Design of temperature sensitive imprinted polymer hydrogels based on multiple-point hydrogen bonding

Weakly cross-linked temperature sensitive imprinted polymer hydrogels that recognize L-pyroglutamic acid (Pga) molecules via multiple-point hydrogen bonding were designed and synthesized. The amount of adsorption for Pga in imprinted hydrogels is 3-4 times higher than that in non-imprinted hydrogels. The selectivity test of imprinted polymer gels was carried out by using a series of structurally related compounds Pga, pyrrolidine, 2-pyrrolidone, L-proline as substrates. The results show that imprinted polymer gels exhibit high selectivity for Pga as compared to all the other tested substrates. The imprinted polymer hydrogels show good temperature sensitivity, special selectivity and reusability, suggesting that the polymer hydrogels would have an enormous potential for application in controlled drug release and separation field.     

Gel formation and photopolymerization during supramolecular self-assemblies of α-CDs with LA-PEG-LA copolymer end-capped with methacryloyl groups

A novel gelation occurs in water during supramolecular self-assemblies of α-cyclodextrins being threaded onto amphiphilic LA-PEG-LA copolymer end-capped with methacryloyl groups. The rheologic studies show that the gels are thixotropic and reversible. While exposed to UV irradiation with a photoinitiator added in advance, they can be photopolymerized in situ to give rise to chemically cross-linked biodegradable hydrogels with the markedly improved mechanical strength. The gels formed prior to and after UV irradiation are characterized using FTIR, ¹H NMR, WAXD and TGA techniques. The swelling ratio and in vitro degradation of the photocured hydrogels are also investigated. It appears that both physical and chemical gels have the potential to be used as injectable biomaterials.     

Physical, chemical, and chemical-physical double network of zwitterionic hydrogels

Zwitterionic hydrogels are very promising for biomedical applications. They are usually copolymerized with other polymers to improve their mechanical properties often at the expense of their biological properties. In this study, physically cross-linked poly(sulfobetaine methacrylate) (polySBMA) hydrogels were prepared, and their physical properties including phase behavior were investigated. Linear polySBMAs, with an average molecular weight ranging from 20.9 kDa to 316 kDa, were prepared via free radical polymerization at different KCl concentrations. The opaque-transparent phase transition of polySBMA-water mixtures were measured using a UV-vis spectrometer. Analysis from dynamic rheometry showed the formation of physically cross-linked hydrogels with mechanical ductility due to reversible charge interactions. Chemically cross-linked hydrogels were also prepared, and their swelling and mechanical properties were evaluated. It was found that the introduction of cross-linkers could lead to a decrease in the amount of physical cross-links in chemical hydrogels. In order to improve the mechanical properties of SBMA hydrogels, linear polySBMA was introduced to the network of chemically cross-linked polySBMA gels, creating a chemical-physical double network (DN) with both chemical and physical cross-links. The chemical-physical DN provides a desirable method to improve the mechanical properties of zwitterionic hydrogels without introducing other hydrophobic moieties.     

Physics of engineered protein hydrogels

Artificially engineered proteins and synthetic polypeptides have attracted widespread interest as building blocks for polymer hydrogels. The biophysical properties of the proteins, such as molecular recognition abilities, folded chain structures, and sequence-dependent thermodynamic behavior, enable advances in functional, responsive, and tunable gels. This review discusses the design of polymer hydrogels that incorporate protein domains, highlighting new challenges in polymer physics that are presented by this emerging class of materials. Five types of engineered protein hydrogels are discussed: (a) physically associating protein polymer gels, (b) amorphous artificially engineered protein networks, (c) engineered proteins with crystalline domains, (d) stretchable protein tertiary structures in gels, and (e) protein gels with biological recognition properties. The physics of the protein component and the physical properties of the resulting hydrogels are summarized, illustrating how advances in understanding these systems are leading to exciting novel biofunctional hydrogels. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013     

