Chemical Hydrogels Research Articles

Removing Polymeric Coatings With Nanostructured Fluids: Influence of Substrate, Nature of the Film, and Application Methodology

Cleaning is one of the most important and delicate operations in the conservation of cultural heritage, and, if not correctly performed, may irreversibly damage works of art. The removal of aged or detrimental polymeric coatings from works of art is a common operation in conservation, and nanostructured fluids (NSFs), such as aqueous swollen micelles and oil-in-water (o/w) microemulsions, are used as an alternative to non-confined organic solvents that pose a series of non-negligible drawbacks. NSFs effectiveness in removing polymeric coatings has been thoroughly demonstrated in the last decades, while their cleaning mechanism is still under investigation. The present work deepens the knowledge on the removal mechanisms of NSFs, studying the interaction of a four-component NSF with four different types of acrylic and vinyl polymer films cast from solutions or aqueous polymer latexes on three substrates (glass, marble and polystyrene) with different hydrophilicity and wettability. NSFs were applied either as non-confined or confined in cellulose poultices (traditionally employed by conservators), or in highly retentive chemical gels, observing the influence of the confining matrix on the removal process. It was found that the NSF/polymer film interaction is greatly dependent on the film structure and composition. Films formed from solvent solutions can be swollen by water/organic solvents mixtures or dewetted when a surfactant is added to the cleaning fluid; films formed from polymer latexes, on the other hand, are generally swollen even just by water alone, but poorly dewet. The substrate also plays an important role in the removal of polymer films formed from solutions, for instance the removal of an acrylic polymer from polystyrene could be achieved only through highly selective cleaning using NSF-loaded chemical hydrogels. These results can be key for conservators, providing innovative solutions to face new challenges in art preservation.

Poly-vinyl alcohol (PVA) crosslinked by trisodium trimetaphosphate (STMP) and sodium hexametaphosphate (SHMP): Effect of molecular weight, pH and phosphorylating agent on length of spacing arms, crosslinking density and water interaction

Abstract Poly-vinyl alcohol (PVA) with different molecular weight (27 kDa, 31 kDa, 61 kDa, 125 kDa and 195 kDa) were phosphorylated with trisodium trimetaphosphate (STMP) or sodium hexa-metaphosphate (SHMP) working at pH 10 or 12. Strong chemical hydrogels (G’>G”) were obtained starting from polymers with higher MW (61 kDa, 125 kDa and 195 kDa). Infrared Spectroscopy, UV Spectrophotometry and Rheological analyses indicated that crosslinking density is a function of a correct balance between deprotonation of polymeric chain, viscosity of the solution and length of the spacing arms. STMP and SHMP, as phosphorylating agent, behave differently changing pH and polymer MW. Crosslinked density was reflected in different capability to interact with water changing the ratio between freezable free water, freezable bound water and not freezable water.

Fabrication of Tough Hydrogel Composites from Photoresponsive Polymers to Show Double-Network Effect.

Inspired by the toughening mechanism of double-network (DN) gels, tough hydrogel composites with a sandwich structure were fabricated from photoresponsive polymers. By copolymerization of hydrophilic monomers, 2-ureidoethyl methacrylate (UM), and photoresponsive hydrophobic monomers, (2-nitrobenzyloxycarbonylaminoethyl methacrylate (NBOC)) at high concentrations, physical hydrogels that are soft and highly stretchable are formed due to the hydrophobic associations of NBOC, serving as dynamic crosslinkers. By UV irradiation, the physical crosslinking switches into chemical crosslinking, and the soft physical hydrogels transform into rigid and less stretchable chemical hydrogels. By UV curing the surface layers of the physical hydrogels, we prepared hydrogel composites having a sandwiched structure with two rigid outer layers and a soft inner layer. The molecular-level continuous interfaces and matched swelling ratios between the layers ensure the macroscale hydrogel composites' high strength and toughness with a DN gel effect. The outer layers fracture preferentially at deformation, playing a role like the first network of a DN gel, while the inner layer maintains the integrity, playing a role resembling the second network. The evolution of the fracture morphology of the rigid layers gives useful insight into the internal fracture process of DN gels.

