Copolymer Hydrogels Research Articles

Dynamical modeling and experimental aspects of multi-responsive hydroxy-functional methacrylate-based gels with tunable swelling induced by multivalent ions

Novel materials displaying multi-responsive property were developed by forming crosslinked copolymer systems that exhibit distinct temperature, pH and salt-sensitivity independently. An investigation of the mechanical properties of a novel multi-responsive poly(hydroxypropyl methacrylate) (PHPMA)-based hydrogel system was carried out with two major objectives. First was to study the effect of various preparation conditions; reaction temperature, comonomer content on the elasticity as well as on the absorbency of resulting hydroxy-functional methacrylate-based gels and the second was to interpret their water uptake data by various kinetic models. Experiments were conducted to characterize the equilibrium swelling and temperature/pH-dependent phase transitions of PHPMA-based copolymeric gels prepared by radical crosslinking copolymerization in aqueous solution with tetraethyleneglycol dimethacrylate (TEGDMA) as crosslinker. The aqueous equilibrium swelling properties of PHPMA hydrogels and cryogels containing methacrylate-based comonomer were described using N,N-dimethylaminopropyl methacrylate (DMAEMA) having weakly basic cationic groups. For PHPMA-based copolymeric hydrogels, the scaling laws relating the optimum preparation conditions with the crosslinking density N and the swelling degree qv were derived. Dynamic kinetics profiles were evaluated to outline the swelling/deswelling response of the resulting hydrogels and cryogels which presents useful information when designing specific applications that pursue or require the absorption of pH-sensitive or ionic-strength-sensitive molecules.

CO2 Stimuli-Responsive, Injectable Block Copolymer Hydrogels Cross-Linked by Discrete Organoplatinum(II) Metallacycles via Stepwise Post-Assembly Polymerization.

Supramolecular polymeric gels cross-linked by well-defined, discrete metal-organic macrocycles (MOMs) or metal-organic cages have become a prevailing topic within the field of supramolecular self-assembly. However, the realization of supramolecular polymeric hydrogels cross-linked by discrete organometallic architectures with good biocompatibility is still a great challenge. Herein, we present the successful preparation of CO2 stimuli-responsive, injectable block copolymer hydrogels cross-linked by discrete organoplatinum(II) metallacycles. Through the combination of coordination-driven self-assembly and stepwise post-assembly polymerization, star block copolymers (SBCPs) containing well-defined hexagonal metallacycles as cores were successfully prepared, which featured CO2 stimuli-responsive properties including CO2-triggered morphology transition and CO2-induced thermoresponsive behavior. Interestingly, the resultant SBCPs were capable of forming supramolecular hydrogels with MOMs as junctions near physiological temperature, which allowed the realization of a reversible gel-to-sol transformation through the removal and addition of CO2. More importantly, the resultant supramolecular hydrogels presented good cytocompatibility in vitro. Therefore, this study provides a new strategy for the construction of new "smart" supramolecular hydrogels with promising applications as biological materials.

Structured emulsion-templated porous copolymer based on photopolymerization for carbon capture

Porous hydrogel copolymers of acrylamide (AAM) and acrylic acid (AAC) were structured in the form of monoliths and granules. AAM-co-AAC porous copolymer monoliths were synthesized using high internal phase emulsion (HIPE) as template and photopolymerization. For granulation, photopolymerization was used for the fabrication of the AAM-co-AAC hydrogel, which was subsequently freeze-granulated. The structural analysis (FTIR and XRD) confirmed the successful synthesis of hydrogel copolymers. The CO2 uptake capacity of structured AAM-co-AAC copolymers was evaluated through adsorption and absorption mechanisms by volumetric and gravimetric methods, respectively. The granules exhibited the CO2 adsorption uptake of 0.8mmolg−1 at 25kPa and 298K. The CO2 and N2 adsorption data demonstrated that the hydrogel copolymers were selective for CO2. Furthermore, the granules were capable of capturing CO2 in the presence of water. The results of absorption of CO2 on water-swollen granules demonstrated that CO2-uptake capacity increases with increasing water content up to 1.8mmolg−1.

