Dual pH‐ and temperature‐responsive hydrogels with extraordinary swelling/deswelling behavior and enhanced mechanical performances

pH‐ and temperature‐responsive semi‐interpenetrating nanocomposite hydrogels (NC hydrogels) were prepared with surface‐functionalized graphene oxide (GO) as the crosslinker, N‐isopropylacrylamide (NIPAM) as the monomer, and chitosan (CS) as an additive. The effects of 3‐(trimethoxysilyl)propylmethacrylate‐modified GO sheets and CS content on various physical properties were investigated. Results show that PNIPAM/CS/GO hydrogels undergo a large volumetric change in response to temperature. Swelling ratios of PNIPAM/CS/GO hydrogels are much larger than those of the conventional organically crosslinked PNIPAM hydrogels. The deswelling test indicates that the deswelling rate was greatly enhanced by incorporating CS into the hydrogel network and using the surface‐functionalized GO as the crosslinker. The pH‐sensitivity of PNIPAM/CS/GO hydrogels is evident below their volume phase transition temperature. Moreover, the PNIPAM/CS/GO hydrogels have a much better mechanical property compared with traditional hydrogels even in a high water content of 90%. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41530.     

Hybrid double‐network hydrogel based on poly(aspartic acid) and poly(acryl amide) with improved mechanical properties

Hydrogels usually have a smaller mechanical strength and toughness than generic polymeric materials. Therefore, many studies report improvements for mechanical properties of hydrogels by preparing double‐network hydrogels, nanocomposite hydrogels, and nanostructured hydrogels. In this study, interpenetrating‐type dually‐crosslinked hydrogels were prepared via free radical crosslinking polymerization of acrylamide monomers in the presence of poly(aspartic acid) and subsequent immersion in a metal ion containing aqueous solution to induce extra physical crosslinking through ionic or coordination bonding. Using this approach, the mechanical properties of inherently weak and brittle homopolymer gels could be improved via interpenetrating the double network formed by both covalent bonding and metal coordination‐assisted reversible physical crosslinks. The preparation, swelling behavior, morphology, and mechanical properties of these hydrogels are presented. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45925.     

Improved mechanical strength of p(AAm) interpenetrating hydrogel network due to microgranular cellulose embedding

Here, polyacrylamide [p(AAm)]‐based hydrogels were synthesized via redox polymerization technique in the presence of various amounts of microgranular cellulose (MGCell) such as 0, 10, 25, 50, 100, and 150 mg MGCell/g. The synthesized p(AAm)‐MGCell interpenetrating hydrogels were characterized spectroscopically by FTIR, thermally by TGA analysis, and mechanically via dynamic mechanical measurements. Furthermore, the effect of the amount of MGCell in p(AAm) hydrogels on swelling% (S%) degree and mechanical strength was investigated. It was found that the S% was decreased from 727 ± 9 to 667 ± 6, 642 ± 8 and 619 ± 10, 568 ± 6 for p(AAm)‐MGCell interpenetrating network hydrogels containing 10, 50, 100, and 150 mg MGCell, respectively. On the other hand, the Young modulus of p(AAm)‐based hydrogels increased from 2.8 ± 0.2 kPa to 3.1 ± 0.03, 3.4 ± 0.1, 3.6 ± 0.3 and 4.3 ± 0.3 kPa with the incorporation of 10, 50, 100, and 150 mg MGCell into p(AAm) hydrogels. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44854.     

Mechanical Strengths of Hydrogels of Poly(N,N‐Dimethylacrylamide)/Alginate with IPN and of Poly(N,N‐Dimethylacrylamide)/Chitosan with Semi‐IPN Microstructures

Tough hydrogels receive continuous attention because of their promising applications in many fields. Herein, tough hydrogels of poly (N,N‐dimethylacrylamide) (PDMAA)/alginate (SA) are prepared, with interpenetrating network (IPN) and of PDMAA/chitosan (CS) with semi‐IPN microstructure, respectively. The toughening of the hydrogel by incorporating natural polymers is studied by compressing tests and dynamic mechanical analyses. Moreover, cyclic load–unload compressing of the two types of hydrogels are performed at low strains and under relatively high strains, in order to compare their strength and anti‐fatigue properties. The results indicate that the mechanical strength can be markedly improved upon addition of the natural polymers, and the IPN hydrogel of PDMAA/SA reveals much higher mechanical performances but is less stable. However, the semi‐IPN hydrogel of PDMAA/CS displays excellent anti‐fatigue stability, but with relatively low strength. Swelling tests, scanning electron microscopy, and Fourier transform infrared spectroscopy are carried out to study the microstructures of the hydrogels, which are carefully analyzed to understand the difference in mechanical performances of those hydrogels. The results suggest that the presence of sacrificial unit and higher chain density in the IPN are helpful for toughening hydrogels, while the semi‐IPN network is beneficial to improve the energy dissipation efficiency.     

