Simple Hydrogel Research Articles

Hydrogels with Differentiated Hydrogen‐Bonding Networks for Bioinspired Stress Response

AbstractStress response, an intricate and autonomously coordinated reaction in living organisms, holds a reversible, multi‐path, and multi‐state nature. However, existing stimuli‐responsive materials often exhibit single‐step and monotonous reactions due to the limited integration of structural components. Inspired by the cooperative interplay of extensor and flexor cells within Mimosa's pulvini, we present a hydrogel with differentiated hydrogen‐bonding (H‐bonding) networks designed to enable the biological stress response. Weak H‐bonding domains resemble flexor cells, confined within a hydrophobic network stabilized by strong H‐bonding clusters (acting like extensor cells). Under external force, strong H‐bonding clusters are disrupted, facilitating water diffusion from the bottom layer and enabling transient expansion pressure gradient along the thickness direction. Subsequently, water diffuses upward, gradually equalizing the pressure, while weak H‐bonding domains undergo cooperative elastic deformation. Consequently, the hydrogel autonomously undergoes a sequence of reversible and pluralistic motion responses, similar to Mimosa's touch‐triggered stress response. Intriguingly, it exhibits stress‐dependent color shifts under polarized light, highlighting its potential for applications in time‐sensitive “double‐lock” information encryption systems. This work achieves the coordinated stress response inspired by natural tissues using a simple hydrogel, paving the way for substantial advancements in the development of intelligent soft robots.

Hydrogels with Differentiated Hydrogen-Bonding Networks for Bioinspired Stress Response.

Stress response, an intricate and autonomously coordinated reaction in living organisms, holds a reversible, multi-path, and multi-state nature. However, existing stimuli-responsive materials often exhibit single-step and monotonous reactions due to the limited integration of structural components. Inspired by the cooperative interplay of extensor and flexor cells within Mimosa's pulvini, we present a hydrogel with differentiated hydrogen-bonding (H-bonding) networks designed to enable the biological stress response. Weak H-bonding domains resemble flexor cells, confined within a hydrophobic network stabilized by strong H-bonding clusters (acting like extensor cells). Under external force, strong H-bonding clusters are disrupted, facilitating water diffusion from the bottom layer and enabling transient expansion pressure gradient along the thickness direction. Subsequently, water diffuses upward, gradually equalizing the pressure, while weak H-bonding domains undergo cooperative elastic deformation. Consequently, the hydrogel autonomously undergoes a sequence of reversible and pluralistic motion responses, similar to Mimosa's touch-triggered stress response. Intriguingly, it exhibits stress-dependent color shifts under polarized light, highlighting its potential for applications in time-sensitive "double-lock" information encryption systems. This work achieves the coordinated stress response inspired by natural tissues using a simple hydrogel, paving the way for substantial advancements in the development of intelligent soft robots.

A Mn2+‐Assisted Nanofiber‐Hydrogel Adjuvant for Simultaneous Enhancement of Humoral and Cellular Immune Responses

AbstractLimited ability to elicit cellular immune responses has restricted the effectiveness of conventional adjuvants in the context of cancers. Recent advancements in innate immune activation mechanism investigations have paved the way for the implementation of a “bottom‐up” approach in the development of novel adjuvants. Herein, a simple hydrogel adjuvant with a uniformly organized nanoscale microstructure, termed MnPgel is devised, by employing self‐assembling peptides incorporated with manganese ions (Mn2+). MnPgel exhibits Mn2+ sustained‐release properties in vivo and effectively promotes germinal center formation, thereby facilitating the generation of antibodies at levels comparable to conventional aluminum‐based adjuvants. Moreover, MnPgel transcends the scope of humoral immunity, demonstrating the ability to robustly trigger cellular immune responses and positioning it as a promising candidate for cancer prevention and treatments. In conclusion, the work has introduced a well‐defined hydrogel adjuvant as a proof‐of‐concept, simplifying vaccine adjuvant design and opening up new avenues for “on‐demand” immunomodulation strategies.

