Alginate Hydrogel Research Articles

Fabrication and investigation of a pentamerous composite based on calix[4]arene functionalized graphene oxide grafted with silk fibroin, cobalt ferrite, and alginate

This paper presents a new scaffold made from graphene oxide nanosheets, calix[4]arene supramolecules, silk fibroin proteins, cobalt ferrite nanoparticles, and alginate hydrogel (GO-CX[4]/SF/CoFe2O4/Alg). After preparing the composite, we conducted various analyses to examine its structure. These analyses included FTIR, XRD, SEM, EDS, VSM, DLS, and zeta potential tests. Additionally, we performed tests to evaluate the swelling ratio, rheological properties, and compressive mechanical strength of the material. The biological capability of the composite was tested through biocompatiblity, anticancer, hemolysis, antibacterial anti-biofilm assays. Besides, the rheological properties and swelling behaviour of the composite were studied. The results showed that the scaffold is biocompatible with Hu02 cells and the cell viability percentages of 85.23 %, 82.78 %, and 80.18 % for were acquired for 24, 48, and 72 h, respectively. In contrast, the cell viability percentage of BT549 cancer cells were obtained 65.79 %, 60.45 % and 58.16 % for same period which confirmed notable anticancer activity of the product composite. Moreover, a significant antibacterial growth inhibition against E. coli and S. aureus species highlights its potential as an effective antibacterial agent. Furthermore, the observed minimal hemolytic effect (6.56 %) and strong inhibition of P. aeruginosa biofilm formation with a low OD value (0.24) indicate notable hemocompatibility and antibacterial activity.

3D Hydrogel Encapsulation Regulates Nephrogenesis in Kidney Organoids.

Stem cell-derived kidney organoids contain nephron segments that recapitulate morphological and functional aspects of the human kidney. However, directed differentiation protocols for kidney organoids are largely conducted using biochemical signals to control differentiation. Here, the hypothesis that mechanical signals regulate nephrogenesis is investigated in 3D culture by encapsulating kidney organoids within viscoelastic alginate hydrogels with varying rates of stress relaxation. Tubular nephron segments are significantly more convoluted in kidney organoids differentiated in encapsulating hydrogels when compared with those in suspension culture. Hydrogel viscoelasticity regulates the spatial distribution of nephron segments within the differentiating kidney organoids. Consistent with these observations, a particle-based computational model predicts that the extent of deformation of the hydrogel-organoid interface regulates the morphology of nephron segments. Elevated extracellular calcium levels in the culture medium, which can be impacted by the hydrogels, decrease the glomerulus-to-tubule ratio of nephron segments. These findings reveal that hydrogel encapsulation regulates nephron patterning and morphology and suggest that the mechanical microenvironment is an important design variable for kidney regenerative medicine.

Application of modified sodium alginate hydrogel for interventional embolization of hemorrhagic diseases

Traditional particulate embolic agents are small in diameter, but can easily embolize the ends of blood vessels, resulting in ischemia and necrosis of normal tissues and organs. The metal spring embolic agent has a larger diameter, but it cannot be degraded and can easily cause permanent damage to blood vessels. Ideally, a bleeding embolism should achieve rapid hemostasis without causing long-term necrosis of organs and tissues. In this study, a modified sodium alginate hydrogel (MSAH) was prepared by mixing an oxidized sodium alginate (OSA) aqueous solution with a carboxymethyl chitosan (CMC) aqueous solution at a ratio of 1:6 in a 38°C bath for 8 min. The feasibility of this modified hydrogel was then tested in an internal iliac artery hemorrhage model using New Zealand rabbits. The MSAH had good adhesion. The hydrogel was injected through a single curved 4F catheter without obvious effects on uterine smooth muscle cell proliferation and apoptosis. The blood flow of the internal iliac artery was restored by long-term degradation of the sodium alginate hydrogel, and no ischemia and necrosis were observed by histopathology. The MSAH prepared using a mixture of OSA and CMC had good adhesion, biocompatibility, and injectability and could be used for target-vessel embolization in an internal iliac artery hemorrhage model. The MSAH can achieve main artery embolization without affecting the peripheral artery blood supply, resulting in both short-term rapid hemostasis and long-term degradation, with no target organ necrosis.