Multi-responsive hydrogels with UCST- and LCST-induced shrinking and controlled release behaviors of rhodamine B

By using a disulfide-functionalized crosslinker, a pH- and thermo-responsive 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer and a zwitterionic sulfobetaine methacrylate (SBMA) monomer were conjugated to fabricate a multi-responsive P(DMAEMA-SS-SBMA) copolymeric hydrogel. Apparent UCST and LCST volume transitions were observed in the P(DMAEMA-SS-SBMA) hydrogels with equivalent weight fractions of monomers. Different pore size and response sensitivity of shrunken structures below UCST and above LCST were visualized by SEM images. The hydrogel exhibited a highly swollen state with a swelling ratio of 17.8 and a pore size of 106μm at 45°C, they deswelled unequally at 5°C with a compact surface with pore size of 30μm and a loose bulk with pore size of 83μm, while they deswelled uniformly at 65°C with dense shrunken structure with small pore size of 12μm. The dual-thermoresponsive hydrogel was promising in controlled drug release. The initial drug release was predominantly controlled by diffusion, and the long-term release was influenced by the swelling ratio. Below UCST, the relatively hydrophilic shrunken structure and slow diffusion had a synergistic effect on the sustained release. Above LCST, the fast diffusion and the rapid “off” effect of hydrophobic skin layer resulted in a burst release. Additionally, pH-tunable swelling and redox-sensitive degradation were also observed.

Preparation and characterization of protein-resistant hydrogels for soft contact lens applications via radical copolymerization involving a zwitterionic sulfobetaine comonomer

We aimed to introduce hydrophilic sulfobetaine-type zwitterionic groups to macromolecular chains of copolymers to construct novel copolymer hydrogels with anti-protein-fouling performance that could be used as soft contact lens (SCL) materials. Using hydroxyethyl methacrylate (HEMA), N-vinyl pyrrolidinone (NVP) and sulfobetaine methacrylate (SBMA) as comonomers, several copolymer hydrogels with different SBMA contents, poly(HEMA-NVP-SBMA), are synthesized via radical copolymerization in an aqueous phase. Surface chemistry, structural morphologies, water contact angle (WCA), equilibrium water content (EWC), visible light transmittance and tensile mechanical properties are investigated. The prepared hydrogels exhibit a closed-type porous structure. With increasing SBMA content in the comonomer mixture, the prepared copolymer hydrogel pore size gradually increases up to the micron level, WCA tends to decrease, EWC tends to increase, and visible light transmittance slightly increases, but their tensile mechanical properties decline. The amounts of protein Lyz and BSA adsorbed on the copolymer hydrogels and on commercially available EASY DAY® SCLs as a control are also determined by protein adsorption tests. The amount of protein adsorbed on the copolymer hydrogel decreases with increasing SBMA content. For the hydrogel prepared using the comonomer mixture with 5.0 wt % SBMA, the amount of adsorbed Lyz is 0.91 μg/cm2, which corresponds to only 56.8% of the amount adsorbed on EASY DAY® SCLs. Thus, novel SCL materials with high water content and excellent anti-protein-fouling performance were efficiently constructed by introducing sulfobetaine-type zwitterionic groups into a traditional polymer hydrogel system.