Synthesis and evaluation of hyaluronic acid hydrogels modified with various crosslinkers as biodegradable polymers

Hyaluronic acid (HA), a high‐molecular‐weight natural polysaccharide, is often used in medical devices for regenerative medicine as it can undergo biodegradation via enzymatic action in the human body. HA exhibits both viscoelasticity and high biocompatibility and has therefore been used for ocular surgery. In particular, HA‐based hydrogels have been utilized as cell scaffold materials and devices in ophthalmological treatments. In this study, four hydrogels have been synthesized from HA derivatives with methacrylate groups and modified with crosslinkers such as adipic acid dihydrazide, divinyl sulfone, and dithiothreitol. Each of the synthesized hydrogels exhibits high transparency and strength as well as biodegradability in vitro. Hence, these HA‐based hydrogels demonstrate potential for applications as drug delivery systems and implants. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45453.     

Poly(2‐hydroxyethyl methacrylate) hydrogel: from a brittle material to a nanofilled semi‐interpenetrating polymer network with potential application in wound dressings

In this work we report the photopolymerization of poly(2‐hydroxyethyl methacrylate) (PHEMA) together with a hydrophilic chitosan derivate (carboxymethyl‐chitosan) to yield a semi‐interpenetrating polymer network (semi‐IPN) that was filled with poly(N‐vinylcaprolactam)/poly(ethylene glycol methacrylate) core–shell nanogels in order to enhance the mechanical properties of the resulting hydrogels. The mechanical properties of the nanofilled semi‐IPNs were found to be more suitable for wound dressing applications than the PHEMA hydrogel as described by dynamic mechanical analysis in dry form and submerged in water. This was evidenced by a higher Young's modulus and higher elongation at break in the semi‐IPNs compared to blank PHEMA hydrogels. Furthermore, when the hydrogels were filled with nanogels, there was an elongation at break similar to that of skin with only a slightly lower Young's modulus. © 2019 Society of Chemical Industry     

Preparation and antimicrobial activity of sulfopropyl chitosan in an ionic liquid aqueous solution

To improve the solubility and antibacterial activity of chitosan and expand its applications, we synthesized sulfopropyl chitosan (SP‐CS) with various degrees of substitution (DSs) under mild and green reaction conditions in the aqueous solution of an ionic liquid by a green process. The chemical structures of the polymers were verified by Fourier transform infrared spectroscopy and ¹H‐NMR, and the thermal stability was studied by thermogravimetric analysis. After modification, the water solubility of chitosan was improved significantly, and SP‐CS showed excellent solubility in water at neutral pH. The antibacterial activities of the SP‐CSs with various DSs were systematically studied for the first time by the Oxford cup method and optical density method. The results suggest that the antimicrobial properties of SP‐CS were enhanced by the introduction of sulfopropyl and increased with increasing DS. The application of chitosan could be expanded, and SP‐CS has the potential to be used as a water‐soluble antimicrobial. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44989.     

Synthesis and characteristics of the interpenetrating polymer network hydrogel composed of chitosan and polyallylamine

A temperature‐ and pH‐dependent hydrogel was studied with interpenetrating polymer network (IPN) hydrogels constructed with water‐insoluble chitosan and polyallylamine. Various IPNs were prepared from different weight ratios of chitosan–polyallylamine. Crosslinked‐IPN hydrogels exhibited relatively high equilibrium water content (EWC) in the range 80–83%. The EWC of IPN hydrogels depended on pH and the amount of complex, which is the content of chitosan and polyallylamine. The differential scanning calorimeter (DSC) thermogram of fully swollen IPN hydrogels appeared between 3 to 4 °C. The IPNs exhibited two glass‐transition temperatures (T_gs), indicating the presence of phase separation in the IPNs as exhibited by dielectric analysis (DEA). © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 498–503, 2002     

