Temperature‐Sensitive Poly(N‐isopropylacrylamide) Hydrogels with Macroporous Structure and Fast Response Rate

Macroporous temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPA) hydrogels were prepared by a novel phase‐separation technique to improve the response properties. In comparison with a conventional PNIPA hydrogel prepared in water, these macroporous hydrogels, prepared by polymerization in aqueous sucrose solutions, have higher swelling ratios at temperatures below the lower critical solution temperature and exhibit much faster response rates to temperature changes.

Scanning electron microscopy image of the surface of a PNIPA hydrogel, prepared in 1.50 M aqueous sucrose solution.     

Dual responsive poly(N‐isopropylacrylamide) hydrogels having spironaphthoxazines as pendant groups

Stimuli responsive hydrogels (PNIPAAm‐MSp) with a thermoresponsive backbone and photochromic pendant groups were synthesized via free radical polymerization using N‐isopropylacrylamide, modified spironaphthoxazines with a polymerizable double bond (MSp) as photochromic monomer, the crosslinker N,N′‐methylenebis(acrylamide) and the initiator 2,2′‐azobis(isobutyronitrile) in dimethylsulfoxide. The polymers are dual responsive, in that poly(N‐isopropylacrylamide) (PNIPAAm) responds to temperature changes whereas the pendant spironaphthoxazines respond to light. Irradiation enhanced the water absorption of the polymers while increases in temperature decreased it. The irradiated PNIPAAm‐MSp showed best water absorption at 0 °C (Q = 3.25) while water desorbed at higher temperatures (35 °C; Q = 0.30); where Q is the amount of water absorbed by a gram of dry polymer. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3318–3325, 2009     

A Novel Approach to Prepare Porous Poly(N‐isopropylacrylamide) Hydrogel with Superfast Shrinking Kinetics

In this study, the hydrophobic liquid template method was firstly used to prepare temperature sensitive, porous poly(N‐isopropylacrylamide) (PNIPAAm) hydrogel. During the radical polymerization, hydrophobic polydimethylsiloxane (PDMS) and surfactant sodium dodecyl sulfate (SDS) were used as liquid templates and stabilizer, respectively. After removal of the liquid templates, porous PNIPAAm hydrogel was obtained. This gel exhibited superfast shrinking properties when being transferred from below to above the lower critical solution temperature (LCST), which was ascribed to the interconnected porous structures.

     

Synthesis and characterization of stimuli‐sensitive micro‐ and nanohydrogels based on photocrosslinkable poly(dimethylaminoethyl methacrylate)

The aim of this work was the development of a versatile route for the preparation of temperature‐ and pH‐responsive hydrogels with small dimensions. The copolymerization of N,N‐dimethylaminoethyl methacrylate with various amounts (5 and 10 mol %) of dimethylmaleimidoethyl methacrylate in solution with 2,2′‐azobisisobutyronitrile as an initiator is described. The structural and molecular characterization of the copolymers was performed with proton nuclear magnetic resonance, Fourier transform infrared, and ultraviolet spectroscopy, as well as size exclusion chromatography. Differential scanning calorimetry and thermogravimetry were used for the thermal characterization of the copolymers. Micro‐ and nanohydrogels of the copolymers were prepared by photocrosslinking. The gels obtained by photocrosslinking were characterized with a combination of surface plasmon resonance and optical waveguide spectroscopy, dynamic light scattering, and scanning electron microscopy. The hydrogels showed temperature‐ and pH‐responsive behavior. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 669–679, 2007     

Structural design of stimuli‐responsive bioconjugated hydrogels that respond to a target antigen

Stimuli‐responsive bioconjugated hydrogels that can respond to a target antigen (antigen‐responsive hydrogels) were prepared by introducing antigen‐antibody bindings as reversible crosslinks into the gel networks. The preparation conditions of the antigen‐responsive hydrogels and the mechanism of the antigen‐responsive behavior were investigated, focusing on bioconjugated hydrogel structures. This article also focuses on the effect of semi‐interpenetrating polymer network (semi‐IPN) structures on the antigen‐responsive swelling/shrinking behavior of bioconjugated hydrogels with antigen‐antibody bindings. The preparation conditions and the network structures of the bioconjugated hydrogels are discussed in relation to designing antigen‐responsive hydrogels. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2144–2157, 2009     

