Hydrogel Architecture Research Articles

High-performance solar-driven interfacial evaporation through molecular design of antibacterial, biomass-derived hydrogels

Hydrogel has been regarded as one of the most promising candidates for next-generation solar evaporation technology to produce freshwater from non-potable water. However, synthesizing hydrogel absorbers that can precisely regulate water state and significantly reduce the water vaporization enthalpy remains a grand challenge. Herein, we report the rational design of a novel hydrogel hybrid solar evaporator constructed by poly(vinyl alcohol) and sodium lignosulfonate (SLS), with addition of carbon nanotube as a light absorption material. The abundant sulfonate and hydroxyl groups of SLS enhance the interplay between hydrogel and water molecule through electrostatic interaction and hydrogen bond. As such, the presence of SLS not only remarkably promotes the hydrophilicity and water transport of hydrogel, but also precisely tunes the state of water molecule and the content of intermediate water for reducing the water vaporization enthalpy. The combined advantageous features endow the as-prepared hydrogel with an evaporation rate up to 2.09 kg m−2 h−1 under 1 Sun illumination, along with good anti-acid/basic abilities, antibacterial property, high salt-tolerance, and self-cleaning capability in purifying different types of wastewater. Finally, an outdoor solar seawater desalination device is designed to generate drinking water from seawater. The daily drinking water production amount per square meter is ca. 13 kg, which satifies the five adults' daily water consumption (12.5 kg). The present study highlights that rationally constructing the molecular architecture of hydrogel and tuning the interplay between water and hydrogel are effective strategies to fabricate advanced hydrogel solar evaporators for addressing the global freshwater shortage.

Physically Cross-Linked Hyaluronan-Based Ultrasoft Cryogel Prepared by Freeze-Thaw Technique as a Barrier for Prevention of Postoperative Adhesions.

Postsurgical peritoneal adhesions are a common and serious postoperative complication after various peritoneal surgeries, such as pelvic and abdominal surgery. Various studies have shown that peritoneal adhesions can be minimized or prevented by physical anti-adhesion barriers, including membranes, knits, and hydrogels. Hydrogels have attracted great attention in preventing peritoneal adhesions because the dimensional architecture of hydrogels is similar to that of the native extracellular matrix. However, chemical cross-linkers had to be used in the preparation of chemical hydrogels, which may have problems in cytotoxicity or unwanted side effects. This fact prompts us to create alternative cross-linking methods for the development of biocompatible hydrogels as physical barriers. Herein, we report a physically cross-linked flexible hyaluronan (HA) cryogel prepared via a freeze-thaw technique as a novel anti-adhesion biomaterial for completely preventing postsurgical peritoneal adhesions. In vitro studies demonstrated that this physically cross-linked HA cryogel exhibited excellent biocompatibility, the inherently desirable biocompatibility and functionality of HA being integrally retained as much as possible. Intriguingly, the rheological properties and appropriate biodegradability of the cryogels were readily tailored and tunable by way of the gelation process. In vivo assessments suggested that the cryogel, as a physical barrier, satisfactorily prevented fibroblast penetration and attachment between the injured tissues and nearby normal organs. Furthermore, the molecular mechanism studies revealed that the HA cryogel could prevent peritoneal adhesion by inhibiting inflammatory response and modulation of the fibrinolytic system. Our results show that HA ultrasoft cryogel is a promising clinical candidate for prolonged adhesion prevention.

Carboxyalkylchitosan-based hydrogels with “imine clip”: Enhanced stability and amino acids-induced disassembly under physiological conditions

Here we report on the properties of hydrogels of carboxyalkylchitosans-salicylimines depending on the salicylaldehyde (SA) grafting density, type of carboxyalkyl substitution, pH, and presence of amino acids. The mechanism of SA grafting has been investigated using 13C NMR and FT-IR spectroscopy and elemental analysis. We have found that, despite lower SA grafting density to carboxyalkylchitosans, gelation in these solutions occurred at much lower SA:polymer molar ratios than for chitosan-salicylimines, being the highest for a N-carboxyethylchitosan with a medium substitution degree. Controlled disassembly of supramolecular architecture of hydrogel of N-carboxyethylchitosan-salicylimine at physiological pH was achieved via the transimination reaction in the presence of amino acids with the efficiency decreased in the order: lysine > arginine ≥ serine. Application of carboxyalkylchitosans opens a new window for development of salicylimine-based hydrogels with lower SA grafting density, better mechanical properties, and reversibility in a broader pH range than it was earlier known for chitosan-based biodynamers.

RGD-pectin microfiber patches for guiding muscle tissue regeneration.