Preparation and property of starch nanoparticles reinforced aldehyde–hydrazide covalently crosslinked PNIPAM hydrogels

Injectable, de‐crosslinkable, and thermosensitive hydrogels are obtained by hydrazide‐functionalized poly(N‐isopropylacrylamide) and aldehyde‐functionalized dextrin through in situ crosslinked method. Natural based and degradable starch nanoparticles (SNPs) are used as fillers in order to improve mechanical property of hydrogels. Internal morphology, dynamic modulus, thermosensitivity property, de‐crosslinking performance, drug release, and in vitro cytotoxicity of hydrogels are investigated. Results show that SNPs disperse well throughout hydrogel and have no significant influence on gelation time and de‐crosslinking performance. Elasticity property of composite hydrogel prepared from 9.0 wt % precursors with 1.5 wt % fillers is improved significantly by SNPs and maximum storage modulus reaches 399.2 kPa, but 89.6 kPa of unreinforced hydrogels. Hydrogels exhibit good thermosensitive performance at alternating cyclic temperature of 25 and 37 °C. Doxorubicin hydrochloride‐loaded hydrogels can release more than 25 days. No significant cytotoxicity to L929 fibroblast cells is observed through a CCK‐8 assay for hydrogels, precursors, and SNPs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45761.     

Preparation and properties of crosslinked chitosan thermosensitive hydrogel for injectable drug delivery systems

The aim of this study was to prepare and investigate the physical properties of a thermosensitive crosslinked chitosan pregel solution, and evaluate the in vitro release profiles of macromolecules from this sol–gel transition system. Chitosan and poly (vinyl alcohol) were used to form an interpenetrating polymeric network with glutaraldehyde as the crosslinker, and glycerophosphate (GP) was added to transform the pH‐dependent solutions into thermosensitive pH‐dependent solutions. Rheological study showed that the gelation was dependent on the crosslink degree and GP concentration of the solution. The crosslinked gel had excellent mechanic properties and no apparent “pores” and formed an integrated hydrogel texture according to scanning electronic micrograph. Gas chromatography test guaranteed the medication safety with no detection of glutaraldehyde remnants in the hydrogels. In vitro release study showed that the gelation does not significantly affect the macromolecules diffusion but the crosslinking degree does. These results indicated that the hydrogel formed an intensified three‐dimensional hybrid network with interpenetrating molecules, which effectively buffered or delayed the macromolecules diffusion. The hydrogels sustained the drug release over 30 days and could be potentially used as in situ gelling implants. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1892–1898, 2006     

Characterization of hydrogels based on chitosan and copolymer of poly(dimethylsiloxane) and poly(vinyl alcohol)

Copolymers composed of poly(vinyl alcohol) (PVA) and poly(dimethylsiloxane) (PDMS) were crosslinked with chitosan to prepare semi‐interpenetrating polymer network (IPN) hydrogels by an ultraviolet (UV) irradiation method for application as potential biomedical materials. PVA/PDMS copolymer and chitosan was cast to prepare hydrogel films, followed by a subsequent crosslinking with 2,2‐dimethoxy‐2‐phenylacetophenone as a nontoxic photoinitiator by UV irradiation. Various semi‐interpenetrating polymer networks (semi‐IPNs) were prepared from different weight ratios of chitosan and the copolymer of PVA/PDMS. Photocrosslinked hydrogels exhibited an equilibrium water content (EWC) in the range of 65–95%. Swelling behaviors of these hydrogels were studied by immersion of the gels in various buffer solutions. Particularly, the PCN13 as the highest chitosan weight ratio in semi‐IPN hydrogels showed the highest EWC in time‐dependent and pH‐dependent swelling. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2591–2596, 2002     

Macroporous hydrogels based on chitosan derivatives: Preparation,characterization, and in vitro evaluation

Chitosan‐based hydrogels are considered as promising biomaterials for tissue engineering. Biological properties of chitosan could be significantly improved by modification of its chemical structure. This study was aimed at characterizing macroporous hydrogels fabricated by freeze‐drying technique from chitosan, which has been N‐acetylated by 2,2‐bis(hydroxymethyl)propionic acid or l ,d ‐lactide. The nature of the acetylated agent was shown to significantly affect hydrogels morphology, swelling behavior, zeta‐potential, and protein sorption as well as their degradation by lysozyme. According to scanning electron and confocal laser scanning microscopy, the hydrogels possessed interconnected macroporous network that facilitated cells penetration into the interior regions of the hydrogel. Chemical modification of chitosan significantly influenced L929 cell growth behavior on hydrogel compared to the non‐modified chitosan. The proposed chemical strategy for modification of chitosan could be considered as promising approach for improvement of chitosan hydrogels. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44651.     