A novel surface modification method upon halloysite nanotubes: A desirable cross-linking agent to construct hydrogels

Halloysite nanotubes (Hal), a kind of attractive natural one-dimensional nanomaterials, possess hollow tubular nanostructures, high aspect ratio and difference structures between external and internal surfaces. Hal show promising applications in various fields. A novel modification method was facilely achieved in this study via the click reaction between -CNO and –OH groups to functionalize vinyl groups onto the nanotubes, in which the product was carefully characterized by solid-state nuclear magnetic resonance (SSNMR), fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Then the modified Hal were used as cross-linking agent in the free radical copolymerization together with acrylamide (AM) to afford a uniform chemical hydrogel. The obtained hydrogel Hal-IM-AM showed good rheological property, low cytotoxicity and a much better absorption ability upon phosphorus than original Hal.

Strategies for Hyaluronic Acid-Based Hydrogel Design in Drug Delivery.

Hyaluronic acid (HA) is a natural, linear, endogenous polysaccharide that plays important physiological and biological roles in the human body. Nowadays, among biopolymers, HA is emerging as an appealing starting material for hydrogels design due to its biocompatibility, native biofunctionality, biodegradability, non-immunogenicity, and versatility. Since HA is not able to form gels alone, chemical modifications, covalent crosslinking, and gelling agents are always needed in order to obtain HA-based hydrogels. Therefore, in the last decade, different strategies for the design of physical and chemical HA hydrogels have been developed, such as click chemistry reactions, enzymatic and disulfide crosslinking, supramolecular assembly via inclusion complexation, and so on. HA-based hydrogels turn out to be versatile platforms, ranging from static to smart and stimuli-responsive systems, and for these reasons, they are widely investigated for biomedical applications like drug delivery, tissue engineering, regenerative medicine, cell therapy, and diagnostics. Furthermore, the overexpression of HA receptors on various tumor cells makes these platforms promising drug delivery systems for targeted cancer therapy. The aim of the present review is to highlight and discuss recent advances made in the last years on the design of chemical and physical HA-based hydrogels and their application for biomedical purposes, in particular, drug delivery. Notable attention is given to HA hydrogel-based drug delivery systems for targeted therapy of cancer and osteoarthritis.

TGF-β1-activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full-thickness hydrogel transplantation.

We showed previously that 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide hydrochloride (EDC) cross-linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers-bulky, aromatic N-cyclohexyl-N0-(2-morpholinoethyl)-carbodiimide (CMC), and nonbulky EDC-in a mouse corneal graft model. Murine corneas undergoing full-thickness implantation with these gels became opaque due to dense retro-corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c+ dendritic cells (DC) were found, suggesting a hydrogel-specific innate immune response. More DC infiltrated the stroma surrounding EDC-N-hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis-associated tenascin c expression. The opposite was true for CMC-NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor β1 (TGF-β1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF-β1 neutralisation. Furthermore, tenascin c staining was found in 40- to 50μm long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF-β1 alternatively activated (tolerising) DC regulate fibroblast-mediated tenascin c secretion, possibly via local production of TGF-β1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.

Disentangling Polymer Network and Hydration Water Dynamics in Polyhydroxyethyl Methacrylate Physical and Chemical Hydrogels

The cross-linker nature and water content may impact the microscopic dynamics of hydrogels components and thus their properties in applications such as drug delivery and water confinement. To inves...

POSS-Induced Dynamic Cross-Links Produced Self-Healing and Shape Memory Physical Hydrogels When Copolymerized with N-Isopropyl acrylamide.

