Recent advances in magnetic hydrogels

Smart hydrogels that respond to magnetic fields have attracted increasing interest in recent years. This is as a result of their numerous potential applications such as tunable delivery vehicles, magnetic resonance imaging contrast agents, hyperthermal therapy agents, etc. In this review, we summarize the methods for preparing magnetic hydrogels. Then we give an overview of magnetic hydrogels with various applications. Finally, the current limitations in the preparation and application of magnetic hydrogels are discussed and perspectives will be proposed for the next generation of hydrogels. © 2016 Society of Chemical Industry     

Synthesis and Evaluation of AlgNa-g-Poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead^® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.     

Hydrogels based on copolymers of 2‐hydroxyethylmethacrylate and 2‐hydroxyethylacrylate as a delivery system for proteins: Interactions with lysozyme

Hydrogels have attracted considerable attention due to numerous applications, in particular as contact lenses and carriers for sustained drug delivery. The aim of the present work is to characterize the interactions of copolymer hydrogels consisted of 2‐hydroxyethylmethacrylate (HEMA) and 2‐hydroxyethylacrylate (HEA) with a small protein (lysozyme) and to assess the potential applications of these hydrogels as a drug delivery system for sustained release of protein‐based therapeutics. Physicochemical properties of protein‐loaded hydrogels, as well as lysozyme in vitro loading and release and the conformation of the protein released from hydrogels were studied. The effect of copolymer composition on the protein deposition on hydrogels and protein aggregation in the presence of hydrogels was also assessed. The results show that introduction of HEA into the copolymeric hydrogels enhances their suitability as a delivery system for proteins. Copolymerisation of HEMA and HEA allows controlling the physicochemical properties of hydrogels and the protein release rate. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44768.     

Structure and relaxation in cellulose hydrogels

Cellulose‐based hydrogels show great potential for a wide range of applications. However, the structure of these hydrated gels is not fully understood. The impact of moisture on the structure and stability of cellulose based hydrogels is reported in this article. Analytical data based on GPC, NMR, and rheology are discussed. It was found that moisture‐induced gelation greatly reduces the crystallinity of the hydrogels, and the release of water from the hydrogels leads to permanent structural changes in the network structure due to the reformation of hydrogen bonding. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42071.     

Swelling characterization of the semiinterpenetrating polymer network hydrogels composed of chitosan and poly(diallyldimethylammonium chloride)

Temperature‐ and pH‐responsive semiinterpenetrating polymer network (SIPN) hydrogels, constructed with chitosan (CS) and poly(diallyldimethylammonium chloride) (PDADMAC), were studied. The characterizations of the IPN hydrogels were investigated by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and swelling tests, under various conditions. CS/PDADMAC SIPN hydrogels exhibited a relatively high swelling ratio, in the range of 248–462%, at 25°C. The swelling ratio of CS/PDADMAC IPN hydrogels are pH, temperature, and ionic concentration dependent. DSC was used for the quantitative determination of the amounts of freezing and nonfreezing water. The amount of free water increased with increasing PDADMAC content in the IPN hydrogels. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2876–2880, 2004     

Enhancement of bioactivity and bioavailability of curcumin with chitosan based materials

Curcumin (CUR) has been investigated for its poor accessibility to a site of action or absorption and rapid metabolism to cope with the limited medication and cure applications. This article reviews numerous approaches, such as encapsulated surfactant/polymeric micelles, liposomes, micro/nano-spheres, nano-suspensions/composites, nanocomplex, films, and hydrogels for effective transfer of CUR to target sites. Chitosan (CS), and chitosan derivatives have been found to enhance therapeutic efficacy of CUR. CS/modified-CS based alginate, cyclodextrin, starch, dextran sulfate, ZnO, phytosomes, and poly(butyl) cyanoacrylate drug delivery matrices improved bioavailability, prolonged drug loading and permeability, sustained release rate, improved solubility and stability (prevent metabolic degradation) of CUR, consequently promoting various clinical applications. CS based polysaccharide, protein, and metal oxide drug delivery nano formulations advantageously participated to improve biological activities of CUR. We have attempted to summarize these delivery approaches, and reviewed future trends/strategies to permit the introduction of CUR as practical therapeutic drug.     

Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems—State of Knowledge and Future Prospects

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.     

黄原胶水凝胶制备的研究进展

黄原胶水凝胶具有亲水性强、无毒、可降解及生物相容性好等优点,常作超吸水性树脂、药物载体和微胶囊。对黄原胶水凝胶的制备方法进行了综述,并对其发展进行展望。     

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.     