Swelling and drug‐release behavior of the poly(AA‐co‐N‐vinyl pyrrolidone)/chitosan interpenetrating polymer network hydrogels

A series of novel hydrogels were prepared from acrylic acid (AA), N‐vinyl pyrrolidone (NVP), and chitosan by photopolymerization. The swelling behavior, gel strength, and drug release behavior of the poly(AA/NVP) copolymeric hydrogels and corresponding interpenetrating polymer network hydrogels were investigated. Results showed that the swelling ratios for the present hydrogels decreased with an increase of NVP content in the gel, but the gel strength increased with an increase of NVP content in the gel. Results also showed that the drug‐release behavior for the gels is related to the ionicity of drug and the swelling ratio of the gel. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2135–2142, 2004     

Studies on preparation and swelling properties of the N-isopropylacrylamide/chitosan semi-IPN and IPN hydrogels

Semi-interpenetrating network (semi-IPN) polymer gels and interpenetrating network (IPN) polymer gels with thermosensitivity were prepared by introducing a biodegradable polymer, chitosan, into the N-isopropyacrylamide (PNIPAAm) gel system. The swelling behavior, temperature sensitivity, pH sensitivity, gel strength, and drug-release behavior of PNIPAAm/chitosan semi-IPN and IPN hydrogels were investigated. The results indicated that the NIPAAm/chitosan semi-IPN and IPN hydrogels exhibited pH and temperature-sensitivity behavior and could slow drug release and diffusion from the gels. From the stress–strain curves of the hydrogels, the compression moduli of IPN gels containing crosslinked chitosan were higher than those of semi-IPN gels. This is because IPN gels have a more compact structure. The morphology of PNIPAAm/chitosan hydrogels was also investigated. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 2487–2496, 2001     

pH‐ and temperature‐responsive IPN hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate)

pH‐ and temperature‐responsive interpenetrating polymer network (IPN) hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate) were successfully prepared. The structure and properties of the hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and thermogravimetric analyzer. The equilibrium and dynamic swelling/deswelling behaviors and the drug release properties of the hydrogels responding to pH and/or temperature were also studied in detail. The hydrogels have the porous honeycomb structures, good miscibility and thermal stability, and good pH‐ and temperature‐responsivity. The volume phase transition temperature of the hydrogels is ca. 40°C. Changing the soy protein or crosslinker content could be used to control the swelling behavior and water retention, and the hydrogels have the fastest deswelling rate in pH 1.2 buffer solutions at 45°C. Bovine serum albumin release from the hydrogels has the good pH and temperature dependence. The results show that the proposed IPN hydrogels may have potential applications in the field of biomedical materials such as in drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39781.     

Swelling kinetics,mechanical properties,and release characteristics of chitosan‐based semi‐IPN hydrogels

Two series of pH‐sensitive semi‐interpenetrating network hydrogels (semi‐IPN) based on chitosan (CS) natural polymer and acrylamide (AAm) and/or N‐hydroxymethyl acrylamide (HMA) monomers by varying the monomer and CS ratios were synthesized by free radical chain polymerization. 5‐Fluorouracil (5‐FU), a model anticancer drug, has been added to the feed composition before the polymerization. The characterization of gels indicated that the drug is molecularly dispersed in the polymer matrix. The swelling kinetics of drug‐loaded gels have decreased with increased HMA content at 37°C in both distilled water and buffer solutions with a pH of 2.1 or 7.4. Elastic modulus of the gels increased with the increase in HMA content and higher CS concentration enhanced the elastic modulus positively. Moreover, cumulative release percentages of the gels for 5‐FU were ca. 10% higher in pH 2.1 than those in pH 7.4 media. It was determined that they can be suitable for the use in both gastric and colon environments. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41886.     

