Photopatterning of tough single-walled carbon nanotube composites in microfluidic channels and their application in gel-free separations

We report on the photopatterning of single carbon nanotube composites with soft hydrogel polymers in glass microchannels. Since the hydrogels by themselves are able to withstand liquid flow within the microchannels, we covalently combined them with single-walled carbon nanotubes to impart mechanical strength. We attempted this approach by patterning the gels within the microchannels without prior surface modifications. Our results show that the 1-cm nanocomposite hydrogels are far stronger than the free hydrogels. Moreover, the nanocomposites were able to concentrate and separate proteins within a 1.5-cm distance using gel-free buffers. The separation cannot only be tuned by changing the running buffer; the lack of gels in the running buffer reduces the chance of channel blockage and thus the lifetime of the device is prolonged. The usefulness of the patterned nanocomposites may be extended by a wide selection of nanocomposite properties and monomers to find a broad range of applications in lab-on-chip technology.     

Synthesis and Spatiotemporal Modification of Biocompatible and Stimuli‐Responsive Carboxymethyl Cellulose Hydrogels Using Thiol‐Norbornene Chemistry

Carboxymethyl cellulose (CMC) is functionalized with norbornene groups to undergo thiol‐norbornene cross‐linking reactions. Hydrogels synthesized from a single norbornene‐modified carboxymethyl cellulose (NorCMC) via a light‐initiated thiol‐ene cross‐linking reaction with a variety of dithiol cross‐linkers yield hydrogels with a tunable compression modulus ranging from 1.7 to 103 kPa. Additionally, thermoresponsiveness is spatiotemporally imparted to NorCMC hydrogels by photopatterning a dithiol‐terminated poly(N‐isopropyl acrylamide) cross‐linker, enabling swelling and topological control of the hydrogels as a function of incubation temperature. NorCMC hydrogels are cytocompatible as the viability of encapsulated human mesenchymal stem cells (hMSCs) is greater than 85% after 21 d while using a variety of cross‐linkers. Moreover, hMSCs can remodel, adhere, and spread in the NorCMC matrix cross‐linked with a matrix metalloproteinase‐degradable peptide, further demonstrating the utility of these materials as a tunable biomaterial.     

Physical alginate hydrogels based on hydrophobic or dual hydrophobic/ionic interactions: bead formation, structure, and stability

Hydrophobically associating alginate (AA) derivatives were prepared by covalent fixation of dodecyl or octadecyl chains onto the polysaccharide backbone (AA-C12/AA-C18). In semidilute solution, intermolecular hydrophobic interactions result in the formation of physical hydrogels, the physicochemical properties of which can be controlled through polymer concentration, hydrophobic chain content, and nonchaotropic salts such as sodium chloride. The mechanical properties of these hydrogels can then be reinforced by the addition of calcium chloride. The combination of both calcium bridges and intermolecular hydrophobic interactions leads to a decrease in the swelling ratio accompanied by an increase of elastic and viscous moduli. Beads made of hydrophobically modified alginate were obtained by dropping an aqueous solution of alginate derivative into a NaCl/CaCl2 solution. As compared to unmodified alginate beads, modified alginate particles proved to be stable in the presence of nongelling cations or calcium-sequestering agents. However, evidence is presented for a more heterogeneous structure than that of plain calcium alginate hydrogels with, in particular, an increase in the effective gel mesh size, as determined by partition and diffusion coefficient measurements.     

Self-assembled small molecular weight hydrogels of prodrugs

Prodrugs as building unit for construction of various hydrogelator in response to different stimulus (e.g., temperature, enzyme, pH value, ion).     