An In-depth Analysis of the Mechanical,Electrical, and Drug Release Properties of Gelatin–Starch Phase-Separated Hydrogels

Gelatin–starch-based phase-separated hydrogels were prepared in this study. Corn starch, soluble starch, and hydrated starch were used as the representative starches for the preparation of the hydrogels. Bright field microscopy suggested the formation of phase-separated hydrogels. An increase in the hydrophilic nature of the starch molecules resulted in decrease in the agglomeration of the starch particles within the gelatin matrices. Fourier transform infrared study confirmed the presence of starch particles within the hydrogels. X-ray diffraction studies suggested that the higher degree of crystallinity of corn starch and soluble starch was responsible for the comparative hydrophobic nature of these starch particles. Hydrated starch was found to be amorphous in nature and can be explained by the destruction of the intramolecular associative forces. Stress relaxation and creep recovery studies indicated predominant elastic nature of the hydrogels. Hydrated starch-containing hydrogels were firmer than corn starch and soluble starch because of the better miscibility of the hydrated starch particles within the gelatin matrices. The bulk resistance of the starch-containing hydrogels was higher. This was because of the capability of the starch particles to behave as dielectric medium. Incorporation of starch particles within the gelatin matrix was found to increase the polymer relaxation-mediated drug diffusion. Metronidazole-loaded hydrogels were found to have good antimicrobial activity.     

The Removal of Textile Dyes with Cross-Linked Chitosan-Poly(acrylamide) Adsorbent Hydrogels

This study examined the behaviors and mechanisms of chitosan (CS)-poly(acrylamide) (PAAM) full interpenetrating polymeric network (IPN) hydrogels as an adsorbent to remove EY-4GL and S-Blue textile dyes from an aqueous solution. CS-PAAM IPN hydrogels were prepared by acrylamide monomer polymerization in the presence of a natural polymer, e.g., chitosan. N,N′-methylenebisacrylamide (MBAM) and glutaraldehyde (GLA) were selected to cross-link PAAM and CS chains and a full-IPN structure formed simultaneously. Kinetic swelling studies of CS-PAAM IPNs were carried out with deionized water and aqueous dye solutions. The experimental data clearly suggested that the swelling process obeys second-order kinetics. Network and diffusion parameters for CS-PAAM and PAAM hydrogels were calculated and it was observed that these IPN hydrogels have high cross-linking efficiencies in comparison to PAAM hydrogels. Adsorption of textile dyes onto hydrogels was studied by a batch adsorption technique at 23°C and 40°C, and it was seen that the higher temperature increased the dye adsorption onto the hydrogels. L type (Lan gmuir) adsorption isotherms, according to Giles classification system, were established at the end of adsorption experiments. The prepared IPN hydrogels show good ability to uptake textile dyes from wastewater.     

Highly Stretchable,Compressible, Resilient,and Equilibrium Swelling Hydrogels with Elastic Nano Junctions

In this work, a flexible and polymerizable polyurethane‐urea (PUU) nanoparticle is used for the first time to prepare hydrogels showing highly stretchable, compressible, and resilient properties in their equilibrium swelling state. The PUU nanoparticles are prepared by reported interfacial polycondensation of O/W nanoemulsions followed by surface modification with acrylate groups. The hydrogels are prepared by simple free‐radical copolymerization of acrylamide and the polymerizable PUU nanoparticles. These PUU nanoparticles are expected to act as polyfunctional nanocrosslinkers and elastic junctions of the hydrogel’s network. The obtained hydrogels show high water containing character (94–97 wt%) in their equilibrium swelling state. The equilibrium swelling hydrogels can still be stretched and compressed up to 430–1170% and 95%, respectively, without fracture. Furthermore, cyclic tensile tests with a maximum strain of 500% or 700% show that the resilience of these equilibrium swelling hydrogels is as high as 95–97%. This work provides a new strategy and some new insights into the fabrication of fully swelling hydrogels with both extraordinary ductility and resilience, which is of critical importance for many of their practical applications.     