Development of alginate macroporous hydrogels using sacrificial CaCO3 particles for enhanced hemostasis

Polymeric hydrogels have increasingly garnered attention in the field of hemostasis. However, there remains a lack of targeted development and evaluation of non-dense polymeric hydrogels with physically incorporated pores to enhance hemostasis. Here, we present a facile route to macroporous alginate hydrogels using acid-induced CaCO3 dissolution to provide Ca2+ for alginate gelation and CO2 bubbles for subsequent macropore formation. The as-prepared pore structure in the hydrogels and its formation mechanisms were characterized through microscopic imaging and nitrogen adsorption/desorption tests. Functional analyses revealed that the macroporous hydrogels exhibited improved rheology, blood absorption, coagulation factor delivery, and platelet aggregation. Ultimately, the introduction of pores significantly enhanced the hemostatic effectiveness of alginate hydrogels in vivo, as demonstrated in rat tail amputation and liver injury models, leading to a reduction in blood loss of up to 77 % or a decrease in bleeding time of up to 88 %. Notably, hydrogels with higher porosity achieved with a CaCO3 to alginate ratio of 40 % outperformed those with lower porosity in the aforementioned properties. Furthermore, these improvements were found to be biocompatible and elicited minimal inflammation. Our findings underscore the potential of a simple porous hydrogel design to enhance hemostasis efficacy by physically incorporating macropores.

Fabrication of maleic anhydride-acrylamide copolymer based sodium alginate hydrogel for elimination of metals ions and dyes contaminants from polluted water

The study explores the synergy of biobased polymers and hydrogels for water purification. Polymer nanomaterial's, synthesized by combining acrylamide copolymer with maleic anhydride, were integrated into sodium alginate biopolymer using an eco-friendly approach. Crosslinking agents, calcium chloride and glutaraladehyde, facilitated seamless integration, ensuring non-toxicity, high adsorption performance, and controlled capacity. This innovative combination presents a promising solution for clean and healthy water supplies, addressing the critical need for sustainable environmental practices in water purification. In addition, the polymer sodium alginate hydrogel (MAH@AA-P/SA/H) underwent characterization via the use of several analytical procedures, such as FTIR, XPS, SEM, EDX and XRD. Adsorption studies were conducted on metals and dyes in water, and pollutant removal methods were explored. We investigated several variables (such as pH, starting concentration, duration, and absorbent quantity) affect a material's capacity to be adsorbed. Moreover, the maximum adsorption towards Cu2+ is 754 mg/g while for Cr6+ metal ions are 738 mg/g, while the adsorption towards Congo Red and Methylene Blue dye are 685 mg/g and 653 mg/g correspondingly, within 240 min. Adsorption results were further analyzed using kinetic and isothermal models, which showed that MAH@AA-P/SA/H adsorption is governed by a chemisorption process. Hence, the polymer prepared from sodium alginate hydrogel (MAH@AA-P/SA/H) has remarkable properties as a versatile material for the significantly elimination of harmful contaminants from dirty water.

The Effect of pH on the Viscoelastic Response of Alginate-Montmorillonite Nanocomposite Hydrogels.