Design, characterization, and performance evaluation of novel PVA/CS/CNF/MOP TN ionic conductive hydrogels for flexible sensors

AbstractFlexible hydrogel polymers with excellent stretchability, high conductivity, and biocompatibility are widely used to prepare flexible sensing devices. However, it remains difficult to simultaneously combine excellent tensile capacity and high ion conducting ability into a simple hydrogel material. While PVA‐based hydrogels have been developed before, this work focuses on a unique preparation method. It solves the engineering problem of making hydrogels that have both high elongation at break and high ionic conductivity. In the study, we introduced cellulose nanofibers (CNFs) into polyvinyl alcohol (PVA)/chitosan (CS) cross‐linked polymer networks to form triple network (TN) composite hydrogel. The labyrinthine three‐dimensional (3D) honeycomb through‐hole network nanostructure generated by the addition of CNF provides the hydrogel with excellent mechanical properties. Then, the simple salting‐out strategy of muriate of potash (MOP) solution gives the hydrogel superior mechanical properties and high ionic conductivity. The prepared PVA/CS/CNF/MOP TN ionic conductive hydrogel not only exhibits excellent mechanical properties (toughness up to 2.39 MJ m−3, fracture strength up to 1.78 MPa, fracture strain up to 350%) but also has impressive ionic conductivity (highest to 8.4 S m−1). The flexible hydrogel strain sensor assembled from the PVA/CS/CNF/MOP TN ionic conductive hydrogel showed remarkable sensitivity (gauge factor for 6.9) and the ability to detect human motions reliably. Besides, the hydrogel also has maintained long‐term antimicrobial and antioxidant properties. The study provided a new perspective on designing multifunctional materials featuring strong mechanical properties and high ionic conductivity, contributing to the advancement of flexible sensor technologies.

Properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle Chlorella and its effects on healing of infected full-thickness skin defect wounds in mice

Properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle Chlorella and its effects on healing of infected full-thickness skin defect wounds in mice

GelMA-catechol coated FeHAp nanorods functionalized nanofibrous reinforced bio-instructive and mechanically robust composite hydrogel scaffold for bone tissue engineering

Critical bone defects complicate tissue graft-based surgeries, raising healthcare expenditures and underscoring scaffold-based tissue-engineering strategies to support bone reconstruction. Our study highlighted that the phase-compatible combination of inorganic nanorods, nanofibers, and hydrogels is promising for developing biomimetic and cell-instructive scaffolds since the bone matrix is a porous organic/inorganic composite. In brief, methacrylated gelatin (GelMA) was reacted with dopamine to form catechol-modified GeLMA (GelMA-C). The GelMA-C was nanocoated onto an iron-doped hydroxyapatite (FeHAp) nanorod via metal-catechol network coordination. The modified nanorod (FeHAp@GelMA-C) was loaded onto GelMA-based nanofibers. The nanorods loaded pre-fibers were electrospun onto GelMA solution and photochemically crosslinked to fabricate a fiber-reinforced hydrogel. The structural, mechanical, physicochemical, biocompatibility, swelling properties, osteogenic potential, and bone remodelling potential (using rat femoral defect model) of modified nanorods, simple hydrogel, and nanorod-loaded fiber-reinforced hydrogel were studied. The results supported that the interface interaction between GelMA-C/nanorods, nanorods/nanofibers, nanorods/hydrogels, and nanofiber/hydrogels significantly improved the microstructural and mechanical properties of the scaffold. Compared to pristine hydrogel, the nanorod-loaded fiber-reinforced scaffold better supported cellular responses, osteogenic differentiation, matrix mineralization, and accelerated bone regeneration. The nanorod-loaded fiber-reinforced hydrogel proved more biomimetic and cell-instructive for guided bone reconstruction.

Adsorption-photocatalytic degradation abilities of γ-irradiated chitosan-ZnO-AgNP composite for organic dye removal and antibacterial activity.