3D gel printing of magnetic hydrogel scaffolds assisted by in-situ gelation in a water level-controlled crosslinker bath

Polyvinylalcohol/chitosan (PVA/CS) is an excellent dual-network hydrogel material, but some significant challenges remain in fabricating composites with specific structures. In this study, 3D gel printing (3DGP) combined with a water-level controlled crosslinker bath was proposed for the rapid in-situ prototyping of PVA/CS/Fe₃O₄ magnetic hydrogel scaffolds. Specifically, the PVA/CS/Fe₃O₄ hydrogels were extruded into the crosslinker water to achieve rapid in-situ gelation, improving the printability of hydrogel scaffolds. The effect of the PVA/CS ratio on the rheological and mechanical properties of dual-network magnetic hydrogels was evaluated. The printing parameters were systematically optimized to facilitate the coordination between the crosslinking water bath and printer. The different crosslinking water baths were investigated to improve the printability of PVA/CS/Fe₃O₄ hydrogels. The results showed that the printability of the sodium hydroxide (NaOH) crosslinker was significantly better than that of sodium tripolyphosphate (TPP). The magnetic hydrogels (PVA: CS= 1: 1) crosslinked by NaOH had better compressive strength, swelling rate, and saturation magnetization of 1.17 MPa, 92.43%, and 22.19 emu/g, respectively. The MC3T3-E1 cell culture results showed that the PVA/CS/Fe₃O₄ scaffolds promoted cell adhesion and proliferation, and the scaffolds crosslinked by NaOH had superior cytocompatibility. 3DGP combined with a water-level controlled crosslinker bath offers a promising approach to preparing magnetic hydrogel materials.     

A comprehensive review of the polymer-based hydrogels with electrochemically synthesized silver nanoparticles for wound dressing applications

Modernization and improvement of wound dressing materials is an important topic in biomaterials and biomedicine fields, as the traditional materials are inadequate and susceptible to bacterial infections. In recent times, polymer-based hydrogel materials have presented themselves as excellent candidates for new-generation wound dressings with improved properties, such as high sorption ability, good mechanical properties, and low adhesiveness. Additionally, cross linked hydrogel matrices serve as excellent carriers for controlled release of antibacterial agents, such as silver nanoparticles (AgNPs), which are preferred over conventional antibiotics due to multi-phase mechanism of action and low susceptibility to induce bacterial resistance. Their incorporation inside polymer matrices allows improvement of wound dressing properties and sustained protection against bacterial infection. Electrochemical methods for AgNPs synthesis are facile and green alternatives to chemical routes, allowing the formation of highly stable AgNPs with strong antibacterial effect. In this article, we aim to provide a comprehensive review of the existing research on the topic of electrochemically synthesized silver nanoparticles incorporated in polymer matrices with a special focus on the chitosan-based hydrogels as prospective materials for wound dressing applications.     

Biomimetic protein‐based elastomeric hydrogels for biomedical applications

In recent years, protein‐based elastomeric hydrogels have gained increased research interest in biomedical applications for their remarkable self‐assembly behaviour, tunable 3D porous structure, high resilience (elasticity), fatigue lifetime (durability), water uptake, excellent biocompatibility and biological activity. The proteins and polypeptides can be derived naturally (animal or insect sources) or by recombinant (bacterial expression) routes and can be crosslinked via physical or chemical approaches to obtain elastomeric hydrogels. Here we review and present the recent accomplishments in the synthesis, fabrication and biomedical applications of protein‐based elastomeric hydrogels such as elastin, resilin, flagelliform spider silk and their derivatives. © 2013 Society of Chemical Industry     

Synthesis and properties of silver nanoparticles in chitosan‐based thermosensitive semi‐interpenetrating hydrogels

In this article, thermosensitive poly(N‐isopropyl acrylamide‐co‐vinyl pyrrolidone)/chitosan [P(NIPAM‐co‐NVP)/CS] semi‐interpenetrating (semi‐IPN) hydrogels were prepared by redox‐polymerization using N,N‐methylenebisacrylamide as crosslinker and ammonium persulfate/N,N,N′,N′‐tetramethylethylenediamine as initiator. Highly stable and uniformly distributed Ag nanoparticles were prepared by using the semihydrogel networks as templates via in situ reduction of silver nitrate in the presence of sodium borohydride as a reducing agent. Introduction of CS improves the hydrogels swelling ratio (SR) and stabilizes the formed Ag nanoparticles in networks. Scanning electron microscopy and transmission electron microscopy revealed that Ag nanoparticles were well dispersed with diameters of 10 nm. The semi‐IPN hydrogel/Ag composites had higher SR and thermal stability than its corresponding semi‐IPN hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Controllable properties and microstructure of hydrogels based on crosslinked poly(ethylene glycol) diacrylates with different molecular weights