Opportunely arranged microscaled fibers offer an attractive 3D architecture for tissue regeneration as they may enhance and stimulate specific tissue regrowth. Among different scaffolding options, encapsulating cells in degradable hydrogel microfibers appears as particularly attractive strategy. Hydrogel patches, in fact, offer a highly hydrated environment, allow easy incorporation of biologically active molecules, and can easily adapt to implantation site. In addition, microfiber architecture is intrinsically porous and can improve mass transport, vascularization, and cell survival after grafting. Anionic polysaccharides, as pectin or the more popular alginate, represent a particularly promising choice for the fabrication of cell-laden patches, due to their extremely mild gelation in the presence of divalent ions and widely accepted biocompatibility. In this study, to combine the favorable properties of hydrogel and fibrous architecture, a simple coaxial flow wet-spinning system was used to prepare cell-laden, 3D fibrous patches using RGD-modified pectin. Rapid fabrication of coherent self-standing patches, with diameter in the range of 100-200 μm and high cell density, was possible by accurate choice of pectin and calcium ions concentrations. Cells were homogeneously dispersed throughout the microfibers and remained highly viable for up to 2 weeks, when the initial stage of myotubes formation was observed. Modified-pectin microfibers appear as promising scaffold to support muscle tissue regeneration, due to their inherent porosity, the favorable cell-material interaction, and the possibility to guide cell alignment toward a functional tissue.

High throughput screening of fiber-based adsorbents for material and process development

There has been a growing interest in fibers and fiber-based adsorbents as alternative adsorbents for preparative chromatography. While the benefits of fiber-based adsorbents in terms of productivity have been highlighted in several recent studies, microscale tools that enable a fast characterization of these novel adsorbents, and an easy integration into process development workflows, are still lacking.In the present study an automated high-throughput screening (HTS) for fiber-based adsorbents was established on a robotic liquid handling station in 96 well filter plates. Two techniques – punching and weighing – were identified as techniques that enabled accurate and reproducible portioning of short-cut fiber-based adsorbents. The impact of several screening parameters such as phase ratio, shaking frequency, and incubation time were investigated and optimized for different types of fiber-based adsorbents. The data from the developed HTS correlated with data from packed fiber columns, and binding capacities from both scales matched closely. Subsequently, the developed HTS was utilized to optimize the hydrogel architecture of anion exchange (AEX) fiber-based adsorbent prototypes. A novel AEX fiber-based adsorbent was developed that compared favorably with existing resin and membrane adsorbents in terms of productivity and DNA binding capacity. In addition, the developed HTS was also successfully employed in order to identify step elution conditions for the purification of a monoclonal antibody from product- and process-related impurities with a cation exchange (CEX) fiber-based adsorbent. Trends from the HTS were found to be in good agreement with trends from lab scale column runs.The tool developed in this paper will enable a faster and more complete characterization of fiber-based adsorbents, easier tailoring of such adsorbents towards specific process applications, and an easier integration of such materials into processes. In comparison to previous lab scale experiments, material requirements are reduced by a factor of 3–40 and time requirements are reduced by a factor of 2–5.

Improved glucose oxidation catalytic current generation by an FAD-dependent glucose dehydrogenase-modified hydrogel electrode, in accordance with the Hofmeister effect

Herein, we describe the effect of varying anions in an electrolyte solution on current generation by a redox hydrogel electrode. The electrode surface is coated with a thin film of hydrogel matrix, consisting of an osmium (Os) redox polymer including tethered Os complexes, polymer backbone, and a redox enzyme. In this case, the enzymes employed are flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH), which catalyzes glucose oxidation, and the result was compared with that reported earlier for glucose oxidase (GOx). The hydrogel matrix facilitates efficient electron transfer from glucose to the electrode via collision of the Os complexes and thus acts as a mediator. The degree of impact of anions on current generation is characteristic of the Hofmeister series. Chaotropic anions, such as nitrate and chloride, increase and decrease the catalytic current produced by FAD-GDH and GOx hydrogel electrodes, respectively. Such anions can adsorb onto the cationic region of the FAD-GDH surface and induce a negative charge, which enhances electrostatic interactions between the enzyme and the positively charged Os polymer. Kosmotropic anions, such as sulphate and phosphate increase the catalytic current due to hydrogel shrinkage, which increases the relative concentrations of both enzyme and mediator within the hydrogel architecture due to an increase in density. High-performance electrode design depends on understanding the impact of ion identity on catalytic current responses of redox hydrogel electrodes.