Rational Design of Heat‐Set and Specific‐Ion‐Responsive Supramolecular Hydrogels Based on the Hofmeister Effect

Smart supramolecular hydrogels have been prepared from a bolaamphiphilic L ‐valine derivative in aqueous solutions of different salts. The hydrogels respond selectively to different ions and are either reinforced or weakened. In one case, in contrast to conventional systems, the hydrogels are formed upon heating of the system. The use of the hydrogels in the controlled release of an entrapped dye is described as a proof of the potential applications of these systems. The responsive hydrogels were rationally designed by taking into account the noticeable effect of different ions from the Hofmeister series in the solubility of the hydrogelator, which was assessed by using NMR experiments. On the one hand, kosmotropic anions such as sulfate produce a remarkable solubility decrease in the gelator, which is associated with gel reinforcement, as measured by rheological experiments. On the other hand, chaotropic species such as perchlorate weaken the gel. A dramatic effect was observed in the presence of guanidinium chloride, which boosted the solubility of the gelator, in accordance with its chaotropic behaviour reported in protein science. In this case, a direct interaction of the guanidinium species with the carbonyl groups of the hydrogelator is detected by ¹³C NMR spectroscopy. The weakening of this interaction upon a temperature increase allows for the preparation of heat‐set hydrogelating systems.     

Characterization of Hydrogels Made of a Novel Spider Silk Protein eMaSp1s and Evaluation for 3D Printing

Recombinantly produced spider silk proteins have high potential for bioengineering and various biomedical applications because of their biocompatibility, biodegradability, and low immunogenicity. Here, the recently described small spider silk protein eMaSp1s is assembled into hydrogels, which can be 3D printed into scaffolds. Further, blending with a recombinantly produced MaSp2 derivative eADF4(C16) alters the mechanical properties of the resulting hydrogels. Different spider silk hydrogels also show a distinct recovery after a high shear stress deformation, exhibiting the tunability of their features for selected applications.     

Molecular Encryption and Reconfiguration for Remodeling of Dynamic Hydrogels

Dynamic materials have been widely studied for regulation of cell adhesion that is important to a variety of biological and biomedical applications. These materials can undergo changes mainly through one of the two mechanisms: ligand release in response to chemical, physical, or biological stimuli, and ligand burial in response to mechanical stretching or the change of electrical potential. This study demonstrates an encrypted ligand and a new hydrogel that are capable of inducing and inhibiting cell adhesion, which is controlled by molecular reconfiguration. The ligand initially exhibits an inert state; it can be reconfigured into active and inert states by using unblocking and recovering molecules in physiological conditions. Since molecular reconfiguration does not require the release of the ligand from the hydrogels, inhibiting and inducing cell adhesion on the hydrogels can be repeated for multiple cycles.     

Injectable Hyaluronic Acid Hydrogel Containing Platelet Derivatives for Synovial Fluid Viscosupplementation and Growth Factors Delivery

Osteoarthritisis a highly prevalent musculoskeletal disorder characterized by degradation of cartilage and synovial fluid (SF). Platelet derivatives as platelet-rich plasma (PRP) and platelet lysate have great potential in the treatment of osteoarthritis because they contain biologically active substances including growth factors (GFs). Rapid release of GFs and their short biological half-life are factors that can limit the therapeutic impact of PRP therapy. Herein, the first work that describes hydrogels based on polyaldehyde derivative of hyaluronic acid (HA-OX) as carriers of platelet derivatives for in situ applications is presented, which can be a possible solution to the problem. HA-OX hydrogels containing 50% (w/w) of PRP or platelet lysate can be injected using a syringe due to low viscosity(<10 Pa s) and injection force (<20 N), and reach elastic modulus up to 2000 Pa. Insulin-like GF-1 and Platelet-derived GF-AB release from HA-OX hydrogels (mesh size 297–406 nm) by Fickian and non-Fickian diffusion respectively. The released PRP GFs maintain their ability to induce cell proliferation (87%–92%). Based on the obtained results, the unique concept of a new material that can restore viscoelastic properties of SF and at the same time gradually deliver GFs from platelet derivatives is designed.     

