Alginate Hydrogel Research Articles

Encapsulation of Mentha aquatica methanol extract in alginate hydrogel promotes wound healing in a murine model of Pseudomonas aeruginosa burn infection

Burn injuries are the fourth most prevalent devastating form of trauma worldwide. Among the most extensively explored materials, composite dressings with alginate loaded with herbal extract can be mentioned. This research aimed to develop a sodium alginate (SA)-based hydrogel encapsulated with Mentha aquatica (MA) methanol extract and investigate its therapeutic efficacy in the infected burn mouse model. SEM, FTIR, in vitro extract release, HPLC, mechanical test, contact angle, swelling, degradability, and temperature response properties were used to analyze the hydrogel scaffold's physicochemical structure. Additionally, the antibacterial activity and MIC level of the extract, cell cytotoxicity, and macroscopic and microscopic analysis of the wound healing process were done using Masson's trichrome and hematoxylin-eosin staining. The physicochemical properties of the SA hydrogel encapsulated with MA extract were verified. The lowest inhibitory dose of the extract was determined to be 12.5 mg/ml. Application of SA/MA hydrogel to localized wounds of deep third-degree burns demonstrated faster tissue regeneration, collagen recovery, and eradication of bacterial infection. This research focused on the design and the preparation of a novel and effective biomaterials-based medical product, which has the potential to rehabilitate infected and injured skin tissue; therefore, it can be a promising candidate for wound dressing applications.

Hydrogel and Microgel Collaboration for Spatiotemporal Delivery of Biofactors to Awaken Nucleus Pulposus‐Derived Stem Cells for Endogenous Repair of Disc

AbstractDepletion of nucleus pulposus‐derived stem cells (NPSCs) is a major contributing factor to the attenuation of endogenous regenerative capacity in intervertebral disc degeneration (IVDD). Introducing a hydrogel drug delivery system is a potential strategy for counteracting endogenous cell depletion. The present study proposes a delivery platform for the spatiotemporal release of multiple drugs by combining sodium alginate hydrogels with gelatin microgels (SCGP hydrogels). The SCGP hydrogels facilitated the initial release of chondroitin sulfate (ChS) and the gradual release of an independently developed parathyroid hormone‐related peptide (P2). The combined action of these two small molecule drugs “awakened” the reserve NPSCs, mitigated cell damage induced by H2O2, significantly enhanced their biological activity, and promoted their differentiation toward nucleus pulposus cells. The mechanical and viscoelastic properties of the hydrogel are enhanced by physical and chemical dual cross‐linking to adapt to the loading environment of the degenerated disc. A rat IVDD model is used to validate that the SCGP hydrogel can significantly inhibit the progression of IVDD and stimulate the endogenous repair of IVDD. Therefore, the spatiotemporal differential drug delivery system of the SCGP hydrogel holds promise as a convenient and efficacious therapeutic strategy for minimally invasive IVDD treatment.

Conductive, sensitivity, flexibility, anti-freezing and anti-drying silica/carbon nanotubes/sodium ions modified sodium alginate hydrogels for wearable strain sensing applications

The biocompatibility and salient gelling feature of alginate via forming the interpenetrating network structure has received extensive interests for different applications. Traditional alginate hydrogels freeze at low temperature and evaporate easily at room temperature, leading to reduced performance. Consequently, it is crucial to develop methods to prevent alginate hydrogel from freezing at subzero temperature and dehydration at normal temperature to maintain the performance stability. Utilizing polyacrylic acid, sodium alginate, and acrylamide-hydroxyethyl methacrylate copolymers as flexible matrix materials, this study develops a wearable silica (SiO2)/carbon nanotubes (CNT)/sodium ions (SiO2/CNT/Na+) modified sodium alginate hydrogel strain sensor characterized by high sensitivity, flexibility, and anti-freezing and anti-drying properties. The hydrogel doped with NaCl (50 mg), CNT (10 mg) and M-SiO2 (200 mg) shows excellent mechanical and electrical properties, the tensile strength is 436 KPa, the break elongation is 426 %, the elastic modulus is 99 KPa, and the toughness is 897 kJ/m3. The modified sodium alginate hydrogel used as strain sensor shows fast response time (∼100 ms), high sensitivity factor and excellent stability. The strain sensor exhibits excellent flexibility, ductility, self-adhesion, anti-freezing and anti-drying properties, significantly enhancing its strain sensing application field.