Swelling characterizations of chitosan and polyacrylonitrile semi‐interpenetrating polymer network hydrogels

Temperature‐ and pH‐responsive semi‐interpenetrating polymer network (semi‐IPN) hydrogels constructed with chitosan and polyacrylonitrile (PAN) were studied. The characterizations of semi‐IPN hydrogels were investigated using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). IPN hydrogels exhibited a relatively high swelling ratio, 23.31%–145.20% at room temperature. The swelling ratio of hydrogels depends on pH and temperature. DSC was used to determine the amount of free water in IPN hydrogels. The amount of free water increased with increasing chitosan content in the semi‐IPN hydrogels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 2011–2015, 2003     

Semi‐interpenetrating polymer network hydrogels based on aspen hemicellulose and chitosan: Effect of crosslinking sequence on hydrogel properties

Semi‐interpenetrating network hydrogel films were prepared using hemicellulose and chemically crosslinked chitosan. Hemicellulose was extracted from aspen by using a novel alkaline treatment and characterized by HPSEC, and consisted of a mixture of high and low molecular weight polymeric fractions. HPLC analysis of the acid hydrolysate of the hemicellulose showed that its major constituent sugar was xylose. X‐ray analysis showed that the relative crystallinity of hydrogels increased with increasing hemicellulose content up to 31.3%. Strong intermolecular interactions between chitosan and hemicellulose were evidenced by FT‐IR analysis. Quantitative analysis of free amino groups showed that hemicellulose could interrupt the chemical crosslinking of chitosan macromolecules. Mechanical testing and swelling experiments were used to define the effective network crosslink density and average molecular weight between crosslinks. Swelling ratios increased with increasing hemicellulose content and mainly consisted of H‐bonded bound water. Results revealed that by altering the hydrogel preparation steps and hemicellulose content, crosslink density and swelling behavior of semi‐IPN hydrogels could be controlled without deteriorating their mechanical properties. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

pH/temperature‐responsive semi‐IPN hydrogels composed of alginate and poly(N‐isopropylacrylamide)

Amino semitelechelic poly(N‐isopropylacrylamide) (PNIPAAm) was prepared by radical polymerization with aminoethanethiol hydrochloride as a chain‐transfer agent. Semi‐interpenetrating polymer network (semi‐IPN) hydrogels, composed of alginate and amine‐terminated PNIPAAm, were prepared by crosslinking with calcium chloride. From the swelling behaviors of semi‐IPNs at various pH's and Fourier transform infrared spectra at high temperatures, the formation of a polyelectrolyte complex was confirmed from the reaction between carboxyl groups in alginate and amino groups in modified PNIPAAm. Semi‐IPN hydrogels reached an equilibrium swelling state within 24 h. The water state in hydrogels, investigated by differential scanning calorimetry, showed that sample CAN55 [alginate/PNIPAAm (w/w) = 50/50] exhibited the lowest equilibrium water content and free water content among the hydrogels tested, which was attributed to its more compact structure compared to other samples and the high content of interchain bonding within the hydrogels. Alginate/PNIPAAm semi‐IPN hydrogels exhibited a reasonable sensitivity to the temperature, pH, and ionic strength of swelling medium. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1128–1139, 2002     

Preparation of alginate/poly(N‐isopropylacrylamide) semi‐interpenetrating and fully interpenetrating polymer network hydrogels with γ‐ray irradiation and their swelling behaviors

Semi‐interpenetrating polymer network (semi‐IPN) and fully interpenetrating polymer network (full‐IPN) hydrogels composed of alginate and poly(N‐isopropylacrylamide) were prepared with γ‐ray irradiation. The semi‐IPN hydrogels were prepared through the irradiation of a mixed solution composed of alginate and N‐isopropylacrylamide (NIPAAm) monomer to simultaneously achieve the polymerization and self‐crosslinking of NIPAAm. The full‐IPN hydrogels were formed through the immersion of the semi‐IPN film in a calcium‐ion solution. The results for the swelling and deswelling behaviors showed that the swelling ratio of semi‐IPN hydrogels was higher than that of full‐IPN hydrogels. A semi‐IPN hydrogel containing more alginate exhibited relatively rapid swelling and deswelling rates, whereas a full‐IPN hydrogel showed an adverse tendency. All the hydrogels with NIPAAm exhibited a change in the swelling ratio around 30–40°C, and full‐IPN hydrogels showed more sensitive and reversible behavior than semi‐IPN hydrogels under a stepwise stimulus. In addition, the swelling ratio of the hydrogels continuously increased with the pH values, and the swelling processes were proven to be repeatable with pH changes. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4439–4446, 2006