N-isopropylacrylamide Hydrogel Research Articles

In Vitro Evaluation of a Thermoreversible Hyaluronan-Based Hydrogel Loaded with Cell-Seeded Polyurethane Particles for Nucleus Pulposus Repair

Introduction Thermoreversible hyaluronan (HA) based hydrogels represent a promising carrier for IVD repair because of the mild gel formation allowing for encapsulation of viable cells and biological stimulation of cells by HA.1,2 Additionally, polyurethane (PU) foams can provide elasticity, which is of key importance for the restoration of IVD mechanical function, as the latter experiences repeated loading during the daily human activities. Finally, the addition of relevant cells may promote a faster restoration of the IVD function. Therefore, the aim of this study was to compare the single and combined effect of PU particles and HA hydrogel on the proliferation and differentiation of human IVD and mesenchymal stem cells. Materials and Methods Human bone marrow stromal cells (hMSCs) or human disk cells (hIVD cells) (P2-P4) were seeded on PU particles; after 12 hours, the seeded particles were suspended in either a 12% w/v thermoreversible hyaluronan-poly(N-isopropylacrylamide) hydrogel (HA-pNIPAM)2 or in a fibrinogen/thrombin solution.3 Each sample contained 50 µL hydrogel, 2.5 mg PU particles, and 2.5 × 105 cells. Controls included hMSC (or hIVD cells) seeded HA-pNIPAM, hMSC (or hIVD cells) seeded fibrin, and hMSC (or hIVD cells) seeded PU. After gelling for 1 hour at 37°C, samples were cultured in chondrogenic medium (DMEM high glucose, 1% ITS, 130 µM ascorbic acid, 100 nM dexamethasone and 10 ng/mL TGF-β1) for one week and analyzed for DNA (by Picogreen), sulfated glycosaminoglycan (GAG) (by 1,9 dimethylmethylene blue), mRNA expression, and histology (toluidine blue) at day 3 and 7. Three independent experiments were performed in triplicates for each group and cell type. After confirming the normality of data distribution and exclusion of the outliers, data were analyzed with a univariate general linear model and post hoc Bonferroni test ( p < 0.05). Results In the MSC cultures, a slight DNA increase was observed between day 3 and 7 for both PU/HA-pNIPAM and PU/fibrin samples. At day 7, the highest amounts of DNA were found for the PU/fibrin group, followed by fibrin and PU groups ( Fig. 1a ). The amount of DNA was higher in the PU group than PU/HA-pNIPAM and HA-pNIPAM, suggesting a lower cell proliferation in the presence of the thermoreversible hydrogel. A similar DNA profile was obtained when hIVD cells were used instead of hMSCs. A significantly increased amount of GAG was observed in hMSC-seeded PU/HA-pNIPAM samples (Fig.1B) and there was an increase of GAG from day 3 to day 7. All other groups had a much lower amount of glycosaminoglycans and there was only a slight increase of GAG from day 3 to day 7. The GAG retention (GAG in sample divided by the sum of GAG in the sample and GAG released in the medium) at day 7 was comprised between 50% and 80% for all groups. Disk cells produced significantly less GAG in the PU/HA-pNIPAM system compared to hMSC, indicating that MSCs were more responsive to the combination of these two biomaterials ( Fig. 1B ). Moreover, the GAG retention at day 7 was lower with human IVD cells (20–60%) compared to hMSCs in all groups. This suggests that an early and higher GAG accumulation is associated to a better GAG retention in the hydrogel. This finding may be related to the fact that while MSCs were obtained from patients undergoing various types of surgeries, IVD cells were obtained from (degenerate) disks of patients undergoing total IVD replacement. The gene expression profile confirmed MSC chondrogenic differentiation with a strong upregulation of collagen type II and, to a lower extent, of aggrecan and SOX9 (compared to cells collected on the day of seeding) without significant differences between the two gels. Histological sections revealed cell migration from PU particles to the hydrogels. [Figure: see text] Conclusion Human disk cells from degenerating disks synthesized less GAG than hMSCs, indicating that MSCs may represent a suitable cell type for the biological repair of IVDs. A synergic effect for MSC differentiation was observed when a thermoreversible hyaluronan-based hydrogel was combined with polyurethane particles. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Mortisen D, et al. Biomacromolecules 2010;11:1261–1272 Peroglio M, et al. European Spine Journal Epub ahead of print Mauth C, et al. European Cells and Material 2009;18:27–38