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

Multilayered alginate–hydrogel-functionalized zeolite based on ionic cross-linking composed with a certain Ca2+ and Mg2+ ratio for ammonium adsorption

To enhance ammonium removal in wastewater treatment, a novel adsorbent, multilayered ionic cross–linked alginate–hydrogel–metal-coated zeolite (Al-H-M-Z), was synthesized. Essential divalent cations, 2.60 mmol of Ca2+ and Mg2+, were incorporated into Al-H-M-Z (10 g) in a Ca2+:Mg2+ ratio of 0.73:1.85, facilitating strong alginate–polymer interactions and significantly enhancing the adsorption efficiency. Langmuir and Freundlich isotherm analyses revealed that Al-H-M-Z had a maximum adsorption capacity of 56.5 ± 8.78 mg g−1 and an adsorption intensity of 0.703 ± 0.122, which were 7.24-fold and 1.59-fold higher than those of natural zeolite (7.80 ± 1.09 mg g−1 and 0.444 ± 0.254), respectively. These enhanced properties are attributed to the modified structural and surface chemistry. The Al-H-M-Z coating exhibited a 4.76-fold increase in surface area (3.91 m2 g−1), an 8.94-fold increase in micropore volume (17.8 × 10−3 cm3 g−1), and a 4.22-fold increase in pore diameter (4.14 nm) when compared to the traditional Al-only coating. For applicability, Al-H-M-Z and Z achieved ammonium removal rates of 7.94% and 5.61%, respectively, in actual fish farm wastewater, representing a 1.41-fold improvement in adsorption efficiency after the coating process.

Colonic long-term retention and colonization of probiotics by double-layer chitosan/tannic acid coating and microsphere embedding for treatment of ulcerative colitis and radiation enteritis

Oral probiotics can alleviate enteric inflammations but their rapid transit through the gut limits their retention and colonization in the colon. Here, a novel strategy integrating the bacterial double-layer coating and hydrogel microsphere embedding techniques was used to highly enhance the colonic retention and colonization efficiency of Lactobacillus rhamnosus GG (LGG). LGG was coated by the double layers of chitosan (CS) and tannic acid (TA), and then embedded in calcium alginate (CA) hydrogel microspheres to form LGG@CT@CA. The microspheres resisted gastric liquids, improving LGG safe transit through the stomach to reach the colon. LGG@CT was rapidly released in the colon due to the good swelling of hydrogel microspheres. More importantly, LGG exhibited long-term retention up to 7 days in the colon and colonized the deep site of the colonic mucosa. LGG@CT@CA had a high therapeutic efficiency of ulcer colitis with the long colon and the low intestinal permeability of colonic tissues. LGG@CT@CA also alleviated the small intestinal damage induced by irradiation and the survival rates were improved. The mechanisms included local ROS decrease, IL-10 increase, and ferroptosis reduction in the small intestine. The oral colon-targeted system holds promise for oral probiotic therapy by the long-term retention and colonization in the colon.

Effect of microplastic ingredient on the removal of microplastics by calcium alginate flocculation

The widespread presence of microplastics induce a serious threat to the survival of living organisms. Herein, calcium alginate hydrogel was selected as a flocculant to remove microplastics from water. To determine the variability of the flocculation method for the removal of microplastics with different properties, 11 microplastics of different sizes or components were used. The results showed the removal of different microplastics were 99.5% (PSMP 5 µm), 99.5% (24 h aged PSMP), 98.6% (72 h aged PSMP), 97.1% (48 h aged PSMP), 92.0% (PMMA 15 µm), 84.0% (PAMP 5 µm), 82.0% (PVCMP 1 µm), 80.2% (PLAMP 500 mesh), 68.0% (PEMP 100 mesh), 52.0% (PE 20 µm), and 52.0% (PP 1000 mesh). Microplastics were mainly wrapped and swept by flocs. The density and surface hydrophilicity of microplastics are the main reasons for the discrepancy in their removal efficiency. Calcium alginate also performed well in the removal of microplastics in natural water. When the initial concentration of the polystyrene microplastic suspension was 5 mg/L, the removal rates of microplastics in the five water samples were 99.60% (pipe water), 98.19% (lake water), 98.71% (river water), 100.44% (sludge supernatant), and 100.00% (seawater). Also, flocculation method could almost completely remove fibrous microplastics from washing wastewater. It is aim to provide reference data for the removal of different microplastics in water by flocculation, and also expect to increase the emphasis on microplastic variability in the future removal exploration.