Synthesis and characterization of 2‐hydroxyethylmethacrylate/2‐(3‐indol‐yl)ethylmethacrylamide‐based novel hydrogels as drug carrier with in vitro antibacterial properties

ABSTRACTIn this study, a new cationic monomer 2‐(3‐indol‐yl)ethylmethacrylamide (IEMA) derived from tryptamine was synthesized in a single step and characterized by Fourier transform infrared (FTIR), 1H‐NMR, and 13C‐NMR. Then, one‐step preparation of novel poly[2‐hydroxyethylmethacrylate‐c‐2‐(3‐indol‐yl)ethylmethacrylamide], or p(HEMA‐c‐IEMA), copolymeric hydrogels has been performed successfully with IEMA and 2‐hydroxyethylmethacrylate (HEMA) as monomers using free radical aqueous polymerization. The hydrogels were characterized with scanning electron microscopy, FTIR, elemental analysis, thermogravimetric analysis, and texture profile analysis instruments. p(HEMA‐c‐IEMA) hydrogels were used for swelling, diffusion, drug release, and antibacterial activity studies. The drug‐release behavior of the hydrogels was determined as a function of time at 37 °C in pH 1.2 and 7.2. The swelling and drug‐release studies showed that an increased IEMA amount caused a higher increase in swelling and drug‐release values. Additionally, zero‐order, first‐order, and Higuchi equation kinetic models were applied to the drug‐release data, and the data fit well in the Higuchi model, and the Peppas power‐law model was applied to the release mechanism. Finally, the antibacterial activities of the hydrogels were screened against Gram‐positive bacteria (Bacillus cereus and Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45550.

Temperature-responsive star-shaped copolymer hydrogels for co-delivery and sequential release of three contraceptives

Temperature-responsive star-shaped copolymer hydrogels for co-delivery and sequential release of three contraceptives

PVA-PAA hydrogel micro-carrier for the improvement of phase separation efficiency of biomass in wastewater treatment

Phase separation process is influenced by operational factors that can hardly be controlled. This paper demonstrates the results of a series of experiments aiming to solve these problems using polyvinyl-alcohol - poly-acrylic acid copolymer hydrogel micro-carrier for the adherence of microorganisms to achieve better settling properties of the biomass. The nitrification process was examined using hydrogel micro-carriers and conventional activated sludge flocks. The sedimentation properties of the two systems were compared indifferent conditions. Results show that the sedimentation properties of the immobilized system were more favorable than activated sludge flocks.

Simple Radical Polymerization of Poly(Alginate-Graft-N-Isopropylacrylamide) Injectable Thermoresponsive Hydrogel with the Potential for Localized and Sustained Delivery of Stem Cells and Bioactive Molecules.

In this study, thermoresponsive copolymers that are fully injectable, biocompatible, and biodegradable and are synthesized via graft copolymerization of poly(N-isopropylacrylamide) onto alginate using a free-radical reaction are presented. This new synthesis method does not involve multisteps or associated toxicity issues, and has the potential to reduce scale-up difficulties. Chemical and physical analyses verify the resultant graft copolymer structure. The lower critical solution temperature, which is a characteristic of sol-gel transition, is observed at 32 °C. The degradation properties indicate suitable degradation kinetics for drug delivery and bone tissue engineering applications. The synthesized P(Alg-g-NIPAAm) hydrogel is noncytotoxic with both human osteosarcoma (MG63) cells and porcine bone marrow derived mesenchymal stem cells (pBMSCs). pBMSCs encapsulated in the P(Alg-g-NIPAAm) hydrogel remain viable, show uniform distribution within the injected hydrogel, and undergo osteogenic and chondrogenic differentiation under appropriate culture conditions. Furthermore, for the first time, this work will explore the influence of alginate viscosity on the viscoelastic properties of the resulting copolymer hydrogels, which influences the rate of medical device formation and subsequent drug release. Together the results of this study indicate that the newly synthesized P(Alg-g-NIPAAm) hydrogel has potential to serve as a versatile and improved injectable platform for drug delivery and bone tissue engineering applications.