Thermo-responsive chitosan-graft-poly(N-isopropylacrylamide) injectable hydrogel for cultivation of chondrocytes and meniscus cells

A thermo-responsive comb-like polymer with chitosan as the backbone and pendant poly(N-isopropylacrylamide) (PNIPAM) groups has been synthesized by grafting PNIPAM-COOH with a single carboxy end group onto chitosan through amide bond linkages. The copolymer exhibits reversible temperature-responsive soluble-insoluble characteristics with the lower critical solution temperature (LCST) being at around 30 degrees C. Results from SEM observations confirm a porous 3D hydrogel structure with interconnected pores ranging from 10 to 40 microm at physiological temperature. A preliminary in vitro cell culture study has demonstrated the usefulness of this hydrogel as an injectable cell-carrier material for entrapping chondrocytes and meniscus cells. The hydrogel not only preserves the viability and phenotypic morphology of the entrapped cells but also stimulates the initial cell-cell interactions.     

UV-photocrosslinking of inulin derivatives to produce hydrogels for drug delivery application

In this work, INU, a natural polysaccharide, has been chemically modified in order to obtain new photocrosslinkable derivatives. To reach this goal, INU has been derivatized with MA thus obtaining four samples (INU-MA derivatives) as a function of the temperature and time of reaction. An aqueous solution of the derivative INU-MA1 was irradiated by using a UV lamp with an emission range from 250 to 364 nm and without using photoinitiators. The obtained hydrogel showed a remarkable water affinity but it underwent a partial degradation in simulated gastric fluid. To overcome this drawback, INU-MA1 was derivatized with SA thus obtaining the INU-MA1-SA derivative designed to produce a hydrogel showing a low swelling and an increased chemical stability in acidic medium. Ibuprofen, as a model drug, was loaded by soaking into INU-MA1 and INU-MA1-SA hydrogels and its release from these matrices was evaluated in simulated gastrointestinal fluids. INU-MA1 hydrogel showed the ability to quickly release the entrapped drug thus indicating its potential as a matrix for an oral formulation. INU-MA1-SA hydrogel showed a pH-responsive drug delivery. Therefore it is a promising candidate for controlled drug release in the intestinal tract.     

Poly(N‐isopropylacrylamide) Nanoparticle‐Incorporated PNIPAAm Hydrogels with Fast Shrinking Kinetics

Summary: Novel temperature‐responsive poly(N‐isopropylacrylamide) (PNIPAAm) nanoparticle‐containing PNIPAAm hydrogels were prepared by radical polymerization. In comparison with conventional PNIPAAm hydrogels, the PNIPAAm gels thus prepared exhibit much faster response rates as the temperature is raised above the lower critical solution temperature. The improved properties are a result of the incorporation of PNIPAAm particles, which first shrink and then generate pores for water molecules to be quickly squeezed out of the bulky PNIPAAm gels.

Schematic illustration of the shrinking process: (I) First PNIPAAm particles shrink and generate pores; (II) the bulky gels then shrink further at a rapid rate.     

Stimuli‐responsive polymer hydrogels containing partially exfoliated graphite

In this work, a new stimuli‐responsive composite polymer hydrogel containing partially exfoliated graphite was prepared by frontal polymerization. The materials obtained were characterized by differential scanning calorimetry, RAMAN, scan electron microscopy, transmission electron microscopy, atomic force microscopy, and in terms of swelling behavior. It was found that the maximum temperature reached by the polymerization front and the lower critical solution temperature are affected by the graphite content. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Ru(II)(tpy)2‐functionalized hydrogels: Synthesis,reversible responsiveness,and coupling with the belousov‐zhabotinsky reaction