Stimuli-responsive nanocomposite gels

A new class of polymer hydrogels, nanocomposite hydrogels (NC gels), consisting of a unique organic (polymer)/inorganic (clay) network structure, was synthesized by in situ free-radical polymerization in the presence of exfoliated clay nanoparticles in an aqueous system. The resulting NC gels overcame most of the disadvantages associated with chemically cross-linked hydrogels, such as mechanical fragility, structural heterogeneity, and slow de-swelling rate. By using thermo-sensitive poly(N-isopropylacrylamide) (PNIPA) as a constituent polymer, NC gels with remarkable mechanical, optical, and swelling properties as well as thermo-sensitivity were obtained. The various properties of NC gels, such as transparency, gel volume, cell culturing, and surface friction changed significantly in response to the temperature and surrounding conditions. All the excellent properties and new stimuli-responsive characteristics of NC gels are attributed to the unique PNIPA/clay network structure. The thermo-sensitivities and the transition temperature can largely be controlled by varying the clay content and by the addition of solutes.     

Advanced Polymer Designs for Direct-Ink-Write 3D Printing

The rapid development of additive manufacturing techniques, also known as three-dimensional (3D) printing, is driving innovations in polymer chemistry, materials science, and engineering. Among current 3D printing techniques, direct ink writing (DIW) employs viscoelastic materials as inks, which are capable of constructing sophisticated 3D architectures at ambient conditions. In this perspective, polymer designs that meet the rheological requirements for direct ink writing are outlined and successful examples are summarized, which include the development of polymer micelles, co-assembled hydrogels, supramolecularly cross-linked systems, polymer liquids with microcrystalline domains, and hydrogels with dynamic covalent cross-links. Furthermore, advanced polymer designs that reinforce the mechanical properties of these 3D printing materials, as well as the integration of functional moieties to these materials are discussed to inspire new polymer designs for direct ink writing and broadly 3D printing.     

A review on tough and sticky hydrogels

In this review, we survey recent literature (2009–2013) on hydrogels that are mechanically tough and adhesive. The impact of published work and trends in the field are examined. We focus on design concepts, new materials, structures related to mechanical performance and adhesion properties. Besides hydrogels made of individual polymers, concepts developed to toughen hydrogels include interpenetrating and double networks, slide ring polymer gels, topological hydrogels, ionically cross-linked copolymer gels, nanocomposite polymer hydrogels, self-assembled microcomposite hydrogels, and combinations thereof. Hydrogels that are adhesive in addition to tough are also discussed. Adhesive properties, especially wet adhesion of hydrogels, are rare but needed for a variety of general technologies. Some of the most promising industrial applications are found in the areas of sensor and actuator technology, microfluidics, drug delivery and biomedical devices. The most recent accomplishments and creative approaches to making tough and sticky hydrogels are highlighted. This review concludes with perspectives for future directions, challenges and opportunities in a continuously changing world.     

Polymethacrylate Networks as Substrates for Cell Culture

Summary: methacrylate networks have a long history of applications in medical technology and much is known of their non-fouling properties. However, in recent times it has become clear that the swollen nature of these materials may provide some advantages if they are used as scaffolds in tissue engineering. In general however these hydrogels are resistant to protein adsorption and human cells do not easily adhere. In this work we provide an overview of several strategies that are designed to improve the cell-adhesive properties of hydrogels while maintaining their useful properties, mainly ease of diffusion of nutrients and growth factors. We describe our early attempts at modifying hydrogels based on 2,3-propandiol -1-methacrylate, with either hydrophobic units or acid groups. Modification with lauryl methacrylate produced an improvement but acid modification failed to provide surfaces that were conducive to cell culture. Much better scaffolds were prepared by amination of epoxy functional 2,3-propandiol-1-methacrylate networks. Optimized materials in this class were shown to be good substrates for the co-culture of bovine keratocytes with human corneal epithelial cells. We also describe the synthesis and biological properties of methacrylate conetworks, which phase separate during synthesis to give porous amphiphilic materials. Optimization of these materials produces materials that perform as well as tissue culture plastic so that confluent sheets of human dermal fibroblasts can be produced using standard culture techniques.     