In Vivo Redox-Responsive Sol–Gel/Gel–Sol Transition of Star Block Copolymer Solution Based on Ionic Cross-Linking

Redox-responsive hydrogels have the potential for application in various fields, including biomedical science. We have developed a redox-responsive star block copolymer hydrogel based on iron ion cross-linking. The addition of the ferric ion (Fe3+) induced gelation of the star block copolymer solution within a few seconds, whereas the addition of the ferrous ion (Fe2+) did not. The resulting hydrogels cross-linked using Fe3+ showed storage moduli (G′) of 26–1400 Pa and were stable under physiological conditions for as long as 1 month. The cross-linking between the star arms produced by the addition of Fe3+ enabled a fast, redox-responsive sol–gel/gel–sol transition. Furthermore, the hydrogel showed excellent injectability and biocompatibility in vivo, resulting in a rapid sol–gel/gel–sol transition in subcutaneous tissues in response to redox stimuli, such as the administration of ascorbic acid or hydrogen peroxide.

Mechanical and metal adsorption properties of emulsion gel adsorbents composed of PEGDA-co-PEG hydrogels and tri-n-octylamine

A novel type of emulsion gel adsorbent consisting of a polymeric hydrogel containing randomly distributed oil microdroplets of an extractant was developed for metal separation. A copolymer hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA; cross-linking monomer) and polyethylene glycol (PEG), i.e., a PEGDA-co-PEG hydrogel, was developed; the hydrogel with PEGDA = 500 mol/m3 and PEG = 50 kg/m3 possessed improved flexibility and strength. The emulsion gel containing an amine extractant, tri-n-octylamine, successfully adsorbed Zn(II) ions. The metal–extractant complexation process and its pH dependence in the emulsion gel were comparable to those of the solvent extraction method. Investigation of the metal adsorption kinetics revealed that diffusion of the solute in the hydrogel phase is fast, and diffusion (accumulation) in the organic extractant phase is the rate-determining step.

In situ forming stereocomplexed and post-photocrosslinked acrylated star poly(ethylene glycol)-poly(lactide) hydrogels

Biodegradable acrylate end-group functionalized poly(ethylene glycol)-poly(lactide) (PEG-PLA) star block copolymer hydrogels were formed by the consecutive physical gelation through stereocomplexation of star shaped PEG-(PLLA)8 and PEG-(PDLA)8 enantiomers and UV photopolymerization. The 8-armed PEG-PLA star block copolymers were prepared by ring opening polymerization of lactide onto an amine end-group functionalized PEG with a molecular weight of 20kg/mol using stannous octoate as a catalyst. The degree of polymerization of the PLA blocks was 12 lactyl units and the end hydroxyl groups were reacted with acryloyl chloride to give the required acrylate end groups. Aqueous solutions of enantiomeric mixtures of the PEG-(PLA)8 macromonomers formed physically crosslinked hydrogels above a critical gel concentration of 4w/v%. Subsequent photopolymerization at 365nm in the presence of Irgacure 2959 resulted in gels with improved mechanical properties and hydrolytic stability. With 40% polymer mass loss after 45d in vitro, these hydrogels show excellent resistance against hydrolytic degradation and dissolution, which is believed to result from the combination of stable amide linkages between the PEG and PLA blocks and the high physical and chemical crosslink density owing to the star architecture.

Synthesis and characterization of acrylamide-based copolymeric hydrogel–silver composites: Antimicrobial activities and inhibition kinetics against E. coli

ABSTRACTA series of acrylamide (AAm)-based hydrogels containing acrylic acid, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), and vinyl imidazole (VI) comonomers were prepared by free radical polymerization. Silver nanoparticles were loaded to hydrogel systems through in situ reduction of silver nitrate in the presence of sodium borohydride as a reducing agent. The synthesized hydrogels and their composites were characterized using FTIR, scanning electron microscopy, EDX, and EDX-mapping. The antimicrobial activity of hydrogel–silver composite was determined using well agar and broth dilution tests. In the first stage, four different hydrogel–silver composites were evaluated against six different microorganisms using the well agar technique. The most effective hydrogel–silver composite among all tested was poly(AAm-co-VI-co-AMPS)-Ag, while the most sensitive and resistant microorganisms among all tested were Staphylococcus cerevisiae and S. aureus, respectively. Poly(AAm-co-VI-co-AMPS)-Ag composite was used in modeling the inhibition kinetic of Escherichia coli. The present study displays that hydrogel–silver composite has considerable antimicrobial activity, which deserves further investigation for use in clinic application and industrial processing.

