cord tissue. Three types of highly superporous PHEMA hydrogels with oriented pores of ~60 µm diameter, porosities of 57-68% and equivalent stiffness characterized by elasticity moduli in the range 3-45 kPa were implanted into a spinal cord hemisection, and their integration into the host tissue, as well as the extent of axonal ingrowth into the scaffold pores, were histologically evaluated. The best tissue response was found with a SIKVAV-modified PHEMA hydrogel with 68% porosity and a moderate modulus of elasticity (27 kPa in the direction along the pores and 3.6 kPa in the perpendicular direction). When implanted into a spinal cord transection, the hydrogel promoted tissue bridging as well as aligned axonal ingrowth. In conclusion, a prospective oriented scaffold architecture of SIKVAV-modified PHEMA hydrogels has been developed for spinal cord injury repair; however, to develop an effective treatment for spinal cord injury, multiple therapeutic approaches are needed.

Development of a Portable Taste Sensor with a Lipid/Polymer Membrane

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.