TEMPERATURE SENSITIVITY OF COMPOSITE HYDROGEL PREPARED BY SURFACE GRAFT POLYMER OF NIPAAm AND BAMBOO CHARCOAL POWDER

This study aimed at fabricating a new type temperature sensor device by taking advantages of electrical conductivity of bamboo charcoal powder and temperature sensibility of NIPAAm hydrogel. The resistance of such a composite device will be affected by temperature. Bamboo charcoal powders were first subjected to oxygen plasma treatment. The treated bamboo charcoal powders were then UV graft polymerization with N-isopropylacrylamide (NIPAAm) monomer solution to be immobilized on the electrode which had previously been modified with plasma of tetramethyltin (TMT) and O2 gas mixture. Using simple environment test to measure resistance, the LCST of bamboo charcoal powders mixed with NIPAAm hydrogel was found to be 31°C. At ambient temperatures higher than LCST, the electrode resistance decreases. The surface morphology of composite hydrogel was observed by SEM.

The Preparation and Rheological Investigation of Polymer and Hydrogel Modified Drilling Mud

The authors carried out the study to prepare chitosan N-isopropylacrylamide hydrogel via heating and radiation processes. Properties investigation of prepared samples revealed that radiation prepared samples show higher yield and swelling ratios in comparison with the heating prepared ones. Effects of hydrogel addition to drilling mud on its important rheological properties such as apparent viscosity, plastic viscosity, and stress-strain behavior are measured. The rheological properties of hydrogel were compared with cellulosemethylcarboxyl and resins that are widely used in drilling fluid. The results demonstrate that whereas linear polymer effects on mud properties are more significant in polymer low concentration, prepared crosslinked hydrogel effects are more significant at high concentrations.

Preparation of hydrogels with rapid thermal response using liquid crystallite as template

To improve the temperature sensitivity of conventional poly(N-isopropylacrylamide) (PNIPA) hydrogel, a lyotropic liquid crystal based on polyoxyethylene 20 cetyl ether (Brij58,C16E20) was used as template to prepare nanostructured hydrogel. The structure, morphology, swelling behaviour and temperature sensitivity of confined PNIPA hydrogel were characterised. The prepared hydrogels presented honeycomb structure and rapid swelling rate. The time for losing water was greatly shortened. The thermal response measured by differential scanning calorimeters was improved markedly. Finally, as for oscillatory swelling/deswelling behaviours, rapid recovery was observed on alternating temperature from 20 to 37°C.

Preparation, characterisation and controlled drug release from thermosensitive hybrid hydrogels

Temperature sensitive hydrogels are probably the most commonly studied class of environmentally sensitive polymer systems in drug delivery research. In this study, polyvinyl alcohol (PVA) matrix with nanosized pores was obtained by treatment with silica and glutaraldehyde. Then, the internal pores of the dry PVA matrix were filled with poly(N-isopropylacrylamide) (PNIPAAm) hydrogels to form a thermoresponsive hybrid PVA/PNIPAAm hydrogel for controlled drug release. The morphology and functional groups of the hybrid hydrogel were characterised by SEM and Fourier transform infrared spectroscopy. The swelling kinetics and the temperature dependence of equilibrium swelling ratio in distilled water were also investigated. Rhodamine B was loaded to the hybrid hydrogels for release study, and the release rate was fast when the temperature was above the lower critical solution temperature of PNIPAAm. The release data suggest that an excellent controlled release can be achieved by the hybrid hydrogel without losing the intelligent properties of the PNIPAAm hydrogel.