Rapidly in situ forming biodegradable robust hydrogels by combining stereocomplexation and photopolymerization

Our previous studies have shown that stereocomplexed hydrogels can be rapidly formed in vitro as well as in vivo upon mixing aqueous solutions of eight-arm poly(ethylene glycol)-poly(l-lactide) (PEG-PLLA) and poly(ethylene glycol)-poly(d-lactide) (PEG-PDLA) star block copolymers. In this study, stereocomplexation and photopolymerization are combined to yield rapidly in situ forming robust hydrogels. Two types of methacrylate-functionalized PEG-PLLA and PEG-PDLA star block copolymers, PEG-PLLA-MA and PEG-PDLA-MA, which have methacrylate groups at the PLA chain ends and PEG-MA/PLLA and PEG-MA/PDLA, which have methacrylate groups at the PEG chain ends, were designed and prepared. Results showed that stereocomplexed hydrogels could be rapidly formed (within 1-2 min) in a polymer concentration range of 12.5-17.5% (w/v), in which the methacrylate group hardly interfered with the stereocomplexation. When subsequently photopolymerized, these hydrogels showed largely increased storage moduli as compared to the corresponding hydrogels that were cross-linked by stereocomplexation or photopolymerization only. Interestingly, the storage modulus of stereocomplexed-photopolymerized PEG-PLA-MA hydrogels increased linearly with increasing stereocomplexation equilibration time prior to photopolymerization (from ca. 6 to 32 kPa), indicating that stereocomplexation aids in photopolymerization. Importantly, photopolymerization of stereocomplexed hydrogels could take place at very low initiator concentrations (0.003 wt %). Swelling/degradation studies showed that combining stereocomplexation and photopolymerization yielded hydrogels with prolonged degradation times as compared to corresponding hydrogels cross-linked by photopolymerization only (3 vs 1.5 weeks). Stereocomplexed-photopolymerized PEG-MA/PLA hydrogels degraded much slower than corresponding PEG-PLA-MA hydrogels, with degradation times ranging from 7 to more than 16 weeks. Therefore, combining stereocomplexation and photopolymerization is a novel approach to obtain rapidly in situ forming robust hydrogels.     

Bioconjugating Thiols to Poly(acrylamide) Gels for Cell Culture Using Methylsulfonyl Co‐monomers

Poly(acrylamide) P(AAm) gels have become relevant model substrates to study cell response to the mechanical and biochemical properties of the cellular microenvironment. However, current bioconjugation strategies to functionalize P(AAm) gels, mainly using photoinduced arylazide coupling, show poor specificity and hinder conclusive studies of material properties and cellular responses. We describe methylsulfonyl‐containing P(AAm) hydrogels for cell culture. These gels allow easy, specific and functional covalent coupling of thiol containing bioligands in tunable concentrations under physiological conditions, while retaining the same swelling, porosity, cytocompatibility, and low protein adsorption of P(AAm) gels. These materials allow quantitative and standardized studies of cell‐materials interactions with P(AAm) gels.     

Dehydration of polymeric hydrogels designed for gelcasting method in ceramics

Key issue in the gelcasting method is the way water is released from the ceramic–hydrogel system. It is the first step to the formation of ceramic materials called green body. The purpose of the presented investigations is to establish the range of temperatures in which dehydration of the various hydrogels takes place, and at what temperatures the eight prepared hydrogels are disintegrated. The set of hydrogels polymers was obtained by radical polymerization from ionic and non-ionic monomers. The polymers were solved in water causing formation of clear gels. The dehydration and thermal decomposition of the obtained hydrogel samples was studied using thermal analysis techniques. The amount of water contained in hydrogels was determined as well as the temperature and products of polymer disintegration. Enthalpies of dewatering were also determined.     