Ionically cross-linked alginate hydrogels are used in a wide range of applications, such as drug delivery, tissue engineering, and food packaging. A shortcoming of these gels is that they lose their strength and degrade at low pH values. To develop gels able to preserve their integrity in a wide range of pH values, Ca-alginate-montmorillonite nanocomposite gels are prepared, and their chemical structure, morphology, and mechanical response are analyzed. As the uniformity of nanocomposite gels is strongly affected by concentrations of MMT and CaCl2, it is revealed that homogeneous gels can be prepared with 4 wt.% MMT and 0.5 M CaCl2 at the highest. The viscoelastic behavior of nanocomposite gels in aqueous solutions with pH = 7 and pH = 2 is investigated by means of small-amplitude compressive oscillatory tests. It is shown that Ca-alginate-MMT nanocomposite gels preserve their integrity while being swollen at pH = 2. The experimental data are fitted by a model with only two material parameters, which shows that the elastic moduli increase linearly with a concentration of MMT at all pH values under investigation due to formation of physical bonds between alginate chains and MMT platelets. The presence of these bonds is confirmed by ATR-FTIR spectroscopy. The morphology of nanocomposite gels is studied by means of wide-angle X-ray diffraction, which reveals that intercalation of polymer chains between clay platelets increases the interlayer gallery spacing.

A simple and efficient alginate hydrogel combined with surface-enhanced Raman spectroscopy for quantitative analysis of sodium nitrite in meat products.

Sodium nitrite is a commonly used preservative and color protectant in the food industry. Conventional analytical methods are highly susceptible to food matrix interference, time-consuming and costly. In this study, the ion cross-linking method was employed to prepare alginate hydrogel substrates, and phenosafranin was chosen as a single-molecule probe to analyze sodium nitrite. Our investigation centered on elucidating the effects of alginate and cross-linking ion concentrations on Raman signal characteristics. The optimal Raman response was observed in the precursor solution with 1% sodium alginate and 0.1 mol L-1 cross-linking ions. The relative standard deviations (RSDs) of the feature peaks from the three substrate batches ranged from 1.22% to 16.30%, attesting the robustness and consistency of the substrates. The signal reduction of the substrates after a four-week storage period remained below 10%, indicating that the substrates had good reproducibility and stability. The limits of detection (LODs) for sodium nitrite in extracts from cured meat, luncheon meat, and sliced ham were determined to range from 3.75 mg kg-1 to 8.11 mg kg-1, with low interference from the food matrix. The support vector machine algorithm was utilized to train and predict the data, which proved to be more accurate (98.6%-99.8% recovery) than the traditional linear regression model (81.9%-112.7% recovery) in predicting the spiked samples. The application of hydrogel-based surface-enhanced Raman spectroscopy (SERS) substrates for nitrite detection in food, combined with machine learning for regression prediction in data processing, collectively augmented the potential of SERS technology in the field of food analysis.

Development of a powdered activated charcoal sodium alginate hydrogel bead concentration method for detecting viruses in wastewater

Developing a simple and cost-effective wastewater concentration method using powdered activated charcoal sodium alginate (PAC-NaA) hydrogel beads, enhanced for capturing viruses.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

Reusable isotype heterojunction g-C3N4/alginate hydrogel spheres for photocatalytic wastewater treatment.

Various visible-light-driven photocatalysts have been studied for practical applications in photocatalytic wastewater treatment via solar irradiation. Among them, g-C3N4 has attractive features, including its metal-free and environmentally friendly nature; however, it is prone to charge recombination and has low photocatalytic activity. To solve these problems, isotype heterojunction g-C3N4 was recently developed; however, the methods employed for synthesis suffered from limited reproducibility and efficiency. In this study, isotype heterojunction g-C3N4 was synthesized from various combinations of precursor materials using a planetary ball mill. The isotype heterojunction g-C3N4 synthesized from urea and thiourea showed the highest photocatalytic activity and completely decolorized Rhodamine B (RhB; 10 ppm) in 15 min under visible-light irradiation. Furthermore, to improve recyclability, isotype heterojunction g-C3N4 was immobilized in alginate hydrogel spheres. The isotype heterojunction g-C3N4/alginate hydrogel beads were used in 10 repeated RhB degradation experiments and were able to maintain their initial photocatalytic activity and mechanical strength. These achievements represent an advance towards practical, sustainable photocatalytic wastewater treatment.

Protein Isolation from 3D Hydrogel Scaffolds.