Nanostructuration of soft hydrogels: synthesis and characterization of saccharidic methacrylate gels

With the tremendous development of biosensors, there is a strong need in new biocompatible materials avoiding possible denaturing of biological species, which can be easily processed with already existing technologies. The scope of this study was to develop new hydrogels which could be nanostructured by common lithographic methods. Therefore, new methacrylate hydrogels are described, which include functionalized monomers bearing either neutral groups, such as saccharidic moieties, anionic, or cationic groups. The gels have been synthesized by redox or photochemical-initiated radical polymerization. Their porosity has been characterized by thermoporometry, AFM, and electronic microscopy. The kinetics of the photocross-linking has been analyzed by piezorheometry on some of the materials and has been shown to be compatible with technological process time range. Although the obtained hydrogels are soft, their nanostructuration into 500-nm patterns could be performed by nanoimprint photolithography process, and these patterns were observed to be stable for several months.     

PAINT-ing Fluorenylmethoxycarbonyl (Fmoc)-Diphenylalanine Hydrogels

Self-assembly of fluorenylmethoxycarbonyl-protected diphenylalanine (FmocFF) in water is widely known to produce hydrogels. Typically, confocal microscopy is used to visualize such hydrogels under wet conditions, that is, without freezing or drying. However, key aspects of hydrogels like fiber diameter, network morphology and mesh size are sub-diffraction limited features and cannot be visualized effectively using this approach. In this work, we show that it is possible to image FmocFF hydrogels by Points Accumulation for Imaging in Nanoscale Topography (PAINT) in native conditions and without direct gel labelling. We demonstrate that the fiber network can be visualized with improved resolution (≈50 nm) both in 2D and 3D. Quantitative information is extracted such as mesh size and fiber diameter. This method can complement the existing characterization tools for hydrogels and provide useful information supporting the design of new materials.     

Immobilization of insulin-like growth factor-1 onto thermosensitive hydrogels to enhance cardiac progenitor cell survival and differentiation under ischemic conditions

Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions (low nutrient and oxygen) in the infarct hearts. Development of suitable cell carriers capable of supporting cell survival and differentiation under these harsh conditions is critical for improving the efficacy of current stem cell therapy. In this work, we created a family of novel cell carriers based on thermosensitive hydrogels and insulin-like growth factor 1 (IGF-1), and investigated if these cell carriers can improve cell survival and differentiation under ischemic conditions. The thermosensitive hydrogels were synthesized from N-isopropylacrylamide, acrylic acid, acrylic acid N-hydroxysuccinicimide ester, and 2-hydroxyethyl methacrylate-oligo(hydroxybutyrate). The hydrogel solutions can be readily injected through 26G needles, and can quickly solidify at 37 °C to form highly flexible hydrogels. IGF-1 was immobilized into the hydrogels in order to support long-term cell survival and differentiation. Different amount of IGF-1 was immobilized by using hydrogels with different content of N-hydroxysuccinicimide ester groups. Cardiosphere derived cells were encapsulated in the hydrogels and cultured under ischemic conditions. The results demonstrated that a significant improvement of cell survival and differentiation was achieved after IGF-1 immobilization. These IGF-1 immobilized hydrogels have the potential to improve cell survival and differentiation in infarct hearts.     

DNA-based supramolecular hydrogels: From construction strategies to biomedical applications

DNA-based supramolecular hydrogels are important and promising biomaterials for various applications due to their inherent biocompatibility and tunable physicochemical properties. The three-dimensional supramolecular matrix of DNA formed by non-covalently dynamic cross-linking provides exceptional adaptability, self-healing, injectable and responsive properties for hydrogels. In addition, DNA hydrogels are also ideal bio-scaffold materials owing to their tissue-like mechanics and intrinsic biological functions. Technically, DNA can assemble into supramolecular networks by pure complementary base pairing; it can also be combined with other building blocks to construct hybrid hydrogels. This review focuses on the development and construction strategies of DNA hydrogels. Assembly and synthesis methods, diverse responsiveness and biomedical applications are summarized. Finally, the challenges and prospects of DNA-based supramolecular hydrogels are discussed.     