Fluorescent Gold Nanoparticles: Synthesis of Composite Materials of Two‐Component Disulfide Gels and Gold Nanoparticles

Pseudoenantiomeric ethynylhelicene oligomers containing a disulfide group formed two‐component gels, which showed different solvent properties from gels without the disulfide group. The disulfide gels reacted with gold nanoparticles, and the resulting organic–inorganic composite materials exhibited fluorescence emission between 600–800 nm, along with emission from the oligomers at 450 nm. The disulfide gels and isolated gold nanoparticles loaded with the oligomers did not show the former emission. The 600–800 nm emission reversibly disappeared upon sol formation with heating, which was accompanied by an enhancement of the emission at 450 nm. The novel emission was also observed in the solid state.     

Novel Interpenetrating Networks (IPNs) Hydrogels Prepared In Situ by Liquid-Phase Photopolymerization

Novel interpenetrating networks (IPNs) hydrogels responsive to temperature were prepared in situ by liquid-phase photopolymerization. The first network of the IPNs (poly isopropyl acrylamide) were formed with a special kind of hectorite (Laponite XLS) modified by tetrasodium pyrophosphate as cross-linker and 2-oxogultaric acid as photoinitiator. The samples were subsequently immersed in an acrylamide (AAm) aqueous solution for at least one day for preparing IPNs hydrogels, in which acrylamide aqueous solution containing N,N′-Dimetyl acrylamide (MBAA) as cross-linker and 2-oxogultaric acid as photoinitiator. Then the second networks were in situ formed by introducing ultraviolet light irradiated PNIPAAm gels. The swelling/deswelling behaviors of IPNs hydrogels were measured. Compared with the corresponding nanocomposite PNIPAAm hydroges(NC hydrogels), chemically cross-linked PNIPAAm and PAAm IPNs hydrogels, the results indicate that the new IPN hydrogel has a faster deswelling rate above its LCST (≈32 °C). The effect was explained as being an additional contribution of the PAAm chains in IPN hydrogels, which may act as a water-releasing channel when the hydrophobic aggregation of PNIPA takes place.     

Alginate hydrogels as biomaterials

[Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation.     

Formation and transformations of polyelectrolyte gel-ampholyte dendrimer-surfactant ternary complexes

The reactions of complex gels formed via the sorption of a poly(propylenimine) ampholyte dendrimer of the fourth generation by oppositely charged lightly cross-linked polyelectrolyte hydrogels with ionogenic micelle-forming surfactants have been studied. The sorption of surfactant ions likely charged relative to the complexed ampholyte dendrimer by complex gels is associated with two parallel chemical reactions controlled by the concentration of the surfactant and pH which give rise to the formation of network-dendrimer-surfactant tertiary complexes. The reactions of complex gels with surfactant ions likely charged relative to the network polyelectrolyte make it possible at different solution pHs to prepare both negatively and positively charged hydrogels reinforced by disperse particles of the dendrimer-surfactant complex.     

Hydrophobically modified hydrogels containing azoaromatic cross-links: swelling properties, degradation in vivo and application in drug delivery

Hydrogels based on n-alkyl methacrylate esters (n-AMA) of various chain lengths, acrylic acid, and acrylamide cross-linked with 4,4-di(methacryloylamino)azobenzene were synthesized. The equilibrium swelling degree of the hydrogels in buffered solutions at pH 7.4 was shown to be very low in the pH range of the stomach. The entire swelling processes of the gels in the gastrointestinal tract were mainly dependent on those in the small intestine. In the buffered solution of pH 7.4 the diffusion of water into the gel slabs was discussed on the stress relaxation model of polymer chains. The results obtained are in good agreement with Schott's second-order diffusion kinetics. The biodegradability in vivo of their azobenzene cross-linking groups as well as the mechanism of degradation by cecal bacteria was studied. The gels are stable in the stomach but degradable by ananerobes present in the colon. The extent of degradation was considerably related to the equilibrium degree of swelling. The factors influencing the swelling degree were shown to influence the in vivo degradation of the gels. By changing these factors such as the degree of cross-linking, the length and content of the n-AMA side chains, it is possible to control both the degree of swelling and the degradation of the hydrogels.     