Protein isolation is an essential tool in cell biology to characterize protein abundance under various experimental conditions. Several protocols exist, tailored to cell culture or tissue sections, and have been adapted to particular downstream analyses (e.g., western blotting or mass spectrometry). An increasing trend in bioengineering and cell biology is to use three-dimensional (3D) hydrogel-based scaffolds for cell culture. In principle, the same protocols can be used to extract protein from hydrogel-based cell and tissue constructs. However, in practice the yield and quality of the recovered protein pellet is often substantially lower when using standard protocols and requires tuning of multiple steps, including the selected lysis buffer and the scaffold homogenization strategy, as well as the methods for protein purification and reconstitution. We present here specific protocols tailored to common 3D hydrogels to help researchers using hydrogel-based 3D cell culture improve the quantity and quality of their extracted protein. We focus on three materials: protease-degradable PEG-based hydrogels, collagen hydrogels, and alginate hydrogels. We discuss how the protein extraction procedure can be adapted to the scaffold of interest (degradable or non-degradable gels), proteins of interests (soluble, matrix-bound, or phosphoproteins), and downstream biochemical assays (western blotting or mass spectrometry). With the growing interest in 3D cell culture, the protocols presented should be useful to many researchers in cell biology, protein science, biomaterials, and bioengineering communities. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolating proteins from PEG-based hydrogels Basic Protocol 2: Isolating proteins from collagen hydrogels Basic Protocol 3: Isolating proteins from alginate hydrogels Alternate Protocol: Isolating protein from alginate gels using EDTA to dissolve the gel Support Protocol: Isolating protein and RNA simultaneously from the same samples.

Peroxynitrite Modification as a Way to Improve the Cytocompatibility of Sodium Alginate-Based Hydrogels

Sodium alginate is one of the most frequently used materials in biomedicine. However, alginate-based scaffolds have extremely low adhesive properties and have to be improved. The authors have proposed combined hydrogels of gelatin and sodium alginate which have been modified by peroxynitrite in heterophasic conditions using ethanol. It has been determined that thus modified sodium alginate contains an increased level of carbonyl, carboxyl and nitro groups. Authors have developed chemically and chemical-enzymatically cross-linked hydrogels with better adhesive properties and absence of cytotoxicity. Moreover, sodium alginate modification has a positive impact on cell morphology in comparison with control group of non-adhesive alginate-gelatin hydrogels. It allows the further improvement and application of the biomaterial which have been developed by the authors for bioengineering scaffold production and 3D culturing.

Reconfiguring the endogenous electric field of a wound through a conductive hydrogel for effective exudate management to enhance skin wound healing.

The ionic environment has a strong influence on the bioelectricity of skin, which is also present in the wound healing process. Inspired by this, we proposed a mechanism for hydrogel-based dressings to respond to endogenous electric fields through exudate absorption and conducted a verification study using a typical hydrogel, namely, polyacrylamide and sodium alginate (PAM-SA) hydrogels, as an example. Theoretical calculations showed that the PAM-SA hydrogels could absorb and orient the various electrolytes of exudate in the hydrogel at the wound site, contributing to the reconstruction of the electric field at the wound site. During the treatment process, this effect significantly accelerated the healing process of the rat epidermis, which exceeded the conventional dressing in terms of healing speed and efficacy, and the wounds on the complete layer of rat skin (wound area: 1.13 cm2) could be rapidly repaired within 10 days. Revealing the electrophysiological behavior of PAM-SA dressings during wound healing can help further improve the design model, the optimization concept, and development paths for the bioelectrical structures of modern dressings and bioelectrical stimulation in wound healing.

Exosomes derived from mucoperiosteum Krt14+Ctsk+ cells promote bone regeneration by coupling enhanced osteogenesis and angiogenesis.