Strong tough hydrogels via the synergy of freeze-casting and salting out

Natural load-bearing materials such as tendons have a high water content of about 70 per cent but are still strong and tough, even when used for over one million cycles per year, owing to the hierarchical assembly of anisotropic structures across multiple length scales1. Synthetic hydrogels have been created using methods such as electro-spinning2, extrusion3, compositing4,5, freeze-casting6,7, self-assembly8 and mechanical stretching9,10 for improved mechanical performance. However, in contrast to tendons, many hydrogels with the same high water content do not show high strength, toughness or fatigue resistance. Here we present a strategy to produce a multi-length-scale hierarchical hydrogel architecture using a freezing-assisted salting-out treatment. The produced poly(vinyl alcohol) hydrogels are highly anisotropic, comprising micrometre-scale honeycomb-like pore walls, which in turn comprise interconnected nanofibril meshes. These hydrogels have a water content of 70-95 per cent and properties that compare favourably to those of other tough hydrogels and even natural tendons; for example, an ultimate stress of 23.5±2.7 megapascals, strain levels of 2,900±450 per cent, toughness of 210±13 megajoules per cubic metre, fracture energy of 170±8 kilojoules per square metre and a fatigue threshold of 10.5±1.3 kilojoules per square metre. The presented strategy is generalizable to other polymers, and could expand the applicability of structural hydrogels to conditions involving more demanding mechanical loading.

Projection Microstereolithographic Microbial Bioprinting for Engineered Biofilms.

Microbes are critical drivers of all ecosystems and many biogeochemical processes, yet little is known about how the three-dimensional (3D) organization of these dynamic organisms contributes to their overall function. To probe how biofilm structure affects microbial activity, we developed a technique for patterning microbes in 3D geometries using projection stereolithography to bioprint microbes within hydrogel architectures. Bacteria were printed and monitored for biomass accumulation, demonstrating postprint viability of cells using this technique. We verified our ability to integrate biological and geometric complexity by fabricating a printed biofilm with two E. coli strains expressing different fluorescence. Finally, we examined the target application of microbial absorption of metal ions to investigate geometric effects on both the metal sequestration efficiency and the uranium sensing capability of patterned engineered Caulobacter crescentus strains. This work represents the first demonstration of the stereolithographic printing of microbials and presents opportunities for future work of engineered biofilms and other complex 3D structured cultures.

Synergistic control of mechanics and microarchitecture of 3D bioactive hydrogel platform to promote the regenerative potential of engineered hepatic tissue

Culturing autologous cells with therapeutic potential derived from a patient within a bioactive scaffold to induce functioning tissue formation is considered the ideal methodology towards realizing patient-specific regenerative medicine. Hydrogels are often employed as the scaffold material for this purpose mainly for their tunable mechanical and diffusional properties as well as presenting cell-responsive moieties. Herein, a two-fold strategy was employed to control the physicomechanical properties and microarchitecture of hydrogels to maximize the efficacy of engineered hepatic tissues. First, a hydrophilic polymeric crosslinker with a tunable degree of reactive functional groups was employed to control the mechanical properties in a wide range while minimizing the change in diffusional properties. Second, photolithography technique was utilized to introduce microchannels into hydrogels to overcome the critical diffusional limit of bulk hydrogels. Encapsulating hepatic progenitor cells derived via direct reprogramming of tissue-harvested fibroblasts, the application of this strategy to control the mechanics, diffusion, and architecture of hydrogels in a combinatorial manner could allow the optimization of their hepatic functions. The regenerative capacity of this engineered hepatic tissue was further demonstrated using an in vivo acute liver injury model.

Wood-Derived Hydrogels as a Platform for Drug-Release Systems.

Wood (cellulose and lignin)-based hydrogels were successfully produced as platforms for drug-release systems. Viscoelastic and cross-linking behaviors of precursor solutions were tuned to produce highly porous hydrogel architectures via freeze-drying. Pore sizes in the range of 100–160 μm were obtained. Varying lignin molecular structure played a key role in tailoring swelling and mechanical performance of these gels with organosolv-type lignin showing optimum properties due to its propensity for intermolecular cross-linking, achieving a compressive modulus around 11 kPa. Paracetamol was selected as a standard drug for release tests and its release rate was improved with the presence of lignin (50% more compared to pure cellulose hydrogels). This was attributed to a reduction in molecular interactions between paracetamol and cellulose. These results highlight the potential for the valorization of lignin as a platform for drug-release systems.

Looking inside Poly(N-isopropylacrylamide) Microgels: Nanomechanics and Dynamics at Solid–Liquid Interfaces

The continuous improvement of synthesis leads to a great variety in the internal architecture and functionality of colloidal hydrogels. A majority of envisioned applications use microgels as colloi...