The hydrogel morphology and viscoelasticity and the two-way shape memory behavior of copolymers of N-isopropyl acrylamide-polyhedral oligomeric silsesquioxane (PNIPAm-POSS) were investigated. NIPAm-POSS copolymers are unentangled and exhibit a thermoplastic and thermoresponsive hydrogel behavior ( Romo-Uribe ; ; Albanil , Eur. Polym. J. 2018 , 99 , 350 - 360 ). Here, we demonstrated by high-resolution transmission electron microscopy that POSS segregated into crystals to form physical cross-links. The hydrogels exhibited significant swelling, higher than chemical hydrogels at the same POSS content. The morphology of the hydrogels consisted of a honeycomb structure, and the pore size and swelling were a decreasing function of POSS. Moreover, the hydrogels were self-healing, exhibiting a liquid-like behavior under large amplitude shear and rubber-like behavior immediately after cessation of shear, that is, the POSS aggregates break and re-form, acting as dynamic cross-linkers. Strikingly, the physical networks behaved as perfect networks, thus matching chemically cross-linked networks and holding the scaling |η*| ∼ ω-1. Furthermore, the physical hydrogels exhibited a thermally activated shape memory (SM) behavior, without external stress and the lower critical solution temperature (LCST) being the only stimulus. The SM process involved swelling-deswelling, effectively opening opportunities for drug delivery. Furthermore, the SM was reversible, and no external stress was involved, therefore behaving as the two-way SM. Finally, POSS modulated the shear elastic modulus G' and LCST; therefore, the PNIPAm-POSS copolymers open opportunities for reusable, thermoformable SM hydrogels with tuned mechanical modulus and activation temperature.

Bottom-up design of hydrogels through click-chemistry modification of magnetic nanoparticles

The paper describes a modular approach based on click chemistry for the surface modification of magnetic oxide nanoparticles and their covalent inclusion within chemical hydrogels. As a proof of concept, we prepared cobalt ferrite nanoparticles and we modified their surfaces through the reaction with molecules bearing a carboxylic function and, alternatively, either an azide or an alkyne moiety. In the second step, the modified nanoparticles were reacted through a Huisgen 1,3-dipolar cycloaddition with a molecule bearing an unsaturated function and either an alkyne or an azide moiety, respectively. Finally, the particles were successfully copolymerized with acrylamide and N,N'-methylenebisacrylamide to obtain a magnetically responsive hydrogel. This approach could be easily extended towards any type of inorganic oxide nanoparticles and their inclusion within any radically co-polymerized hydrogel.

Chemical cross-linking methods for cell encapsulation in hydrogels

Cell-encapsulating hydrogels are of tremendous interest in regenerative medicine. Tissue engineering relies on biomaterials able to act as artificial extracellular matrices to guide cells towards the development of new tissues. Therefore, considerable efforts have been made to design biomaterials which mimic cells’ native environment, thus encouraging natural behavior. The choice of biomaterial in which cells are embedded is crucial for their survival, proliferation and differentiation. Being more stable, chemical hydrogels are preferred over physical hydrogels as cell-laden substrates. When designing chemical hydrogels, scientists must choose not only the nature of the network (synthetic and/or bio-polymers) but also the type of cross-link bridging hydrogel constituents. For that purpose, numerous chemistries have been used (i) to introduce reactive functions on the hydrogel precursors and (ii) to form covalent bonds in the presence of living cells. The review will discuss the advantages and limitations of each strategy.

Fingerprintable Hydrogel from Dual Reversible Cross-Linking Networks with Different Relaxation Times.

Most of the chemical hydrogels are stretchable, and deformed hydrogels may be recovered when the strain is removed. Such a hydrogel with viscoelastic property cannot be remolded under mild conditions. Here, we demonstrated that a combination of dual reversible cross-linking with different relaxation time scales could be used to develop a remoldable hydrogel responding to mild external stress. We fabricated the hydrogel with the surface-primary amine-rich silica nanodots (ca. 2.0 nm) and benzaldehyde-terminated poly(ethylene oxide)-poly(propylene oxide) (PPO)-poly(ethylene oxide) triblock copolymers (BAF127) at low temperature (<10 °C) to form the chemical cross-linking by Schiff-base bonding. Increasing temperature (>15 °C) induced the formation of physical cross-linking between the hydrophobic PPO segments. The latter network is weak and shows fast relaxation, whereas the former shows slow relaxation. The unique structural characteristics provides this hydrogel high stretchability and self-healability, as well as moldability. In particular, we demonstrated that this transparent hydrogel can keep the fine three-dimensional patterns of a fingerprint, which may be applied for collecting digital information of fingerprints for identification.