Repair of large bone defects is a sophisticated physiological process involving the meticulous orchestration of cell activation, proliferation, and differentiation. Cellular interactions between different cell types are paramount for successful bone regeneration, making it a challenging yet fascinating area of research and clinical practice. With increasing evidence underscoring the essential role of exosomes in facilitating intercellular and cell-microenvironment communication, they have emerged as an encouraging therapeutic strategy to promote bone repair due to their non-immunogenicity, diverse sources, and potent bioactivity. In this study, we characterized a distinctive population of Krt14+Ctsk+ cells from the orbital mucoperiosteum. In vitro experiments confirmed that exosomes from Krt14+Ctsk+ cells dramatically boosted the capacities of human umbilical vein endothelial cells (HUVECs) to proliferate, migrate, and induce angiogenesis. Additionally, the exosomes notably elevated the expression of osteogenic markers, thereby indicating their potential to augment osteogenic capabilities. Furthermore, in vivo experiments utilizing a rat calvarial defect model verified that exosome-loaded sodium alginate (SA) hydrogels accelerated local vascularized bone regeneration within the defective regions. Collectively, these findings suggest that exosomes secreted by Krt14+Ctsk+ cells offer an innovative method to accelerate bone repair via coupling enhanced osteogenesis and angiogenesis, highlighting the therapeutic potential in bone repair.

A separation-free paper-based hydrogel device for one-step reactive oxygen species determination by a smartphone.

Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity separation. This study reports a novel hydrogel-coupled, paper-based analytical device (PAD) for separation-free H2O2 colorimetric detection in both aqueous solution and cell lysis with sample-to-answer analysis by directly loading into the sample test zone. By encapsulating an inorganic mimic enzyme and chromogenic substrate into the sodium alginate (SA) hydrogel, amplification of the color signal after catalyzing the substrate could be achieved. Taking advantage of the nanoscale porous structure of the hydrogel and the lateral flow channel of the PAD, large interference fragments or bio-macromolecules are prevented from diffusing into the chromogenic reaction, whereas the small target molecules enter the sensing region to trigger the catalytic reaction. This method demonstrated a rapid and accurate analysis with a limit of detection as low as 0.06 mM and detection selectivity. Our proposed device requires no enzyme and is separation-free, portable, easy-to-fabricate, and low-cost, and may offer a platform for quantitative or qualitative analysis of other analytes in body fluids for POC applications.

Alginate/GelMA microparticles via oil-free interface shearing for untethered magnetic microbots.

Microrobots hold broad application prospects in the field of precision medicine, such as intravenous drug injection, tumor resection, opening blood vessels and imaging during abdominal surgery. However, the rapid and controllable preparation of biocompatible hydrogel microparticles still poses challenges. This study proposes the one-step direct acquisition of biocompatible sodium alginate and gelatin methacrylate (GelMA) hydrogel microparticles using an oil-free aqueous solution, ensuring production with a controllable generation frequency. An adaptive interface shearing platform is established to fabricate alginate/GelMA microparticles using a mixture of the hydrogel, photoinitiator, and Fe3O4 nanoparticles (NPs). By adjusting the static magnetic field intensity (Bs), vibration frequency, and flow rate (Q) of the dispersed phase, the size and morphology of the hydrogel microparticles can be controlled. These hydrogel microparticle robots exhibit magnetic responsiveness, demonstrating precise rotating and rolling movements under the influence of an externally rotating magnetic field (RMF). Moreover, hydrogel microparticle robots with a specific critical frequency (Cf) can be customized by adjusting the Bs and the concentration of Fe3O4 NPs. The directional in situ untethered motion of the hydrogel microparticle robots can be successfully realized and accurately controlled in the climbing over obstacles and in vitro experiments of animals, respectively. This versatile and fully biodegradable microrobot has the potential to precisely control movement to bone tissue and the natural cavity of the human body, as well as drug delivery.

A novel strategy to construct hydrogels with anti-swelling and water-retention abilities by covalent surface modification.