Local Mechanical Stimulation of Mardin-Darby Canine Kidney Cell Sheets on Temperature-Responsive Hydrogel

Collective motion of cell sheets plays a role not only in development and repair, but also in devastating diseases such as cancer. However, unlike single-cell motility, collective motion of cell sheets involves complex cell-cell communication during migration; therefore, its mechanism is largely unknown. To elucidate propagation of signaling transduced by cell-cell interaction, we designed a hydrogel substrate that can cause local mechanical stretching of cell sheets. Poly (N-isopropyl acrylamide) (PNIPAAm) hydrogel is a temperature-responsive polymer gel whose volume changes isotropically in response to temperature changes below 37 °C. We designed a combined hydrogel substrate consisting of collagen-immobilized PNIPAAm as the local stimulation side and polyacrylamide (PAAm) as the non-stimulation side to assess propagation of mechanical transduction. Mardin-Darby canine kidney (MDCK) cells adhered to the collagen-immobilized PNIPAAm gel increased it area and were flattened as the gel swelled with temperature decrease. E-cadherin in these cells became undetectable in some domains, and actin stress fibers were more clearly observed at the cell base. In contrast, E-cadherin in cells adhered to the collagen-immobilized PAAm side was equally stained as that in cells adhered to the collagen-immobilized PAAm side even after temperature decrease. ERK1/2 MAPK activation of cells on the non-stimulated substrate occurred after partial stretching of the cell sheet suggesting the propagation of signaling. These results indicate that a change in the balance of mechanical tension induced by partial stretching of cell sheets leads to activation and propagation of the cell signaling.

Characterization of Fe3O4 and Fe2O3 ferrogels prepared under uniform magnetic field

ABSTRACTWe compare the characteristics of ferrogels prepared with and without the presence of a uniform magnetic field using Fe3O4 and Fe2O3 nanoparticles immobilized in hydrogels of N-isopropylacrylamide. The spatial distribution and agglomeration of the nanoparticles within the ferrogels were investigated using ultra small angle x-ray scattering (USAXS) and transmission electron microscopy (TEM). Hydrated ferrogels were also studied for magnetization using direct current superconducting quantum interference device (DC-SQUID). Volume size distribution resulting from USAXS data of the Fe3O4-ferrogel prepared under a uniform 225 G magnetic field showed a single broad peak appreciably different from that prepared without magnetic field with three distinct peaks. Volume size distributions resulting from USAXS data of the Fe2O3-ferrogel prepared with and without the presence of a uniform magnetic field both similarly show two peaks. Nanoparticle agglomeration was also determined by analyzing TEM images of ferrogel samples. DC-SQUID measurements of Fe3O4-ferrogel prepared in the presence of a uniform magnetic field showed 9% higher magnetization compared to the Fe3O4-ferrogel prepared without magnetic field. Similarly, DC-SQUID measurements of Fe2O3-ferrogel prepared in the presence of a uniform magnetic field showed 3% higher magnetization compared to the Fe2O3-ferrogel prepared without magnetic field. Thus, the presence of a uniform magnetic field during ferrogel polymerization can enabled the enhancement of the magnetoelastic property of the ferrogel.

Preparation and Properties of Thermo-Sensitive Molecularly Imprinted Hydrogels

In this paper, D-naproxen imprinted poly(N-isopropylacrylamide) (PNIPAAm)hydrogels was prepared by thermal polymerization method with D-naproxen as the template and N-isopropylacrylamide (NIPAAm) as functional monomer, N,N-methylene bisacrylamide (MBAA) as cross-linking agent. The thermal properties of the hydrogels were characterized by Differential Scanning Calorimetry (DSC), and the swelling behaviors, thermo-sensitivity and adsorption were studied respectively. The results showed that the D-naproxen imprinted hydrogels have good temperature-response and the LCST is about 33°C. The molecularly imprinted have good adsorbability to D-naproxen.

A Novel Structure Having Linear Poly(N-Isopropylacrylamide) Chains with Rapid Response to Temperature Changes

In this article, a novel structure poly(N-isopropylacrylamide) (PNIPAM) hydrogel, which is featured with both ends of linear PNIPAM chains being grafted onto semicircular and cross-linked PNIPAM chains, has been successfully prepared in a three-step process by a method of sequential synthesis for the first time. The proposed hydrogel displays faster and hydration/dehydration dynamic response to temperature cycling owing to linear PNIPAM chains to form big-hole structure. This work may be highly attractive for targeting drug delivery systems, polymeric machinery, and sensors and so on.