Characterizing the Molecular Architecture of Hydrogels and Crosslinked Polymer Networks beyond Flory-Rehner-I. Theory.

In the early 1940s, Paul Flory and John Rehner published a series of papers on the properties of swellable polymeric networks. Originally intended for vulcanized rubber, their development has since been extensively used and extended to much more complex systems, such as hydrogels, and used to estimate the mesh size of such networks. In this article, we take a look at the development of the Flory-Rehner equation and highlight several issues that arise when using such a theory for the described hydrogel networks. We then propose a new approach and equations to accurately calculate the backbone molecular weight in-between crosslinks while explicitly accounting for the molecular mass of the crosslinker and branch segments. The approach also provides more applicable mesh dimensions, for complex networks with macromeric crosslinkers and/or a high degree of branching, as is the case of biocompatible hydrogels. The approach is finally illustrated by a case study comparing the values obtained with our proposed approach to those using the state-of-the-art approach.

Co-culture methods to study neuronal function and disease.

Co-culture methods to study neuronal function and disease.

The adaptation of lipid profile of human fibroblasts to alginate 2D films and 3D printed scaffolds

BackgroundThe investigation of the interactions between cells and active materials is pivotal in the emerging 3D printing-biomaterial application fields. Here, lipidomics has been used to explore the early impact of alginate (ALG) hydrogel architecture (2D films or 3D printed scaffolds) and the type of gelling agent (CaCl2 or FeCl3) on the lipid profile of human fibroblasts. Methods2D and 3D ALG scaffolds were prepared and characterized in terms of water content, swelling, mechanical resistance and morphology before human fibroblast seeding (8 days). Using a liquid chromatography-triple quadrupole-tandem mass spectrometry approach, selected ceramides (CER), lysophosphatidylcholines (LPC), lysophosphatidic acids (LPA) and free fatty acids (FFA) were analyzed. ResultsThe results showed a clear alteration in the CER expression profile depending of both the geometry and the gelling agent used to prepare the hydrogels. As for LPCs, the main parameter affecting their distribution is the scaffold architecture with a significant decrease in the relative expression levels of the species with higher chain length (C20 to C22) for 3D scaffolds compared to 2D films. In the case of FFAs and LPAs only slight differences were observed as a function of scaffold geometry or gelling agent. ConclusionsVariations in the cell membrane lipid profile were observed for 3D cell cultures compared to 2D and these data are consistent with activation processes occurring through the mutual interactions between fibroblasts and ALG support. These unknown physiologically relevant changes add insights into the discussion about the relationship between biomaterial and the variations of cell biological functions.

Meshes‐to‐Fibrils Transition of Gellan Gum Hydrogel Architecture by Thermal Annealing

AbstractThe possibilities created by tuning the architecture of hydrogels open up extensive opportunities for their application in tissue engineering and biomedicine. A simple and effective procedure is developed here, based on thermal annealing, which affects the alignment of the fibrils and results in a mesh‐like structure. Atomic force microscopy and cryo‐scanning electron microscopy are used to characterize the resultant gel. The alignment angle is demonstrated to take place spontaneously, providing an easy way for self‐assembly of such structures. The protocol developed here is likely to be applicable in numerous areas of biomedicine and tissue engineering.

Wood hemicelluloses exert distinct biomechanical contributions to cellulose fibrillar networks

Hemicelluloses, a family of heterogeneous polysaccharides with complex molecular structures, constitute a fundamental component of lignocellulosic biomass. However, the contribution of each hemicellulose type to the mechanical properties of secondary plant cell walls remains elusive. Here we homogeneously incorporate different combinations of extracted and purified hemicelluloses (xylans and glucomannans) from softwood and hardwood species into self-assembled networks during cellulose biosynthesis in a bacterial model, without altering the morphology and the crystallinity of the cellulose bundles. These composite hydrogels can be therefore envisioned as models of secondary plant cell walls prior to lignification. The incorporated hemicelluloses exhibit both a rigid phase having close interactions with cellulose, together with a flexible phase contributing to the multiscale architecture of the bacterial cellulose hydrogels. The wood hemicelluloses exhibit distinct biomechanical contributions, with glucomannans increasing the elastic modulus in compression, and xylans contributing to a dramatic increase of the elongation at break under tension. These diverging effects cannot be explained solely from the nature of their direct interactions with cellulose, but can be related to the distinct molecular structure of wood xylans and mannans, the multiphase architecture of the hydrogels and the aggregative effects amongst hemicellulose-coated fibrils. Our study contributes to understanding the specific roles of wood xylans and glucomannans in the biomechanical integrity of secondary cell walls in tension and compression and has significance for the development of lignocellulosic materials with controlled assembly and tailored mechanical properties.