Hydrogels have been widely used in various fields due to their diverse properties and flexible preparation methods. However, limited by the open network structure, hydrogels inevitably lose water in air or absorb water in aqueous solution, resulting in the loss of intrinsic functions, which severely hinders their practical applications. To address this issue, a general strategy was developed by subsequently modifying the surface of hydrogels with branched polyethyleneimine (PEI) and (3-(methacryloxy)propyl)trimethoxysilane (MPS) to covalently construct a dense cross-linked siloxane layer on the hydrogel surface. As a proof of concept, poly(2-(dimethylamino)ethyl methacrylate)/sodium alginate (PDMAEMA/SA) hydrogels were chosen as the model hydrogels to verify the feasibility of this strategy. The hydrogels adsorbed PEI to form amino-rich surfaces through hydrogen bonding, followed by covalently grafting MPS through rapid and catalyst-free mutual chemical reactions between acrylates and amine groups, as well as the hydrolysis of MPS. After modification, robust hydrophobic surfaces were successfully fabricated on the hydrophilic hydrogels. The modified hydrogels exhibited extraordinary anti-swelling and water-retention abilities. As the most typical intrinsic properties of hydrogels, the conductivity and sensing performance were well preserved. The strategy reported here provides a new insight into the construction of hydrogels with anti-swelling and water-retention abilities.

Effect of CO2 release behavior on the crosslinking degree of alginate hydrogels prepared with CaCO3 and carbonated water

The CO2 release behavior, i.e., “post-gelation condition,” affects the degree of cross-linking, an essential parameter for determining hydrogel properties.

Breathable polyvinyl alcohol reinforced sodium alginate hydrogel fiber knitted fabric containing curcumin as wound dressing for real-time pH monitoring

Due to the shortcomings of traditional medical dressings, the development of new dressings has become a hot topic. However, the mechanical properties of hydrogel fibers are relatively poor, so they are rarely spun and knitted, and tend to be in the state of sheet gels or laminated with fabrics as dressings. In this study, a novel fiber-type medical dressing with excellent biocompatibility, pH-monitoring function, drug slow-release effect, and fluid-absorbing ability was created using sodium alginate (SA), polyvinyl alcohol (PVA), and curcumin (CUR) based on wet spinning technology and weft-knitting technique. The X-ray diffraction and the tensile tests demonstrated that PVA could enhance the crystallinity and the tensile properties of the fiber, facilitating the formation of fabrics. In addition, CUR gave the dressing the ability to monitor wound pH in real-time. Moreover, the tests indicated that the SA/PVA/CUR hydrogel fiber fabrics studied in this paper have good swelling properties, drug retardation function, air permeability, moisture permeability, and bio-tissue compatibility, thus demonstrating the potential of this SA/PVA/CUR hydrogel fiber fabrics as medical dressings.

Design and fabrication of alginate hydrogel nanohybrid as a promising cancer treatment.

Basal cell carcinoma (BCC) is the most common form of skin cancer and the most frequently occurring form of all cancers, affecting sun-exposed areas like the face. Surgery is the main treatment, focusing on safe and minimally invasive methods for better outcomes. Technology has enabled the development of artificial skin substitutes for tissue repair. Tissue engineering uses scaffolds to create functional replacements. This project aims to create an alginate-based hydrogel with PEG-coated gold nanoparticles. The project extensively explored the modification of alginate hydrogels with PEG-coated gold nanoparticles, involving the synthesis of gold nanoparticles, their integration with the polymer, and the subsequent preparation of the concentrated hybrid hydrogel. Utilizing various physicochemical techniques, such as UV-visible spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy, the fabrication process was optimized and characterized. The successful synthesis of the hybrid biomaterial was achieved through robust and highly reproducible methods. The MTT assay results offered valuable insights into the biocompatibility and safety of the PEG-coated gold nanoparticle-loaded alginate-based films. The incorporation of PEG-coated gold nanoparticles allowed for potential drug loading on the nanoparticle surface and, consequently, within the hydrogel. Cellular assays were conducted to assess the potential applications of this novel biomaterial. The addition of polyethylene glycol made it possible to load different drugs onto the gold nanoparticles and also within the hydrogel. This makes it a promising choice for potential uses in tissue engineering.