PHENOMENOLOGICAL MODEL FOR COUPLED ALCOHOL AND TEMPERATURE SENSITIVE HYDROGELS

A mathematical model for stimuli-sensitive hydrogels in a water-alcohol solution is presented and analyzed, in which a new polymer-solvent interaction parameter is proposed to capture the deformation of the hydrogel due to changes in the external alcohol content and temperature. The nature of this parameter is determined in the limit of pure dilatation for poly(N-isopropylacrylamide) hydrogels immersed in tempered water-methanol and -ethanol solutions. Overall, good agreement between the resulting model predictions and experiments is achieved; the transition temperatures and "re-entrant phenomenon" are also captured reasonably well. The herein derived expression for the polymer-solvent interaction parameter can be introduced into more generic transient models that also account for fluxes of the relevant field variables.

Fiber Endoscopes Utilizing Liquid Tunable-Focus Microlenses Actuated Through Infrared Light

We report on prototype fiber endoscopes with tunable-focus liquid microlenses integrated at their distal ends and actuated through infrared (IR) light. Tunable-focus microlenses allow minimal back-and-forth movements of the scopes themselves and different depths of focus (DOFs), thus having spatial depth perception in the obtained images. The liquid microlens was formed by a water-oil meniscus pinned at a hydrophobic-hydrophilic boundary at an aperture. IR light-responsive hydrogel microstructures were formed by photopatterning thermo-responsive N-isopropylacrylamide hydrogel with entrapped IR light absorbing gold nanoparticles. The volumetric change in the hydrogel microstructures regulated the pressure difference across the water-oil interface and thus varied its focal length. The operations of the microlenses were realized through light transmitted via optical fibers. The images obtained from the microlenses were transferred via image fiber bundles. For two alignments between the hydrogel structures and the fibers, the response times of the microlenses are 65 and 20 s, respectively. Images of the simulated polyps in simulated colons were obtained. The range of focal length of a typical microlens was from 52 to 8 mm. The angle of view of an endoscope was from 77° to 128°. A microlens array could potentially be utilized to simultaneously obtain different DOFs and to increase the field of view.

Versatile Pectin Grafted Poly (N-isopropylacrylamide); Modulated Targeted Drug Release

This study describes synthesis and optimization of pectin grafted poly(N-isopropylacrylamide) hydrogels as vehicles for colon-targeted theophylline model drug release. The gels were prepared in the presence of N, N′–methylenebisacrylamide (MBAA) crosslinker and ceric ammonium nitrate (CAN) initiator under N2 atmosphere. Optimum conditions, in terms of percent of grafting (%G), were determined as follows: pectin = 1.0 g, [NIPAAm] = 26.51 mM, [MBAA] = 0.65 mM, [CAN] = 0.073 mM, polymerization temperature = 30°C and time = 4.0 h. Hydrogels were characterized by FTIR, TGA, DSC, XRD and SEM. The formed hydrogel did not have a thermo-sensitivity behavior. The in vitro percent drug release was studied in terms of different percent of grafting and different polymerization temperatures under two pH values namely 5.5 and 7.4. Conclusively, the optimum colon-targeted vehicle properties that provide the least drug release at pH5.5 and the most drug release at pH7.4 were as follows: [NIPAAm] = 26.51 mM and [MBAA] = 0.56 mM, polymerization temperature = 30°C and %G = 55.5.

Diffusion of poly(ethylene glycol) and ectoine in NIPAAm hydrogels with confocal Raman spectroscopy

The diffusion behavior of poly(ethylene glycol) (PEG) in N-isopropylacrylamide (NIPAAm) hydrogels was investigated using confocal Raman spectroscopy with regard to temperature (25°C, 30°C and 35°C), PEG concentration (10 and 40 wt.%), PEG molecular weight (2,000 and 12,000 g/mol) and addition of the compatible solute ectoine (0.1 and 2 wt.%). Swelling and shrinking of the gels was observed by means of confocal Raman spectroscopy. The swelling behavior of NIPAAm gels in aqueous solutions of PEG and ectoine was found to resemble the swelling behavior in pure water with regard to temperature, i.e., the gel shrinks with increasing temperature. However, the presence and concentration of PEG and ectoine influence the swelling behavior by lowering the volume phase-transition temperature of the gel and facilitating shrinking. In some cases, a re-swelling of the gel was observed after the initial shrinking at the onset of PEG diffusion, which can be explained by PEG changing the chemical potential in the gel phase as it diffuses into the sample allowing the water to re-enter. The expulsion of water from the gel during shrinking and the so-caused increase of PNIPAAm and PEG concentrations in some cases led to the PEG diffusion seemingly being faster in more shrunken gels despite of their higher diffusion resistance.