This work aims at developing an approach to Ru(II)(Tpy)₂‐functionalized hydrogels and exploring the coupling of the hydrogels with the Belousov‐Zhabotinsky (BZ) reaction. Based on free radical polymerization, two synthetic routes are developed. The first one is the direct gelation by copolymerization of acrylamide as hydrophilic component and Ru(II)(Tpy)₂ as the functional group. The second one is carried out through a combined approach. A terpyridine‐containing hydrogel is first prepared and then post‐functionalized by coordination between Ru(III)(Tpy)Cl₃ and terpyridine groups in the hydrogel network. Utilizing the synthetic hydrogels, the reversible redox responsiveness, the coupling with the BZ reaction, the occurrence and the self‐oscillating properties of the BZ reaction in the hydrogel networks are studied. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2214–2222     

Thermoresponsive super water absorbent hydrogels prepared by frontal polymerization

Frontal polymerization was used as an alternative technique for the preparation of super water absorbent hydrogels obtained from acrylamide and 3‐sulfopropyl acrylate, potassium salt (SPAK) in the presence of N,N′‐methylene‐bisacrylamide as a crosslinker. All samples were synthesized in dimethyl sulfoxide, and their swelling behavior in water was investigated. It was found that their features are dependent on the monomer ratio used, which influenced the porous morphology, and consequently, the swelling capability. The swelling ratio ranges from about 1000% for the acrylamide homopolymer up to 14,000% for the sample containing 87.5 mol % of SPAK, thus indicating that this parameter can be easily tuned by using the appropriate monomer ratio. The affinity towards water was eventually confirmed by contact angle analysis. Polymer hydrogels made from at least 62.5 mol % SPAK exhibit a thermoresponsive behavior, with a lower critical solution temperature of ～30 °C. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2486–2490, 2010     

Synthesis and characterization of thermoresponsive poly(ethylene glycol)‐based hydrogels and their magnetic nanocomposites

Temperature‐responsive hydrogels are one of the most widely studied types of stimuli‐responsive hydrogel systems. Their ability to transition between their swollen and collapsed states makes them attractive for controlled drug delivery, microfluidic devices, and biosensor applications. Recent work has shown that poly(ethylene glycol) (PEG) methacrylate polymers are temperature‐responsive and exhibit a wide range of lower critical solution temperatures based on the length of ethylene glycol units in the macromer chain. The addition of iron oxide nanoparticles into the hydrogel matrix can provide the ability to remotely heat the gels upon exposure to an alternating magnetic field (AMF). In this work, diethylene glycol (n = 2) methyl ether methacrylate and PEG (n = 4.5) methyl ether methacrylate copolymers were polymerized into hydrogels with 5 mol % PEG 600 (n = 13.6) dimethacrylate as the crosslinker along with 5 wt % iron oxide nanoparticles. Volumetric swelling studies were completed from 22 to 80 °C and confirmed the temperature‐responsive nature of the hydrogel systems. The ability of the gels to collapse in response to rapid temperature changes when exposed to an AMF was demonstrated showing their potential use in biomedical applications such as controlled drug delivery and hyperthermia therapy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3229–3235, 2010     

Synthesis and characterization of graphene‐containing thermoresponsive nanocomposite hydrogels of poly(N‐vinylcaprolactam) prepared by frontal polymerization

Thermoresponsive poly(N‐vinylcaprolactam) nanocomposite hydrogels containing graphene were successfully prepared by frontal polymerization. High concentration of graphene (5.0 mg/mL) was obtained by direct graphite sonication in the self‐same liquid monomer, thus avoiding any chemical manipulation and obtaining “real” graphene as nanofiller instead of one of its more or less oxidized derivative, which is what generally reported in published reports. Furthermore, the corresponding nanocomposites were obtained without using any solvent to be eventually removed. The materials were fully characterized by RAMAN, SEM, and TEM, and their swelling behavior and rheological properties were investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and physicochemical characterization of biodegradable and pH‐responsive hydrogels based on polyphosphoester for protein delivery