We synthesized a γ-irradiated chitosan-ZnO-AgNPs (ICZA) composite by using a simple hydrogels method. We evaluated its adsorption/photocatalytic degradation abilities for the removal of an organic dye and its antibacterial activity. The XRD, SEM, TEM, EDS, and FTIR techniques were used to characterize the obtained samples. Based on the adsorption and degradation of methylene blue (MB) in the dark and under UV light irradiation, the adsorption and the photocatalytic activity of the as-obtained samples were evaluated. The optimum conditions for synthesizing the composite were as follows: contact time of 210 min, a dosage of 2 g/L, MB concentration of 40 mg/L, and a solution pH of 8.0. The ICZA had a high adsorption capacity, which was suitable for removing MB from the aqueous solutions; it showed a maximum adsorption capacity (qm) of 92.59 mg/g. The fit of the adsorption isotherms with the Langmuir model was satisfactory. The photocatalytic degradation ability of the composite was also better than that of other catalysts in the presence of UV light, with an apparent rate constant (kapp) of 3.08 × 10-2. The synthesized ICZA also showed good antibacterial activity against Staphylococcus aureus, with a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 12.5g/mL and 50g/mL under light-incubation and dark-incubation conditions. Finally, we discussed the hypothesized mechanism of the adsorption/photocatalytic activity and antibacterial activity of the ICZA composite in this study.

One-Pot Synthesis of Double-Network PEG/Collagen Hydrogel for Enhanced Adipogenic Differentiation and Retrieval of Adipose-Derived Stem Cells.

Hydrogels are widely used in stem cell therapy due to their extensive tunability and resemblance to the extracellular matrix (ECM), which has a three-dimensional (3D) structure. These features enable various applications that enhance stem cell maintenance and function. However, fast and simple hydrogel fabrication methods are desirable for stem cells for efficient encapsulation and to reduce adverse effects on the cells. In this study, we present a one-pot double-crosslinked hydrogel consisting of polyethylene glycol (PEG) and collagen, which can be prepared without the multi-step sequential synthesis of each network, by using bio-orthogonal chemistry. To enhance the adipogenic differentiation efficiency of adipose-derived stem cells (ADSCs), we added degradable components within the hydrogel to regulate matrix stiffness through cell-mediated degradation. Bio-orthogonal reactions used for hydrogel gelation allow rapid gel formation for efficient cell encapsulation without toxic by-products. Furthermore, the hybrid network of synthetic (PEG) and natural (collagen) components demonstrated adequate mechanical strength and higher cell adhesiveness. Therefore, ADSCs grown within this hybrid hydrogel proliferated and functioned better than those grown in the single-crosslinked hydrogel. The degradable elements further improved adipogenesis in ADSCs with dynamic changes in modulus during culture and enabled the retrieval of differentiated cells for potential future applications.

Super-anti-freezing, tough and adhesive titanium carbide and L-ornithine-enhanced hydrogels

Hydrogels are highly porous three-dimensional crosslinked polymer networks consisting of hydrophilic polymers, employed most practically in medicine and industry, often as biosensors. Simple hydrogels suffer limitations in their mechanical properties, such as tensile and compression, and freeze at sub-zero temperatures, which compromise their ability as useful biosensors. In this study, the incorporation of L-ornithine-based zwitterionic monomer (OZM), titanium carbide (MXene), and glycerol within polyacrylamide hydrogels was used to prepare a novel polyacrylamide/polyL-ornithine-based zwitterion/MXene (PAM/Porn/MXene) hydrogel to improve the mechanical, adhesion, and anti-freezing properties of pure polyacrylamide hydrogels. This study also analyzed the mechanical strength (tensile and compression), adhesion, and anti-freezing properties of a novel PAM/Porn/MXene hydrogel at 1%, 4%, and 10% MXene concentrations to establish to what extent the conductive MXene material enhanced these properties and concluded that the tensile and compressive properties improved linearly with the increase in the concentrations of MXene, adhesion decreased with the increased MXene concentrations, and synergistic interaction between MXene and OZM significantly improved the anti-freezing properties up to –80 °C.

Ultrafast and absolute quantification of SARS-CoV-2 on food using hydrogel RT-LAMP without pre-lysis.