Preparation and Characterization of Thermo-Sensitive Hydroxypropylmethyl Cellulose/Poly (N-Isopropylacrylamide) Hydrogel

The best is to read these instructions and follow the outline of this text. Thermo-sensitive hydrogels based on linear HPMC and cross-linked PNIPAAm were prepared by the semi-IPN technique. The interior morphology of hydrogels was investigated by fluorescent microscope. The hydrogels were characterized by Fourier transform infrared (FTIR). The thermo-sensitivity, equilibrium swelling rate and swelling dynamics of these hydrogels were investigated. The chemical compositions and structures of the semi-hydrogels were similar to each other, as measured by FTIR. The results indicated that the swelling ratio of the hydrogel decreased with increasing temperature. In pH 7.4 buffer solution (37°C ), when the weight ratio of HPMC to NIPAAm was 1/100, the swelling ratio was the maximum. In comparision with a conventional PNIPA hydrogel, the semi-IPN hydrogel synthesized with hydroxypropyl-methyl cellulose exhibits a much faster response rate to temperature changes. For example, PNI-H05 loses 87% water within 5min, whereas the conventional hydrogel loses only about 25% water within 5 min. and about 50% water within 50 min.

Temperature and acid/base-driven dual switching of poly(N-isopropylacrylamide) hydrogel with Azo dye

A thermoresponsive poly(NIPAM-co-Azo) hydrogel labeled with azo dye was prepared by typical radical copolymerization. The lower critical solution temperature (LCST) behavior was investigated by means of UV-vis spectroscopy which allows the measurement of the phase transition from 25 to 45 °C in aqueous solution. The poly(NIPAM-co-Azo) copolymer also exhibited sizeable color change when used a acid/base-induced molecular switch. This material can act as water soluble dual sensor for both temperature and acid/base.

Nanoparticle-crosslinked hydrogels as a class of efficient materials for separation and ion exchange

We describe the remarkable capabilities of polymer–nanoparticle hybrids for cation binding and separation. The materials investigated here are hydrogels of N-isopropylacrylamide (NIPA) prepared using nanoparticles of the synthetic clay, Laponite® RD, as the crosslinkers. When immersed into an aqueous solution containing a cationic amine-based dye (methylene blue), the gel rapidly soaks up the dye from solution. Additionally, the gel is able to selectively extract the above cationic dye from a mixture of cationic and anionic dyes. These ion-exchange properties are driven by the strong binding affinity of certain cations for the anionic surfaces of the clay nanoparticles within the gel matrix. A comparison of the nanostructured gel with a typical cation-exchange resin (polystyrene-sulfonate) shows that the former is quicker and more efficient at extracting cationic species from solution. We also show that the solute adsorbed within the gel can be further concentrated by exploiting the shrinking property of NIPA gels when heated. Additionally, we demonstrate the disassembly of Laponite-crosslinked gels by exposure to an organic solvent or a hydrophilic oligomer, which allows the adsorbed solute to be released and thereby recovered.

Immobilization of lipase from Candida rugosa into copolymer hydrogels of poly(N-isopropylacrylamide-co-itaconic acid) synthesized in the presence of surfactants