In this work, a series of biodegradable and pH‐responsive hydrogels based on polyphosphoester and poly(acrylic acid) are presented. A novel biodegradable macrocrosslinker α‐methacryloyloxyethyl ω‐acryloyl poly(ethyl ethylene phosphate) (HEMA‐PEOP‐Ac) was synthesized by first ring‐opening polymerization of the cyclic monomer 2‐ethoxy‐2‐oxo‐1,3,2‐dioxaphospholane using HEMA as the initiator and Sn(Oct)₂ as catalyst, and subsequent conversion of hydroxyl into vinyl group. The hydrogels were then fabricated by the copolymerization of the macromonomer with acrylic acid, and their swelling/deswelling and degradation behaviors were investigated. The results demonstrated that the crosslinking density and pH values of media strongly influenced both the swelling ratio and the degradation rate of the hydrogels. The rheological properties of these hydrogels were also studied from which the storage modulus (G′) showed clear dependence on the crosslinking density. MTT and “live/dead” assay showed that these hydrogels were compatible to fibroblast cells, not exhibiting apparent cytotoxicity even at high concentrations. Moreover, in vitro bovine serum albumin release from these hydrogels was also investigated, and it could be found that the release profiles showed a burst effect followed by a continuous release phase, and the release rate was inversely proportional to the crosslinking density of hydrogels. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1919–1930, 2010     

In situ Synthesis of Magnetic Iron Oxide Nanoparticles in Thermally Responsive Alginate‐Poly(N‐isopropylacrylamide) Semi‐Interpenetrating Polymer Networks

A novel semi‐interpenetrating polymer network based on alginate and poly(N‐isopropylacrylamide) (PNiPAAm) has been synthesized that shows response to temperature and magnetic fields. Highly homogeneous porous hydrogels are obtained by copolymerizing N‐isopropylacrylamide and bis‐acrylamide in the presence of an aqueous alginate solution. The synthesis of magnetic iron oxides by in‐situ oxidation of iron cations coordinated to the alginate network results in a hydrogel with an enhanced deswelling rate with respect to pure PNiPAAm.

     

Temperature-sensitive polyamidoamine dendrimer/poly(N-isopropylacrylamide) hydrogels with improved responsive properties

Novel temperature-sensitive poly(N-isopropylacrylamide)/amine-terminated polyamidoamine dendrimer G6-NH2 hydrogels with fast responsive properties were synthesized by forming semi-interpenetrating polymeric networks. In contrast to the conventional PNIPA hydrogel, these new gels showed rapid shrinking rate at the temperature above lower critical solution temperature (LCST), and exhibited higher equilibrium swelling ratio at room temperature. All these properties might be attributed to the incorporation of polyamidoamine dendrimer G6-NH2, which forms water-releasing channels and increases the hydrophilicity of PNIPA network. The novel hydrogels have potential applications in drug and gene delivery.     

3‐D Interdigitated electrodes for uniform stimulation of electro‐responsive hydrogels for biomedical applications

Stimuli‐responsive hydrogels are continuing to increase in demand in biomedical applications. Occluding a blood vessel is one possible application which is ideal for a hydrogel because of their ability to expand in a fluid environment. However, typically stimuli‐responsive hydrogels focus on bending instead of radial uniform expansion, which is required for an occlusion application. This article focuses on using an interdigitated electrode device to stimulate an electro‐responsive hydrogel in order to demonstrate a uniform swelling/deswelling of the hydrogel. A Pluronic‐bismethacrylate (PF127‐BMA) hydrogel modified with hydrolyzed methacrylic acid, in order to make it electrically responsive, is used in this article. An interdigitated electrode device was manufactured containing Platinum electrodes. The results in this paper show that the electrically biased hydrogels deswelled 230% more than the non‐biased samples on average. The hydrogels deswelled uniformly and showed no visual deformations due to the electrical bias. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1523–1528