Supramolecular architectures of natural organic matter

A new conceptual model for supramolecular aggregation of natural organic matter (OM) is proposed. Scientific awareness of OM as natural hydrogels is slowly increasing although in the literature they are primarily categorized as physical hydrogels stabilized only by weak interactions. The supramolecular view of OM is here expanded, based on insight from comprehensive hydrogen bond theory, to include three-center–four-electron near-covalent linkages and introduce a new category of metachemical hydrogels that are neither chemical nor physical hydrogels. Hydrogels are typically classified into chemical (permanent, covalently bonded) or physical (reversible, ionic, hydrophobic, or hydrogen bonded) classes based on crosslinking. However, augmented by contemporary advances in hydrogen bonding theory purporting that not all hydrogen bonds are weak and that some hydrogen bonding motifs result in moderate and strong interactions, the popular supramolecular view of OM is extended to include all types of hydrogen bonds. We propose a new category of hydrogels exists—metachemical hydrogels—as a fundamental component of OM. Strong, near covalent, equally shared hydrogel cross-linkages in the metachemical hydrogel can outcompete water. Here, metachemical (≤1 μm diameter) and physical (>1 μm diameter) hydrogels are described as two primary forms of aggregates observed for OM in a hierarchical ‘supramolecular within supramolecular’ self-assembling architecture with new information about shear. The metachemical hydrogels are postulated to be encapsulated within a dispersible physical hydrogel scaffold which can form, dissipate, and spontaneously re-form over turbulent/quiescent cycles indicating reversible abiotic self-assembly. The significance of this investigation is to understand the form OM evolved in nature to provide essential functions. The potential for strong intermolecular forces to form a metachemical hydrogel in OM and the concept of a dynamic dual metachemical/physical hydrogel structure was not previously introduced. The metachemical hydrogel construct should inform hydrogen bonded systems in other chemical and biochemical disciplines.

Biocompatible chitosan-based hydrogel with tunable mechanical and physical properties formed at body temperature.

Chemical crosslinking hydrogels provide irreversible matrices with reliable characteristics for wider medical applications. When hydrogels used for hosting bioactive substances, matrices have to be crosslinked at mild condition with high yield reaction and inactive to the biological molecules. In this work, chitosan was functionalized with active double bonds as a precursor to hydrogel that gels at body temperature. Free-radical crosslinking was conducted in the presence of maleic anhydride (MA) and potassium persulfate (KPS). The chemical structures of hydrogels were confirmed via spectral analysis. Mechanical and gelation characteristics of the hydrogels were tuned by using different molar ratios of MA and KPS. Pores size was controlled according to the crosslinking density in range of 313-866 μm that agrees proportionally with the swelling degree. Young's modulus values were tuned to span from 6 to 31 Pa with opposite relationship with the stress at break that varied from 6 to 17 Pa. Hydrogel release profiles were plotted representing varied releasing rates. Gels were obtained at 37 °C for 2 h using KPS (24-48 mM) and different concentration of MA (0.17, 0.35 and 0.5 M). The tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT), colorimetric, biological assay using skin fibroblast cells showed high biocompatibility of chitosan-based hydrogels.