The design,mechanism and biomedical application of self-healing hydrogels

Current advances made in self-healing hydrogels relating to the design strategies, self-healing mechanism, testing methods and biomedical application in vivo were extensively reviewed in this article.     

Birefringent hydrogels based on PAAm and lyotropic liquid crystal: Optical, morphological and hydrophilic characterization

In this work, hydrogels of polyacrylamide (or PAAm) with confined lyotropic liquid crystal (potassium laurate-decanol-water, KL-DeOH-H₂O) (or LLC) were synthesized. The hydrogels were characterized by polarized optical microscopy (POM), refractometry, optical transmission, scanning electron microscopy (SEM) and small angle X-ray scattering (SAXS). Besides these techniques, the hydrophilicity of hydrogels was characterized by the degree of swelling. Based on POM, it was observed that the texture of the birefringent hydrogels obtained depends on their cross-linking density, and that it is formed soon after hydrogel synthesis. Refractometry results indicated an behavior antagonist to that obtained for the system constituted by thermotropic liquid crystal inserted into the PAAm lattice in relation to the dependence of Δn on the AAm concentration and the optical transmittance. SEM micrographs show that birefringent hydrogels present rougher surface when compared to the surface of PAAm hydrogels. For the same AAm concentrations, it was observed that the hydrogels with confined LLC present larger swelling values (Q) when compared to those of PAAm hydrogels. The loss of water by birefringent hydrogels is twofold slower than that of PAAm hydrogels. Hydrogels formed by PAAm and lyotropic liquid crystal synthesized in this work can be potentially used in optical devices.     

Recent advances on hydrogels based on chitosan and alginate for the adsorption of dyes and metal ions from water

In contemporary times, water resources have become increasingly scarce and suffer from anthropogenic pollution sources with an organic and inorganic origin that are products of industrial, agricultural, and everyday waste. Contamination with heavy metals and dyes in wastewater is considered a risk for water sources that can leak into underground and surface sources, leading to increased biological and chemical contamination. The pollutant removal process is performed by adsorption treatment methods, which is the most common method, and it is considered an effective method with a high and economical removal rate.In this review, we discuss the use of biobased hydrogel adsorbents in the removal of organic dyes and metal ions from water. The literature indicates that hydrogels exhibit rapid absorption kinetics and a dye removal absorption capacity that can reach more than 100 mg/g and sometimes more than 2000 mg/g, with a metal adsorption capacity ranging from 38 mg/g to more than 440 mg/g. These results are discussed and compared by taking into account hydrogel materials that contain biopolymers such as alginate, chitosan or both. In general, absorption depends mainly on biobased materials, which have a natural origin and can be utilized to synthesize hydrogels to remove pollutants, dyes and heavy metals. Chitosan and alginate are prominent materials for this use and they can be incorporated with other components to obtain hydrogels or nanocomposite materials with different efficacies to remove dyes and metal ions.     

Polysaccharide-based supramolecular drug delivery systems mediated via host-guest interactions of cucurbiturils

With excellent biocompatibility and biodegradability,natural polysaccharides and their derivative s have exhibited great potential in constructing drug delivery ve hicles for tissue engineering and therapeutics.Cucurbit[n]uril(CB [n])-mediated reversible crosslinking of polysaccharides possess intrinsic stimuliresponsiveness towards competitive guests and have been extensively investigated to fabricate various particles and hydrogels for multiple stimuli-re sponsive drug release by incorpo ration with other stimuli including photo,redox,and enzyme.Through host-guest interactions between CB[6] and aliphatic diamines,functional tags covalently connected with CB[6] can be readily anchored into polysaccharidebased hydrogels,realizing multiple functionalization.The rheological prope rty and drug release profile of polysaccharide-based supramolecular hydrogels can be facilely tuned through CB [8]-mediated dyna mic homo or hetero crosslinking of polysaccharides and/or other polymers.In this review,we introduce and summarize recent progress regarding polysaccharide-based supramolecular drug delivery systems mediated via host-guest interactions of CB[6] and CB[8],covering both bulk hydrogels and particular systems.At the end,possible utilization of CB[7]-based host-guest interactions in constructing polysaccharide-based drug delivery systems and future perspectives of this research direction are also discussed.     