This work describes a comprehensive study of hydrogels based on polyethylene glycol diacrylates (PEGDAs) with the molecular weight (MW) range of 400–2000. The blends of low‐ and high‐molecular weight PEGDA macromers with different ratios were photopolymerized under visible light irradiation, using a blue light sensitive photoinitiator Irgacure819, at the total polymer concentration of 60 wt %. Swelling ratios, wetting property, elastic moduli, transparency, and the microstructure of the resulting hydrogels were investigated. Among them, equilibrium water contents, hydrophilicity, and mesh size of the hydrogels increased while the elastic moduli decreased when increased the PEGDA MW or the content of higher MW PEGDA in the blends. Most of the hydrogels possessed excellent transparency in visible region. The viability of L929 cells on the surface of hydrogel was also estimated. All the selected hydrogels exhibited a relatively high proliferation rate, which demonstrated this hydrogel system with photoinitiator Irgacure819 had good biocompatibility. These results show the properties of PEGDA hydrogel could be easily adjusted by varying PEGDA MW or the ratios of low‐ and high‐MW macromers in the composites. It could be helpful for the design of proper PEGDA hydrogels in the applications as tissue engineering or drug delivery system. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

An Injectable Enzymatically Crosslinked and Mechanically Tunable Silk Fibroin/Chondroitin Sulfate Chondro-Inductive Hydrogel

An injectable hybrid hydrogel is synthesized, comprising silk fibroin (SF) and chondroitin sulfate (CS) through di-tyrosine formation bond of SF chains. CS and SF are reported with excellent biocompatibility as tissue engineering scaffolds. Nonetheless, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate articular cartilage. As CS is one of the cartilage extracellular matrix (ECM) components, it has the potential to enhance the biological activity of SF-based hydrogel in terms of cartilage repair. Therefore, altering the CS concentrations (i.e., 0 wt%, 0.25 wt%, 0.5 wt%, 1 wt%, and 2 wt%), which are interpenetrated between SF β-sheets and chains, can potentially adjust the physical, chemical, and mechanical features of these hybrid hydrogels. The formation of β-sheets by 30 days of immersion in de-ionized (DI) water can improve the compression strength of the SF/CS hybrid hydrogels in comparison with the same SF/CS hybrid hydrogels in the dried state. Biological investigation and observation depicts proper cell attachment, proliferation and cell viability for C28/I2 cells. Gene expression of sex-determining region YBox 9 (SOX9), Collagen II α1, and Aggrecan (AGG) exhibits positive C3H10T1/2 growth and expression of cartilage-specific genes in the 0.25 wt% and 0.5 wt% SF/CS hydrogels.     

Synthesis of multifunctional high strength,highly swellable,stretchable and self‐healable pH‐responsive ionic double network hydrogels

The multifunctional double network (DN) soft hydrogels reported here are highly swellable and stretchable pH‐responsive smart hydrogel materials with sufficient strength and self‐healing properties. Such multifunctional hydrogels are achieved using double crosslinking structures with multiple physical and chemical crosslinks. They consist of a copolymer network of acrylamide (AM) and sodium acrylate (Na‐AA) and other reversible network of poly(vinyl alcohol)–borax complex. They were characterized by Fourier transform IR analysis and studied for their hydrogen bonding and ionic interaction. The degree of equilibrium swelling was observed to be as high as 5959% (at pH 7.0) for a hydrogel with AM/Na‐AA = 25/75 wt% in the network (GS‐6 sample). The highest degree of swelling was observed to be 6494% at pH 8.5. The maximum tensile strength was measured to be 1670, 580 and 130 kPa for a DN hydrogel (GS‐2 sample: AM/Na‐AA =75/25 wt% with 20, 40 and 60 wt% water content, respectively). The self‐healing efficiency was estimated to be 69% for such a hydrogel. These multifunctional DN hydrogels with amalgamation of many functional properties are unique in hydrogel materials and such materials may find applications in sensors, actuators, smart windows and biomedical applications. © 2018 Society of Chemical Industry     

Insight into hydrogels

The development and introduction of injectable biomaterials and the identification of methods through which materials may form in situ are currently the topics of interest in materials science, specifically in the field of biomaterials. Over the last few decades, hydrogels which refers to the swellable polymeric matrices have gained wide attention due to their excellent characteristics such as swelling in different media, pH and temperature sensitivity, and sensitivity to other stimuli. Nowadays, injectable hydrogels have widely been studied due to their excellent insitu gelation at body temperature. These injectable insitu gels serve as depot system which ensures the local and systemic drug and gene delivery. These insitu gels also protect the proteins and peptide drugs invivo from environmental effect. The current review is made to report latest extensive literature regarding hydrogels, their classification, synthesis methods, structure of hydrogel network, methods of crosslinking, environment-sensitive hydrogel system, drug loading, and release, hydrogels as biosensors and applications of hydrogels.