Development of a zoledronate-modified functional alginate hydrogel with effects of promoting osteogenesis for potential osteoporosis treatment

Osteoporosis is one of the most prevalent age-related diseases worldwide. It is characterized by a systemic deterioration in bone strength (bone density and bone mass), leading to an increase in fragility fractures. The complex pathological environment of osteoporosis presents a significant challenge to the induction of bone regeneration under osteoporotic conditions. Therefore, the development of a system for local delivery of active substances with osteoinductive effects is of practical significance in the clinical treatment of osteoporosis. In this study, we successfully loaded the anti-osteoporotic small molecule drug zoledronate (ZOL) into calcium alginate to prepare a biologically functional hydrogel, designated as ALG-ZOL-Ca. The prepared ALG-ZOL-Ca hydrogel gels quickly, making the hydrogel easy to inject and adapt to irregularly shaped bone defects, and simultaneously exhibits good bioactivity and osteoconductivity. The RT-qPCR results suggested that this hydrogel effectively promoted the expression levels of β-catenin and Axin2, which indicating a stimulative effect on the Wnt/β-catenin pathway in vitro. Moreover, ALG-ZOL-Ca hydrogel effectively promoted the expression of the OCN and SP7 genes. Therefore, this study proposes a new functional composite hydrogel that provides a potential treatment strategy for osteoporosis.

Alginate-Based Hydrogel Bead Reinforced with Montmorillonite Clay and Bacterial Cellulose-Activated Carbon as an Effective Adsorbent for Removing Dye from Aqueous Solution.

According to environmental concerns related to water pollution, this study aims to develop a novel hydrogel bead as a biocompatible and efficient adsorbent by integrating bacterial cellulose-activated carbon (BCAC) and montmorillonite (MT) in alginate hydrogel (ALG). The ionotropic gelation method was applied to the fabrication of BCAC/MT/ALG hydrogel beads. The BCAC/MT/ALG hydrogel bead exhibited significantly higher tensile strength, Young's modulus, and thermal stability, with ~1.4 times higher adsorption uptake of methylene blue (MB) from aqueous solution as compared to the pristine ALG bead. The textural properties, including specific surface area and porosity, were beneficial to accommodate the size of cationic MB as the target molecule. This resulted in a remarkable MB adsorption uptake of 678.2 mg/g at pH 7 and 30 °C. The adsorption isotherm showed the best fit for the nonlinear Redlich-Peterson isotherm model. Experimental adsorption data were well-described by the pseudo-second order kinetic model, with R2 values reaching 0.997. In addition, the adsorbent bead demonstrated easy regeneration with high reusability with approximately 75% of MB removal after being used for six cycles. Therefore, BCAC/MT/ALG bead represents an eco-friendly, cost-effective, and highly efficient adsorbent for MB removal from water and could potentially be used for removal of a wide range of cationic dye pollutants from wastewater.

A novel injectable boron doped-mesoporous nano bioactive glass loaded-alginate composite hydrogel as a pulpotomy filling biomaterial for dentin regeneration

BackgroundDifferent materials have been used as wound dressings after vital pulp therapies. Some of them have limitations such as delayed setting, difficult administration, slight degree of cytotoxicity, crown discoloration and high cost. Therefore, to overcome these disadvantages, composite scaffolds have been used in regenerative dentistry. This study aims to construct and characterize the physicochemical behavior of a novel injectable alginate hydrogel loaded with different bioactive glass nanoparticles in various concentrations as a regenerative pulpotomy filling material.MethodsAlginate hydrogels were prepared by dissolving alginate powder in alcoholic distilled water containing mesoporous bioactive glass nanoparticles (MBG NPs) or boron-doped MBG NPs (BMBG NPs) at 10 and 20 wt% concentrations. The mixture was stirred and incubated overnight in a water bath at 50 0 C to ensure complete solubility. A sterile dual-syringe system was used to mix the alginate solution with 20 wt% calcium chloride solution, forming the hydrogel upon extrusion. Then, constructed hydrogel specimens from all groups were characterized by FTIR, SEM, water uptake percentage (WA%), bioactivity and ion release, and cytotoxicity. Statistical analysis was done using One-Way ANOVA test for comparisons between groups, followed by multiple pairwise comparisons using Bonferroni adjusted significance level (p < 0.05).ResultsAlginate/BMBG loaded groups exhibited remarkable increase in porosity and pore size diameter [IIB1 (168), IIB2 (183) (µm)]. Similarly, WA% increased (~ 800%) which was statistically significant (p < 0.05). Alginate/BMBG loaded groups exhibited the strongest bioactive capability displaying prominent clusters of hydroxyapatite precipitates on hydrogel surfaces. Ca/P ratio of precipitates in IIA2 and IIB1 (1.6) were like Ca/P ratio for stoichiometric pure hydroxyapatite (1.67). MTT assay data revealed that the cell viability % of human gingival fibroblast cells have declined with increasing the concentration of both powders and hydrogel extracts in all groups after 24 and 48 h but still higher than the accepted cell viability % of (˃70%).ConclusionsThe outstanding laboratory performance of the injectable alginate/BMBGNPs (20 wt%) composite hydrogel suggested it as promising candidate for pulpotomy filling material potentially enhancing dentin regeneration in clinical applications.