Photocrosslinking of Polyglycidol and Its Derivative: Route to Thermoresponsive Hydrogels

Hydrogels of biologically well‐tolerated, high‐molar‐mass polyglycidol (PGl) and its thermoresponsive derivative poly(glycidol‐co‐ethyl glycidyl carbamate) have been obtained by direct UV crosslinking in the solid state. Polymers with molar masses up to 1.45 × 10⁶ g mol⁻¹ were crosslinked in the presence of benzophenone or (4‐benzoylbenzyl)trimethylammonium chloride as photosensitizers. The photosensitizer concentration was varied from 2 to 10 wt%. The influence of polymer composition and photosensitizer type and amount on the crosslinking efficiency, swelling and temperature behavior of the obtained hydrogels was investigated. The photocrosslinking of PGl and poly(glycidol‐co‐ethyl glycidyl carbamate) led to hydrogels with swelling degrees up to 1700%. The swelling degrees of the hydrogels decreased with the increase of the environmental temperature indicating the thermoresponsive nature of gels. The swelling of obtained gels can be controlled by varying the composition of the copolymer precursor and by the network density.     

Simple,Rapid, and Large-Scale Fabrication of Multi-Branched Hydrogels Based on Viscous Fingering for Cell Culture Applications

Hydrogels are widely used in cell culture applications. For fabricating tissues and organs, it is essential to produce hydrogels with specific structures. For instance, multiple-branched hydrogels are desirable for the development of network architectures that resemble the biological vascular network. However, existing techniques are inefficient and time-consuming for this application. To address this issue, a simple, rapid, and large-scale fabrication method based on viscous fingering is proposed. This approach utilizes only two plates. To produce a thin solution, a high-viscosity solution is introduced into the space between the plates, and one of the plates is peeled off. During this procedure, the solution's high viscosity results in the formation of multi-branched structures. Using this strategy, 180 mm × 200 mm multi-branched Pluronic F-127 hydrogels are successfully fabricated within 1 min. These structures are used as sacrificial layers for the fabrication of polydimethylsiloxane channels for culturing human umbilical vein endothelial cells (HUVECs). Similarly, multi-branched Matrigel and calcium (Ca)-alginate hydrogel structures are fabricated, and HUVECs are successfully cultured inside the hydrogels. Also, the hydrogels are collected from the plate, while maintaining their structures. The proposed fabrication technique will contribute to the development of network architectures such as vascular structures in tissue engineering.     

Dependence of patterned binary alkanethiolate self-assembled monolayers on "UV-photopatterning" conditions and evolution with time, terminal group, and methylene chain length

We have investigated the mechanism of UV photopatterning of binary alkanethiolate self-assembled monolayers (SAMs) adsorbed on Au(111) using time-of-flight secondary ion mass spectrometry. The SAMs were photopatterned using a 500 W Hg arc lamp. The patterning process is strongly dependent on the wavelength of light used. When an unfiltered arc lamp is employed, IR light impinges on the sample and causes considerable sample heating. Methyl-terminated SAMs with less than 14 carbons in the chain melt at the temperatures reached and become very disordered and so can be easily displaced by a second SAM. This leads to significant pattern degradation ("erosion"). SAMs with greater than 14 carbons undergo a transition to an incommensurate phase but remain stable on the surface, and the pattern is retained. When the IR light is filtered out, a different behavior is observed. UV-photopatterned methyl-terminated SAMs with 10 carbons in the chain are stable. Terminal group interactions, such as H-bonding, provide extra stabilization energy during photopatterning, so some patterns with shorter carbon chains may also be stable. The displacement of the photooxidized SAMs on the patterned surface follows kinetics similar to that of large-area SAM formation.