Simple one-step process for immobilization of biomolecules on polymer substrates based on surface-attached polymer networks

For the miniaturization of biological assays, especially for the fabrication of microarrays, immobilization of biomolecules at the surfaces of the chips is the decisive factor. Accordingly, a variety of binding techniques have been developed over the years to immobilize DNA or proteins onto such substrates. Most of them require rather complex fabrication processes and sophisticated surface chemistry. Here, a comparatively simple immobilization technique is presented, which is based on the local generation of small spots of surface attached polymer networks. Immobilization is achieved in a one-step procedure: probe molecules are mixed with a photoactive copolymer in aqueous buffer, spotted onto a solid support, and cross-linked as well as bound to the substrate during brief flood exposure to UV light. The described procedure permits spatially confined surface functionalization and allows reliable binding of biological species to conventional substrates such as glass microscope slides as well as various types of plastic substrates with comparable performance. The latter also permits immobilization on structured, thermoformed substrates resulting in an all-plastic biochip platform, which is simple and cheap and seems to be promising for a variety of microdiagnostic applications.     

Nanocomposite polymer hydrogels

The technological need for new and better soft materials as well as the drive for new knowledge and fundamental understanding has led to significant advances in the field of nanocomposite gels. A variety of complex gel structures with unique chemical, physical, and biological properties have been engineered or discovered at the nanoscale. The possibility to form self-assembled and supramolecular morphologies makes organic polymers and inorganic nanoparticles desirable building blocks for the design of water based gels. In this review, we highlight the most recent (2004–2008) accomplishments and trends in the field of nanocomposite polymer hydrogels with a focus on creative approaches to generating structures, properties, and function within mostly biotechnological applications. We examine the impact of published work and conclude with an outline on future directions and challenges that come with the design and engineering of new nanocomposite gels.     

Hybrid Hydrogels Assembled from Phenylalanine Derivatives and Agarose with Enhanced Mechanical Strength

A roadblock for supramolecular hydrogels is their poor mechanical properties. Herein, to enhance the mechanical strength of supramolecular hydrogels, agarose(AG) was incorporated into the low molecular weight hydrogelator(G1). The results of scanning electron microscopy(SEM), circular dichroism(CD) and Fourier transform infrared spectroscopy(FTIR) prove that G1 gelators can self-assemble into cross-linked network together with AG. The mechanical properties of the gels are characterized by a rotary rheometer and the mechanical properties of the hybrid hydrogels(Hgel) can be significantly improved and may be further tuned by changing the ratio of the two components. For example, the elastic modulus of Hgel Ⅱ[m(G1):m(AG)=7:3] is about 2 times higher than that of G1 hydrogel. The results demonstrate that the mechanical property of hybrid supramolecular hydrogels can be adjusted through the formation of a cross-linked network.     

Intelligent Hydrogels Via Gamma-Ray Induced Polymerization of Micellar Monomer Solutions and Microemulsions

Summary: Intelligent hydrogels were prepared upon polymerization of micellar aqueous comonomer solutions and microemulsions containing the cationic surfactant monomer 11-acryloyloxyundecyltrimethylammonium bromide (AUTMAB) and N-isopropylacrylamide (NIPAM). A chemically and physically cross-linked network structure is formed consisting of blocks of P-NIPAM and P-AUTMAB. The P-AUTMAB blocks act as physical cross-linking units improving the mechanical stability of the gel. While pure P-NIPAM hydrogels are disrupted under low compression, gels polymerized from micellar solution or microemulsion can be reversibly compressed. The presence of AUTMAB in the gel increases the swelling up to a factor of 30 compared with the pure P-NIPAM gel. Rapid and reversible swelling is observed for hydrogels with an AUTMAB content up to 2.5 wt.-%.