With rapid growing of environmental contact infection, more and more attentions are focused on the precise and absolute quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus on cold chain foods via point-of-care test (POCT). In this work, we propose a hydrogel-mediated reverse transcription loop-mediated isothermal amplification (RT-LAMP) for ultrafast and absolute quantification of SARS-CoV-2. Cross-linked hydrogel offers opportunities for digital single molecule amplification in nanoconfined spaces, facilitating the virus lysis, RNA reverse transcription and amplification process, which is about 3.4-fold faster than conventional bulk RT-LAMP. Ultrafast quantification of SARS-CoV-2 is accomplished in 15 min without virus pre-lysis and RNA extraction. The sensitivity can accurately quantify SARS-CoV-2 down to 0.5 copy/μL. Furthermore, the integrated system has an excellent specificity, reproducibility and storage stability, which can be also used to test SARS-CoV-2 on various cold chain fruits. The developed ultrafast and simple hydrogel RT-LAMP will be an enormous potential for surveillance of virus or other hazardous microbes in environmental, agricultural and food industry.

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery.

(1) Background: Chitosan-gelatin-based thermosensitive hydrogel containing 5FU-alginate nanoparticles was formulated for the effective and sustained delivery of 5FU to the skin. (2) Methods: Alginate, a polysaccharide was used for the formulation of nanoparticles using a spray drying technique. Size, zeta potential, and surface morphology were investigated using a zetasizer and scanning electron microscope. The hydrogel was fabricated using chitosan and gelatin. Several important analyses were used to characterize these prepared topical hydrogels. The pH, visual transparency, rheological behavior, and swelling index of the prepared hydrogels were evaluated. The in vitro release studies were performed at different pH (5.5 and 7.4) and temperature (32 and 37 °C) conditions using a Franz diffusion cell. Ex vivo permeation and in vivo studies were performed using Sprague Dawley rats. (3) Results: Results show that spherical nanoparticles were produced at sizes of 202–254 nm and with zeta potentials of −43 to −38 mV. The prepared nanoparticles were successfully incorporated into chitosan-gelatin-based hydrogels using a glycerol 2-phosphate disodium salt hydrates crosslinker. Drug polymers and excipients compatibility and formulation of hydrogels was confirmed by ATR-FTIR results. The pH of the prepared hydrogels was in accordance with the skin pH. The viscosity of prepared hydrogel increased with temperature increase and phase transition (sol-gel transition) occurred at 34 °C. The release of drug was sustained in case of nanoparticles incorporated hydrogels (5FU-Alg-Np-HG) as compared to nanoparticles (5FU-Alg-Np) and simple hydrogels (5FU-HG) (ANOVA; p < 0.05). The premature and initial burst release of 5FU was prevented using 5FU-Alg-Np-HG. The release mechanism of 5FU from the 5FU-Alg-Np-HG diffusion was followed by swelling and erosion, as suggested by Korsmeyer-Peppas model. The prepared hydrogel proved to be non-irritant. Ex vivo permeation study across rat’s skin suggests that permeability of nanoparticles (5FU-Alg-Np) was higher than the 5FU-Alg-Np-HG (ANOVA; p < 0.05). However, skin-related drug retention of 5FU-Alg-Np-HG was significantly higher than the 5FU solution, 5FU-Alg-Np, and 5FU-HG (ANOVA; p < 0.05). This was due to swelling of hydrogels in the lower layers of skin where the temperature is 37 °C. The higher concentration of 5FU in the skin is helpful for treatment of local skin cancer, such as melanoma, and actinic keratosis. In vivo results also confirmed maximum AUC, t1/2, and skin-related drug retention of 5FU-Alg-Np-HG. (4) Conclusions: Chitosan-gelatin-based hydrogels containing 5FU-Alg-Np possess exceptional properties, and can be used for the sustained delivery of 5FU for the treatment of local skin cancers.