High-Performance Lignin-Based Water-Soluble Macromolecular Photoinitiator for the Fabrication of Hybrid Hydrogel

Developing low-migration macromolecular photoinitiators (macro PIs) is significant to achieve a sufficient biosafety for photopolymers. In this study, for the first time lignin was introduced into photoinitiating systems. A novel lignin-based water-soluble macro PI (L-PEG-2959) was designed and synthesized by introducing water-soluble PEG chain and photoinitiating moiety into lignin backbone simultaneously. A series of characterizations were performed, including 1H NMR, FTIR, UV–vis, GPC, and TGA analysis, which indicated that L-PEG-2959 has excellent light absorption property within 200–400 nm, high initiating efficiency, and superior water solubility. Additionally, L-PEG-2959 could be compatible well with glycidyl methacrylate-modified gelatin (Gel-GMA) and initiate the photopolymerization of Gel-GMA quickly under UV irradiation to form a chemical cross-linking hybrid hydrogel. Compared with the neat hydrogel prepared by Gel-GMA initiated with Irgacure2959, a commercial small molecular PI, the hybrid hy...

Release Behavior of Bovine Serum Albumin Loaded on Hydrogels of Natural Polymer Blend Poly (Vinyl Alcohol) and Analyze Their Compositions

Amylopectin AP, shellac SH, starch ST and ethyl cellulose EC, the natural polymers of multi functional groups have been blended with poly (vinyl alcohol). The new hydrogels were cross-linked chemically and physically using glutaraldehyde and sodium hexametaphosphate respectively. The prepared hydrogels and according to their different functional groups were studied for their degree of swelling in (pH4, pH7 and pH9) swelling medium and in saline solution of 0.1 N NaCl. The wt% of blend composite of the final hydrogels beside their degree of cross-link was manipulated for maximum loading and suitable release of BSA protein. FT-IR studies were used to improve blending of the mixed polymers in prepared hydrogels from their distinctive functional groups in the final hydrogels structures, as well as the emphasis on BSA protein loaded on prepared hydrogel. The XRD patterns have shown low crystalline structure of the prepared hydrogels after blending, with some elevation in degree of crystallinity for hydrogels cross-linked physically in comparison with hydrogels chemically cross-linked. The DTA thermograms have shown blending of polymers would change the thermal stability of the final hydrogels, and according to their Tg, Tcr and ∆H_f the hydrogels were thermally more stable in chemically cross-linked structures than cross-linked physically which because of their ionic interactions and their competition with hydrogen bonds. SEM micrographs have shown the homogeneous structures of the hydrogels after blending beside the irregular and fold surface for chemical cross-linked hydrogels which increase the surface area and increase the loading efficiency of some prepared hydrogels. Whereas physical cross-linked hydrogels have shown surface of smooth and uniform character with high porosity which increase the loading percentage too. The BSA protein model was depended for loading on prepared hydrogels, where the pH, time of loading and BSA concentrations have been shown a significant effects on maximum loading percentages. Finally, the cumulative release percentages R_cum of BSA protein from the prepared hydrogels were examined in different pH and temperatures of the release medium. The hydrogels after release the protein have shown morphological surface from SEM images filled with holes and remain stable where they can be used again.

Combining sol-gel and microfluidics processes for the synthesis of protein-containing hybrid microgels.

Biocompatible chemical cross-linked hybrid polyethylene glycol-based hydrogels were obtained from a sol-gel process using bis-silylated molecular precursors in biocompatible conditions. This soft procedure (pH = 7.4, at 25 °C), allows the production of microgels by microfluidics and easy encapsulation of a model protein (Bovin Serum Albumine, BSA).

Molecular Imprinting of Cyclodextrin Supramolecular Hydrogels Improves Drug Loading and Delivery.

Cyclodextrin-based controlled delivery materials have previously been developed for controlled release of different therapeutic drugs. In this study, a supramolecular hydrogel made from cyclodextrin-based macromonomers is subjected to molecular imprinting to investigate the impact on release kinetics and drug loading, when compared with non-imprinted, or alternately imprinted hydrogels. Mild synthesis conditions are used to molecularly imprint three antibiotics-novobiocin, rifampicin, and vancomycin-and to test two different hydrogel chemistries. The release profile and drug loading of the molecularly imprinted hydrogels are characterized using ultraviolet spectroscopy over a period of 35 days and compared to non-imprinted, and alternately imprinted hydrogels. While only modest differences are observed in the release rate of the antibiotics tested, a substantial difference is observed in the total drug-loading amount possible for hydrogels releasing drugs which has been templated by those drugs. Hydrogels releasing drugs which are templated by other drugs do not show improved release or loading. Analysis by FTIR does not show substantial incorporation of drug into the polymer. Lastly, bioactivity assays confirmed long-term stability and release of incorporated antibiotics.