Chitosan/Sodium Alginate Hydrogel for the Release of Berberine as an Algae Suppressant: RSM Optimization and Analysis of Sustained Release Characteristics.

In this study, we used chitosan/sodium alginate hydrogel as a carrier to prepare berberine sustained-release capsule materials that can inhibit algae for a long time and safely. The preparation conditions of the material were optimized by the response surface method, and the optimized capsule material was characterized and the sustained release characteristics were analyzed to study the change of the algae inhibition effect of the material within 30 days. The results showed that the optimum preparation parameters of the material were 0.54% chitosan content, 2.46% sodium alginate content and 1.09% anhydrous calcium chloride content by response surface optimization design, which was consistent with the parameters set by each factor at the central point. The algae inhibition rate of the material under this preparation condition was 93.75 ± 1.01%, which was similar to the predicted value. The release characteristics analysis showed that the material continuously released up to 90% of berberine within 24 days, and its release characteristics were sustained release after burst release, with good sustained release effect. The results of material characterization showed that chitosan/sodium alginate hydrogel could effectively load berberine and was beneficial to the loading and release of berberine. The results of algae inhibition experiments showed that low concentration materials could control the outbreak of cyanobacterial blooms in a short time, while under high concentration conditions, the materials could inhibit Microcystis aeruginosa efficiently and for a long time.

Xyloglucan, alginate and k-carrageenan hydrogels on spheroids of adipose stem cells survival; preparation, mechanical characterization, morphological analysis and injectability

The therapeutic capabilities of autologous stem cells can be fully exploited if their survival after implantation is improved.For the first time, we compared three hydrogels, with different chemical structure, morphology, and viscoelastic properties, where the same differentiation factors were immobilized and spheroids from adipose stem cells (SASCs) were incorporated. The aim is to understand if hydrogel characteristics could influence the viability of the embedded stem cells. Specifically, hydrogels of partially degalactosylated xyloglucan (dXG), sodium alginate (Alg) and k-carrageenan (kC) were produced. The structure of the networks was probed by swelling/erosion measurements, rheological and morphological analysis. Cell viability was measured after 7 and 21 days. When SASCs were incubated under stemness conditions, dXG and kC hydrogels provide the optimal environment for cell viability. When incubated in the chondrogenic or osteogenic medium, a clear correlation was found between the storage and loss moduli and cell viability. Hydrogels with the lowest shear stiffness promote stem-cell differentiation and proliferation. The systems, particularly dXG, seem more similar to natural ECM and able to recreate niches, that colonized with stem cells could represent a real support in regenerative therapies. The injectability of formulations was evaluated to determine if they could be used for minimally invasive regenerative medicine interventions.

Ion pump-inspired biomimetic interfacial evaporation platform for simultaneous seawater desalination, uranium extraction, and electricity generation

To accelerate progress toward the Sustainable Development Goals (SDGs), here we develop an ion pump-inspired biomimetic interfacial evaporation platform (IBIP). Such an innovative platform integrates seawater desalination, electricity generation, and uranium extraction. A biochar-doped sodium alginate hydrogel is used to validate the IBIP’s efficacy. In long-term trials under 1 sun, IBIP maintains a stable evaporation rate of 1.80 kg m−2 h−1 and achieves a consistent uranium adsorption ratio exceeding 80 % within 48 h in real seawater. Additionally, the IBIP demonstrates an enhanced electricity output, with Voc and Isc reaching 0.9 V and 14.0 μA, respectively. By constructing a 3D structure, the IBIP’s performance under 1 sun significantly escalates to 4.3 kg m−2 h−1 for evaporation rate, 168.1 mg g−1 for uranium extraction capacity, and 1.02 V for Voc, respectively. In conclusion, this work offers a high-efficiency and eco-friendly way for the sustainable utilization of seawater resources.