Marrying the incompatible for better: Incorporation of hydrophobic payloads in superhydrophilic hydrogels

HypothesisThe entrapment of lyophobic in superhydrophilic hydrogels is challenging because of the intrinsic incompatibility between hydrophobic and hydrophilic molecules. To achieve such entrapment without affecting the hydrogel’s formation, the electrospinning of nanodroplets or nanoparticles with a water-soluble polymer could reduce the incompatibility through the reduction of interfacial tension and the formation of a barrier film preventing coalescence or aggregation. ExperimentsNanodroplets or nanoparticles dispersion are electrospun in the presence of a hydrophilic polymer in hydrogel precursors. The dissolution of the hydrophilic nanofibers during electrospinning allows a redispersion of emulsion droplets and nanoparticles in the hydrogel’s matrix. FindingsSuperhydrophilic hydrogels with well-distributed hydrophobic nanodroplets or nanoparticles are obtained without detrimentally imparting the viscosity of hydrogel’s precursors and the mechanical properties of the hydrogels. Compared with the incorporation of droplets without electrospinning, higher loadings of hydrophobic payload are achieved without premature leakage. This concept can be used to entrap hydrophobic agrochemicals, drugs, or antibacterial agents in simple hydrogels formulation.

Drug diffusion in biomimetic hydrogels: importance for drug transport and delivery in non-vascular tumor tissue

Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood.

Gradient Hydrogels-Overview of Techniques Demonstrating the Existence of a Gradient.

Gradient hydrogels are promising future materials which could be usable in tissue engineering (scaffolds), pharmaceutical (drug delivery systems with controlled release) and many others related disciplines. These hydrogels exhibit a more complex inner (gradient) structure (e.g., concentration gradient) than simple isotropic hydrogel. Gradient-structured hydrogels could be beneficial in, for example, understanding intercellular interactions. The fabrication of gradient hydrogels has been relatively deeply explored, but a comprehensive description of the physico-chemical techniques demonstrating the existence of a gradient structure is still missing. Here, we summarize the state-of-the-art available experimental techniques applicable in proving and/or describing in physico-chemical terms the inner gradient structure of hydrogels. The aim of this paper is to give the reader an overview of the existing database of suitable techniques for characterizing gradient hydrogels.

Rational design of a supramolecular hydrogel with customizable pH-responsiveness on the basis of pH-induced ionization/protonation transition of BSA.

Developing customizable pH-responsiveness for supramolecular hydrogels is of great significance and has drawn tremendous attention. Through systematic simulation analysis, we formulated a simple supramolecular hydrogel (i.e., poly(AAm-co-NaSS)/BSA on the basis of electrostatic interaction between the sulfonate groups of poly(AAm-co-NaSS) and the protonated side groups of BSA, and proposed a novel pH-responsive mode for it: changing the internal electric charge composition of the hydrogel through pH-induced ionization/protonation transition of BSA, thereby regulating the structural stability/shrinkage/extension of the supramolecular network. On basis of this theory, the pH-responsiveness of the poly(AAm-co-NaSS)/BSA hydrogel, in principle, could be pre-designed by adjusting the initial BSA/NaSS ratio. In this regard, we fabricated a poly(AAm-co-NaSS)/BSA hydrogel prototype with a BSA/NaSS ratio of 1/57 and investigated its rheological/swelling/disassembling behavior under different pH conditions (1.7, 4.7, 7.7, 10.7, and 13.7). In addition, we also prepared two capecitabine-loaded poly(AAm-co-NaSS)/BSA hydrogel prototypes with BSA/NaSS ratios of 1/57 and 1/102 respectively at pH 4.0, and compared their drug release behavior in SGF and SIF. Finally, the experimental results fitted well with our theoretical expectations, which testified the rationality of our assumption. Thus, we believed that the poly(AAm-co-NaSS)/BSA supramolecular hydrogel could find diverse applications in the future.

Hydrogel Coatings on Container Surfaces Reduce Protein Aggregation Caused by Mechanical Stress and Cavitation.