Construction of Organelle-Like Architecture by Dynamic DNA Assembly in Living Cells.

The design of controllable dynamic systems is vital for the construction of organelle-like architectures in living cells, but has proven difficult due to the lack of control over defined topological transformation of self-assembled structures. Herein, we report a DNA based dynamic assembly system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle-like hydrogel architecture in living cells. Designer DNA nanoparticles are constructed from double-stranded DNA with cytosine-rich stick ends (C-monomer) and are internalized into cells through lysosomal pathway. The lysosomal acidic microenvironment can activate the assembly of DNA monomers, inducing transformation from nanoparticles to micro-sized organelle-like hydrogel which could further escape into cytoplasm. We show how the hydrogel regulates cellular behaviors: cytoskeleton is deformed, cell tentacles are significantly shortened, and cell migration is promoted.

Synthesis of resilient hybrid hydrogels using UiO-66 MOFs and alginate (hydroMOFs) and their effect on mechanical and matter transport properties

Herein, we report the preparation of an organic–inorganic hybrid hydrogel architecture using vinyl alginate and UiO-66 MOFs (metal-organic frameworks) modified with acrylic acid (AA) UiO-66AA. UiO-66 MOFs with different crystal sizes (600, 1500, and 2500 nm) were synthesized and the effect on the mechanical and transport properties of the resulting materials, such as water absorption capacity and drug release, were evaluated. HydroMOF showed higher water absorption capacity than the pure hydrogel and enhanced mechanical properties, which depend on crystal size and the amount of UiO-66AA MOF used. The initial release rate of drug (burst release) from hydroMOFs was lower when small-sized crystals or a small amount of large-sized crystals were used; thus these are essential in changing half-life values of release rates. Finally, the cytotoxicity screening successfully showed that hydroMOFs are promising biocompatible compounds proven to have the advantages of minimized burst release and mechanical robustness.

Elucidating the Role of Thermal Flexibility of Hydrogels in Protein Refolding.

Synthetic chaperones are stimuli-responsive materials that facilitate the refolding of denatured proteins in their native form and release refolded proteins in solution in the presence of external stimuli. Thermoresponsive hydrogels are a class of synthetic chaperones that require heat as an external stimulus to refold the denatured proteins into their biologically active conformations; however, the mechanism by which these hydrogels participate in protein refolding mechanism remains unclear. In this study, we explore the role of physical and structural changes in the hydrogel matrix that may participate in protein refolding efficacies of thermally responsive poly(vitamin B5 analogous methacrylamide) poly(B5AMA) hydrogels. Poly(B5AMA) hydrogels of different net charges, hydrophobicity, and cross-linking densities are synthesized by radical polymerization method and are evaluated for the restoration of enzymatic activity of thermally denatured enzymes (lysozyme and carbonic anhydrase) as a function of temperature and time and for the presence of residual water in the hydrogel architecture. The hydrogels with promising protein renaturation efficacies are further evaluated for their interactions with denatured proteins, and the role of thermal flexibility of the hydrogel matrix in protein refolding capabilities is elucidated.

Formulation of Sugar/Hydrogel Inks for Rapid Thermal Response 4D Architectures with Sugar-derived Macropores

Programmed, reshaping hydrogel architectures were fabricated from sugar/hydrogel inks via a three-dimensional printing method involving a stimuli-responsive polymer. We developed a new hydrogel ink composed of monomers (acrylamide [AAm]) and N-isopropylacrylamide [NIPAAm]), and sugar (mixture of glucose and sucrose) as a pore-generator, enabling to improve printability by increasing the ink’s viscoelastic properties and induce the formation of macropores in the hydrogel architectures. This study demonstrated that creating macropores in such architectures enables rapid responses to stimuli that can facilitate four-dimensional printing. We printed bilayer structures from monomer inks to which we had added sugar, and we exposed them to processes that cross-linked the monomers and leached out the sugar to create macropores. In comparison with a conventional poly(N-isopropylacrylamide) hydrogel, the macroporous hydrogels prepared using polymerization in the presence of a high concentration of sugar showed higher swelling ratios and exhibited much faster response rates to temperature changes. We used rheometry and scanning electron microscopy to characterize the properties of these inks and hydrogels. The results suggest that this method may provide a readily available route to the rapid design and fabrication of shape-morphing hydrogel architectures with potential application in soft robotics, hydrogel actuators, and tissue engineering.