Super-strain, high sensitivity, and multi-responsive flexible sensor based on nanocellulose hydrogels

The application of flexible sensors based on conductive hydrogels in human motion monitoring has been widely studied. Here, a facile one-pot method is proposed to prepare nanocellulose/polyacrylamide/sodium alginate hydrogel (CNWs/SA/PAM). The resulting CNWs/SA/PAM hydrogel has exceptional mechanical properties (7850 %, 1.3 MPa) and high sensitivity (14200 %, GF=3.6, 68 ms). The nanocellulose crystals (CNWs) are bent and entangled with the backbone of the polyacrylamide/sodium alginate (PAM/SA) hydrogel network, effectively transferring external mechanical forces to the entire physical and chemical cross-linking domains. This feature considerably improves the tensile strength, strain sensing range, and sensitivity of the hydrogel. The CNWs/SA/PAM hydrogel exhibits a sensitive response to water molecules and temperature-stimulated shape memory behaviour and can act as a programmable deformation actuator. The hydrogel sensor can detect and monitor subtle human motion signals in a timely and accurate manner. It is designed as a single-electrode friction nanogenerator insole (insole-TENG) that can monitor the large motion states of the human body in real time and can be efficiently used for small self-powered electronic devices. This study will shed some light on developing cellulose hydrogels in multifunctional human motion health detection sensors, soft-actuated robots, and self-powered applications for small electronic devices.

A 3D Bio-Printed-Based Model for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very poor prognosis, characterized by incidence rates very close to death rates. Despite the efforts of the scientific community, preclinical models that faithfully recreate the PDAC tumor microenvironment remain limited. Currently, the use of 3D bio-printing is an emerging and promising method for the development of cancer tumor models with reproducible heterogeneity and a precisely controlled structure. This study presents the development of a model using the extrusion 3D bio-printing technique. Initially, a model combining pancreatic cancer cells (Panc-1) and cancer-associated fibroblasts (CAFs) encapsulated in a sodium alginate and gelatin-based hydrogel to mimic the metastatic stage of PDAC was developed and comprehensively characterized. Subsequently, efforts were made to vascularize this model. This study demonstrates that the resulting tumors can maintain viability and proliferate, with cells self-organizing into aggregates with a heterogeneous composition. The utilization of 3D bio-printing in creating this tumor model opens avenues for reproducing tumor complexity in the future, offering a versatile platform for improving anti-cancer therapy models.

Gelatin-Sodium Alginate Hydrogels Cross-Linked by Squaric Acid and Dialdehyde Starch as a Potential Bio-Ink.

Hydrogels as biomaterials possess appropriate physicochemical and mechanical properties that enable the formation of a three-dimensional, stable structure used in tissue engineering and 3D printing. The integrity of the hydrogel composition is due to the presence of covalent or noncovalent cross-linking bonds. Using various cross-linking methods and agents is crucial for adjusting the properties of the hydrogel to specific biomedical applications, e.g., for direct bioprinting. The research subject was mixtures of gel-forming polymers: sodium alginate and gelatin. The polymers were cross-linked ionically with the addition of CaCl2 solutions of various concentrations (10%, 5%, 2.5%, and 1%) and covalently using squaric acid (SQ) and dialdehyde starch (DAS). Initially, the polymer mixture's composition and the hydrogel cross-linking procedure were determined. The obtained materials were characterized by mechanical property tests, swelling degree, FTIR, SEM, thermal analysis, and biological research. It was found that the tensile strength of hydrogels cross-linked with 1% and 2.5% CaCl2 solutions was higher than after using a 10% solution (130 kPa and 80 kPa, respectively), and at the same time, the elongation at break increased (to 75%), and the stiffness decreased (Young Modulus is 169 kPa and 104 kPa, respectively). Moreover, lowering the concentration of the CaCl2 solution from 10% to 1% reduced the final material's toxicity. The hydrogels cross-linked with 1% CaCl2 showed lower degradation temperatures and higher weight losses than those cross-linked with 2.5% CaCl2 and therefore were less thermally stable. Additional cross-linking using SQ and DAS had only a minor effect on the strength of the hydrogels, but especially the use of 1% DAS increased the material's elasticity. All tested hydrogels possess a 3D porous structure, with pores of irregular shape and heterogenic size, and their swelling degree initially increased sharply to the value of approx. 1000% during the first 6 h, and finally, it stabilized at a level of 1200-1600% after 24 h. The viscosity of 6% gelatin and 2% alginate solutions with and without cross-linking agents was similar, and they were only slightly shear-thinning. It was concluded that a mixture containing 2% sodium alginate and 6% gelatin presented optimal properties after gel formation and lowering the concentration of the CaCl2 solution to 1% improved the hydrogel's biocompatibility and positively influenced the cross-linking efficiency. Moreover, chemical cross-linking by DAS or SQ additionally improved the final hydrogel's properties and the mixture's printability. In conclusion, among the tested systems, the cross-linking of 6% gelatin-2% alginate mixtures by 1% DAS addition and 1% CaCl2 solution is optimal for tissue engineering applications and potentially suitable for 3D printing.