This work reports the ability of hydrogel coatings to protect therapeutic proteins from cavitation-induced aggregation caused by mechanical stress. Here, we show that polyacrylamide hydrogel coatings on container surfaces suppress mechanical shock-induced cavitation and the associated aggregation of intravenous immunoglobulin (IVIg). First, crosslinked polyacrylamide hydrogels were grown on the surfaces of borosilicate glass vials. Treatment with ultrasound showed that these hydrogel surfaces suppressed cavitation events to levels below those found for unfunctionalized borosilicate glass. Next, IVIg solutions were loaded into these vials and subjected to tumbling, horizontal shaking, and drop testing. Aggregation was quantified by bisANS fluorescence staining and particle counting by flow imaging microscopy (FIM). In all cases, the presence of polyacrylamide hydrogels on the vial surfaces reduced the amount of IVIg aggregation and the number of particulates. In addition, the polyacrylamide appeared to have a protective effect that prevented additional aggregates from forming at extended tumbling times. Finally, drop test studies showed that the polyacrylamide coatings suppressed detectable cavitation. This work reveals how even a simple hydrogel vial coating can have a profound effect on stabilizing protein therapeutics.

Supramolecular hydrogelation via host-guest anion recognition: Lamellar hydrogel materials for the release of cationic cargo

Supramolecular hydrogelation via host-guest anion recognition: Lamellar hydrogel materials for the release of cationic cargo

Agarose composite hydrogel and PVA sacrificial materials for bioprinting large-scale, personalized face-like with nutrient networks

Large, deep, complex, and severe tissue defects and deformities of the face are the problems encountered in clinical practice. Autologous tissue reconstruction or allograft face transplantation has been adopted but has problems such as blood supply difficulties, collateral damage, immune rejection, and ethical disputes. 3D bioprinting enables personalized tissue regeneration. However, simple hydrogels are prone to collapse during printing, are limited in size, and have poor shape and structure. The present study used three polysaccharide hydrogel composites of nanocellulose, agarose, and sodium alginate with seeded cells as bioinks and polyvinyl alcohol (PVA) as sacrificial material to construct the structures that did not collapse (characteristic parts, such as lips and nose). The nutrient network gradually formed a blood vessel-like structure. The hydrogels prepared using these three polysaccharides have great potential in the construction of personalized, complex, and vascularized tissue-engineered anatomical faces and provide a new strategy for autologous full face reconstruction.

Composite hydrogel makes durable heart valves

With a new durable composite hydrogel, researchers have 3D printed heart valves that last nearly 100 times as long as valves made with a simple hydrogel ( Matter 2021, DOI: 10.1016/j.matt.2021.03.0...

Advances in biofabrication techniques for collagen-based 3D in vitro culture models for breast cancer research

Collagen is the most abundant component of the extracellular matrix (ECM), therefore it represents an ideal biomaterial for the culture of a variety of cell types. Recently, collagen-based scaffolds have shown promise as 3D culture platforms for breast cancer-based research. Two-dimensional (2D) in vitro culture models, while useful for gaining preliminary insights, are ultimately flawed as they do not adequately replicate the tumour microenvironment. As a result, they do not facilitate proper 3D cell-cell/cell-matrix interactions and often an exaggerated response to therapeutic agents occurs. The ECM plays a crucial role in the development and spread of cancer. Alterations within the ECM have a significant impact on the pathogenesis of cancer, the initiation of metastasis and ultimate progression of the disease. 3D in vitro culture models that aim to replicate the tumour microenvironment have the potential to offer a new frontier for cancer research with cell growth, morphology and genetic properties that more closely match in vivo cancers. While initial 3D in vitro culture models used in breast cancer research consisted of simple hydrogel platforms, recent advances in biofabrication techniques, including freeze-drying, electrospinning and 3D bioprinting, have enabled the fabrication of biomimetic collagen-based platforms that more closely replicate the breast cancer ECM. This review highlights the current application of collagen-based scaffolds as 3D in vitro culture models for breast cancer research, specifically for adherence-based scaffolds (i.e. matrix-assisted). Finally, the future perspectives of 3D in vitro breast cancer models and their potential to lead to an improved understanding of breast cancer diagnosis and treatment are discussed.