In Situ Gold Nanoparticle Gradient Formation in a 3D Meso- and Macroporous Polymer Matrix.

Herein, the development and characterization of a 3D gradient structure of gold nanoparticles is described. The gradient of gold nanoparticles is made in situ in a macroporous nonionic block copolymer hydrogel matrix, through gold ion diffusion control. The polymer provides a matrix for diffusion of gold ions, acts as a template for controlling nanoparticle growth, and facilitates the in situ reduction of gold ions to gold nanoparticles. A clear gradient in gold nanoparticles is observed across the 3D space of the polymer matrix using scanning electron microscopy, fluorescence microscopy, atomic force microscopy, and thermogravimetric analysis. The particle gradient is further functionalized with both hydrophobic and hydrophilic groups via thiol-gold linkage to demonstrate the ability to form gradients with different chemical functionalities. Using additive manufacturing, the polymer can also be printed as a porous network with possible applications for 3D cell culturing in, e.g., biomaterials research.

Calcitonin-Loaded Thermosensitive Hydrogel for Long-Term Antiosteopenia Therapy.

Effective antiosteopenia therapy can be achieved by designing long-term protein/peptide drug delivery systems for bone trabecula restoration. Here we show that a complex of salmon calcitonin and oxidized calcium alginate (sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel for long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol-gel transition at body temperature. The sustained release of sCT from the in situ gelling system was determined by both the degradation of the hydrogel and the decomposition of the sCT-OCA complex. This system showed sustained effects in reducing serum calcium and bone trabecula reconstruction in the treatment of glucocorticoid-induced osteopenia in rats for approximately 30 days after a single subcutaneous injection, which may shed light on antiosteopenia therapy in the future.

Phase Transition Behavior of Poly(N-isopropylacrylamide-co-N,Ndimethylaminopropylacrylamide) Hydrogels

The copolymer hydrogel of N-isopropylacrylamide (NIPAAm) and N,N-dimethylaminopropylacrylamide (DMAPAA) was synthesized by free radical copolymerization. The phase transition behavior of p(NIPAAmco-DMAPAA) hydrogels as a function of temperature and SDS concentration was studied. The p(NIPAAmco-DMAPAA) hydrogels exhibited larger swelling capacity than the homo p(NIPAAm) hydrogel. The phase transition temperature of p(NIPAAm-co-DMAPAA) hydrogels increased with an increase of DMAPAA content. In aqueous SDS solution, the swelling capacity of p(NIPAAm-co-DMAPAA) hydrogel decreased with an increase of SDS concentration. The phase transition temperature of p(NIPAAm-co-DMAPAA) hydrogels was found to be almost independent of the SDS concentration.

In vitro evaluation of mucoadhesive and self-disinfection efficiency of (acrylic acid/polyethylene glycol)-silver nanocomposites for buccal drug delivery

A mucoadhesive drug delivery system can improve the effectiveness of a drug, allowing targeting and localization at a specific site. According to this assumption, γ-irradiation as eco-friendly technique was employed to synthesize (acrylic acid/polyethylene glycol) copolymer hydrogel of different compositions. Silver nanoparticles were prepared within (acrylic acid/polyethylene glycol) hydrogel network by means of in situ reduction of silver nitrate using sodium borohydride as a reducing agent. Swelling characteristics in distilled water and simulated saliva solution were studied as a function of copolymer composition and preparation irradiation dose. (Acrylic acid/polyethylene glycol) hydrogels and their developed Agº nanocomposites have been characterized using scanning electron microscope, thermogravimetric analysis, transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction. Mucoadhesive strength as well as self-disinfection efficiency expressed as antibacterial activity against different bacterial strains was evaluated. Propranolol HCl as model drug was used to evaluate the potential efficiency of the obtained (acrylic acid/polyethylene glycol)-Agº nanocomposites as mucoadhesive drug carrier. The obtained results showed that the (acrylic acid/polyethylene glycol)-Agº nanocomposites show a promising self-disinfection property, and the propranolol HCl–loaded composites were able to deliver the loaded drug in a sustainable manner that lasts for about 600 min.