Self-healing boronic acid-based hydrogels for 3D co-cultures.

Synthetic hydrogels have been widely adopted as well-defined matrices for three-dimensional (3D) cell culture, with increasing interest in systems that enable the co-culture of multiple cell types for probing both cell-matrix and cell-cell interactions in studies of tissue regeneration and disease. We hypothesized that the unique dynamic covalent chemistry of self-healing hydrogels could be harnessed for not only the encapsulation and culture of human cells but also the subsequent construction of layered hydrogels for 3D co-cultures. To test this, we formed hydrogels using boronic acid-functionalized polymers and demonstrated their self-healing in the presence of physiologically-relevant cell culture media. Two model human cell lines, MDA-MB-231 breast cancer cells and CCL151 pulmonary fibroblasts, were encapsulated within these dynamic materials, and good viability was observed over time. Finally, self-healing of cut hydrogel 'blocks' laden with these different cell types was used to create layered hydrogels for the generation of a dynamic co-culture system. This work demonstrates the utility of self-healing materials for multi-dimensional cultures and establishes approaches broadly useful for a variety of biological applications.

Further studies of a zinc-air cell employing a Zn-PCH (PVA chemical hydrogel) anode

The capacity utilization of zinc anode is usually very low in alkaline solution because of extreme dissolution and the passivation of zinc surface. This problem can be substantially overcome by using the composite electrode of Zn-PCH (PVA chemical hydrogel). In this work, PCH hydrogel film coated on the surface of the ZnO particles can reduce the solubility of the zinc and the concentration of the Zn(OH)42−. The cell with the Zn-PCH electrode reached 150 cycles before its capacity fell below 90% of the initial capacity, while the standard cell failed after 150 cycles. Based on the scanning electron microscopy observation of the Zn-PCH electrode, it shows a distribution of big spherical particles to form a loose and porous structure rather than a dense and compact film, which can help zinc electrode to stay in a loose and porous structure. Such texture is definitely in favor of the diffusion of OH− ions, facilitating the utilization of active material. Therefore, the Zn-PCH electrode can effectively improve the cycle performance of the secondary Zn-air battery.

Comparison of covalently and physically cross-linked collagen hydrogels on mediating vascular network formation for engineering adipose tissue

Timely tissue vascularization and integration of engineered tissues into a patient plays an important role in the successful translation of engineered tissues into clinically relevant therapies. To decrease the time needed to vascularize an engineered adipose tissue, suitable local microenvironments provided by hydrogels to support cell-based functional vascular network formation have been investigated. Using the same biomolecule in solution, two types of hydrogels can be obtained: a “physical hydrogel” which is thermal-induced self-assemble fibril initiation and growth, due to amino and carboxyl telopeptides on collagen chains, and a “chemical hydrogel” which results from the covalently cross-linking of the side chains induced by one step enzyme mediation in aqueous solution. In this paper, we compare the capability of engineering vascular network and large-sized vascularized adipose tissue in vivo in different types of collagen hydrogels, physical and chemical crosslinking. The relationships between vascular network formation and hydrogel properties for the two types of hydrogels are discussed. Finally, we successfully engineered a vascularized adipose tissue construct (∼877.6 adipocytes/mm2; 94% area of a construct) in the absence of exogenous cytokines in chemical covalently crosslinking cell-laden hydrogel. These results show manipulating the polymerized methods of a hydrogel could not only modulate vascular network formation, but also regenerate adipose tissue in vivo.