To overcome the problems of free enzyme application as catalysts in chemical reactions, i.e. high costs of isolation and purification processes, high sensitivity to process conditions, insufficient enzyme stability etc., a different immobilization techniques are to be used. Immobilization to/within solid support improves enzyme stability decreasing its denaturation. This paper deals with hydrogels of N-isopropylacrylamide and itaconic acid with incorporated nonionic surfactants (Triton X-100, Brij 30 and Tween 80) synthesized in distilled water at room temperature by free radical polymerization. These hydrogels were used as supports for immobilization of enzyme, lipase from Candida rugosa by post-entrapment method. The aim was to investigate the effect of the nonionic surfactants on the lipase binding capacity, as well as on its hydrolytic activity. In order to characterize the obtained hydrogels FT-IR analysis has been performed. Further, the swelling behaviour of these samples in buffer solution of pH 6.80 has been investigated. The dynamic - mechanical properties of hydrogels and detailed have been studied, too. The immobilized lipase showed somewhat reduced hydrolytic activity, as compared to the activity of free lipase as well as in comparison to the lipase immobilized to the reference sample (sample synthesized under the same polymerization conditions, but in the absence of surfactants). It was concluded that the addition of surfactants increased the hydrogel mesh size. The surfactant addition did not affect the dynamic - mechanical properties of the investigated hydrogels. The largest percentage of specific activity and yield of activity were presented by the reference sample, too. It is obvious that the absence of surfactants charged groups has no influence on the lipase binding capacity, and the obtained activity yields are to be expected.

Role of Thermo-responsiveness and Poly(ethylene glycol) Diacrylate Cross-link Density on Protein Release from Poly(N-isopropylacrylamide) Hydrogels

Thermo-responsive hydrogels have shown promise as injectable materials for local drug delivery. However, the phase-induced changes in polymer properties of N-isopropylacrylamide (NIPAAm) can pose additional challenges for achieving controlled protein release. In this work, thermo-responsive hydrogels derived from NIPAAm and cross-linked with poly(ethylene glycol) diacrylate (PEG-DA) were synthesized via free radical polymerization. The volume phase transition temperature (VPTT) of the hydrogels ranged from 32.9°C to 35.9°C. Below the VPTT, swelling ratios of the hydrogels decreased with cross-linker concentration, and showed a sharp drop (at least 4-fold) upon phase change. Protein encapsulation efficiency was high (84–90%) and decreased with cross-linker concentration. Release of bovine serum albumin, a model protein, at body temperature was significantly higher than at room temperature (67% at 37°C compared to 44% at 23°C after 48 h). The release kinetics of proteins from the hydrogels were initially expected to be a function of cross-link density. However, at the hydrogel compositions explored in this work, protein release did not change significantly with cross-linker mol fraction. The thermo-responsive hydrogels offer a promising platform for the localized delivery of proteins.

Tunable microlens arrays actuated by various thermo-responsive hydrogel structures

We report on liquid-based tunable-focus microlens arrays made of a flexible polydimethylsiloxane (PDMS) polymer. Each microlens in the array is formed through an immiscible liquid–liquid interfacial meniscus. Here deionized water and silicone oil were used. The liquids were constrained in the PDMS structures fabricated through liquid-phase photopolymerization for molding and soft lithography. The microlenses were actuated by thermo-responsive N-isopropylacrylamide (NIPAAm) hydrogel microstructures and could be tuned individually by changing the local temperature. The NIPAAm hydrogels expanded and contracted, absorbing and releasing water, at different temperatures. Thus the pressure across the water–oil interface in the microlenses varied responding to the temperature, tuning their corresponding focal lengths. The microlens diameter was 2.4 mm. The typical microlens focal length was measured to be from 8 to 60 mm depending on the temperature. The microlens response time actuated by different structures and components of the NIPAAm hydrogels were compared. The normalized light intensities of the microlens focused spots were measured, matching well with a Zemax simulation, to study the microlens spherical aberrations. The NIPAAm hydrogel durability was also measured.

Synthesis of the Functional Hydrogels: Poly(N-isopropylacrylamide) Threaded onto the PEG Backbones Via RAFT

Functional poly(N-isopropylacrylamide) (PNIPAM) hydrogels were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization of NIPAM in the presence of four-arm poly(ethylene glycol) (4A-PEG) as backbone and 4-cyanopentanoic acid dithiobenzoate functional α -cyclodextrin threaded onto the PEG as chain transfer reagent (CTA).The structure of the hydrogels was characterized in detail with FTIR techniques. The analytical results demonstrated that α -cyclodextrin remains in as-obtained hydrogels. The swelling behavior was investigated and the functional hydrogels (functional gels) showed accelerated shrinking kinetics and higher swelling ratio comparing with conventional hydrogel (CG). It could be attributed to the presence of dangling chains. The hydrogel exhibited rapid swelling and deswelling kinetics. In principle, the hydrogel might find a number of applications including an on-off system and drug delivery systems.