Injectable thermosensitive hydrogel containing hyaluronic acid and chitosan as a barrier for prevention of postoperative peritoneal adhesion

Peritoneal adhesion is one of the common complications after abdominal surgery. Injectable thermosensitive hydrogel could serve as an ideal barrier to prevent this postoperative tissue adhesion. In this study, poly(N-isopropylacrylamide) (PNIPAm) was grafted to chitosan (CS) and the polymer was further conjugated with hyaluronic acid (HA) to form thermosensitive HA-CS-PNIPAm hydrogel. Aqueous solutions of PNIPAm and HA-CS-PNIPAm at 10%(w/v) are both free-flowing and injectable at room temperature and exhibit sol-gel phase transition around 31°C; however, HA-CS-PNIPAm shows less volume shrinkage after gelation and higher complex modulus than PNIPAm. Cell culture studies indicate both injectable hydrogel show barrier effects to reduce fibroblasts penetration while induce little cytotoxicity in vitro. From a sidewall defect-bowel abrasion model in rats, significant reduction of postoperative peritoneal adhesion was found for peritoneal defects treated with HA-CS-PNIPAm compared with those treated with PNIPAm and untreated controls from gross and histological evaluation. Furthermore, HA-CS-PNIPAm did not interfere with normal peritoneal tissue healing and did not elicit acute toxicity from blood analysis and tissue biopsy examination. By taking advantage of the easy handling and placement properties of HA-CS-PNIPAm during application, this copolymer hydrogel would be a potentially ideal injectable anti-adhesion barrier after abdominal surgeries.

Fluorescence enhancement thermoresponsive polymer luminescent sensors based on BODIPY for intracellular temperature

Herein, A water soluble, visible excited and simple-structured copolymer hydrogel, poly(NIPAM-co-BODIPY-AA), consisting of N-isopropylacrylamide (NIPAM) and derivative of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) units as thermoresponsive and polarity sensitive fluorescent signalling parts, respectively, has been synthesized. The copolymer exhibits weak fluorescence at temperature low than 35°C in aqueous solution, whereas the red fluorescence intensity (λem=605nm) increases with a 10 folds rise in temperature up to 47°C with an increase of average lifetime from 0.68ns up to 2ns in the thermal transition processes. The fluorescence intensity increased linearly with increasing physiology temperature (37–42°C). The resultant nanothermometer could feature a high and spontaneous uptaking into the BHK cells. The prepared nanothermometer which is user friendly can provide tools for unveiling intrinsic relationship between the intracellular temperature and could be used in further applications for the fluorescent temperature sensing included parts of physiological temperature range in living cells.

Fast-responsive monolithic hydrogels as draw agent for forward osmosis membrane process

ABSTRACTA monolithic copolymer hydrogel was synthesised by polymerising n-isopropylacrylamide and sodium acrylate in the presence of poly(sodium 4-styrenesulfonate) (PSSS) chains and studied as potential draw agent for forward osmosis (FO) process. The monolithic hydrogel synthesised from 19% NIPAM, 1% SA, and 15% PSSS at 60°C generated higher FO water flux and higher recovery rate than other hydrogels, due to improved membrane-hydrogel contact and water transport. In particular, the synthesised hydrogel draw agent achieved twice water flux compared with the particles. The monolithic hydrogel containing a smaller amount of water produced a higher water flux due to its high swelling pressure.