Tunable Hybrid Hydrogels of Alginate and Cell-Derived dECM to Study the Impact of Matrix Alterations on Epithelial-to-Mesenchymal Transition.

Epithelial-to-mesenchymal transition (EMT) is crucial for tumor progression, being linked to alterations in the extracellular matrix (ECM). Understanding the ECM's role in EMT can uncover new therapeutic targets, yet replicating these interactions in vitro remains challenging. It is shown that hybrid hydrogels of alginate (ALG) and cell-derived decellularized ECM (dECM), with independently tunable composition and stiffness, are useful 3D-models to explore the impact of the breast tumor matrix on EMT. Soft RGD-ALG hydrogels (200Pa), used as neutral bulk material, supported mammary epithelial cells morphogenesis without spontaneous EMT, allowing to define the gene, protein, and biochemical profiles of cells at different TGFβ1-induced EMT states. To mimic the breast tumor composition, dECM from TGFβ1-activated fibroblasts (adECM) are generated, which shows upregulation of tumor-associated proteins compared to ndECM from normal fibroblasts. Using hybrid adECM-ALG hydrogels, it is shown that the presence of adECM induces partial EMT in normal epithelial cells, and amplifes TGF-β1 effects compared to ALG and ndECM-ALG. Increasing the hydrogel stiffness to tumor-like levels (2.5kPa) have a synergistic effect, promoting a more evident EMT. These findings shed light on the complex interplay between matrix composition and stiffness in EMT, underscoring the utility of dECM-ALG hydrogels as a valuable in vitro platform for cancer research.

CHEMICAL MODIFICATION AND BIOLOGICAL ACTIVITY OF ALGINATE-BASED HYDROGELS

In recent years, the problem of wound infection has risen dramatically. Infectious complications of surgical wounds have increased significantly, often leading to severe sepsis. Gram-negative bacteria and microorganisms, which are immune to virtually all currently available antimicrobials, are the main culprits. In this regard, the development and implementation of innovative drugs and wound dressings, purulent and chronic wound treatment methods is an urgent problem of many domestic and foreign researchers. Brown algae are extracted using an alkaline solution to produce the ionic polysaccharide sodium alginate. It still holds one of the top positions among water-soluble polymers of natural origin as a result of various highly useful practical characteristics. Based on alginate hydrogels, it is possible to create new materials for biotechnological, pharmaceutical and medical purposes, as they have high moisture retention capacity, non-toxicity and self-decomposing ability. After reviewing the literature, we concluded that cefepime is a new antibiotic researched for wound dressing using IV generation cephalosporins as an antibacterial agent. It is highly resistant to hydrolysis by most beta-lactamases and quickly penetrates the cells of gram-negative bacteria. Inside the bacterial cell, it targets penicillin-binding proteins. To obtain new derivatives of sodium alginate with special properties, a chemical method, in particular, thiolene reactions, was used. It should be noted that click chemistry refers to a set of chemical reactions for the rapid and reliable synthesis of compounds by the uniform addition of individual components. Thiolene reactions offer significant advantages, includingversatile reaction conditions (including radical reactions and catalytic processes) and the ability to use a wide range of substrates with different unsaturated bonds such as acrylates, methacrylates and ethers. To monitor the rate and efficiency of UV activation, we used a sol-gel assay technique that allowed us to quantify insoluble (spatially cross-linked) and soluble polymers. After UV activation, samples with different ratios of thiol derivative (S-H bond) showed low viscosity, indicating the predominant degradation of polymer molecules in these systems. Since alginate-polymer derivatives primarily exhibit deconstructive behavior, the dominant process in alginate molecules is the breaking of bonds rather than their formation. The size of the gel fraction reflects the efficiency of polymer cross-linking, which in turn affects the efficiency of immobilization of the drug in the hydrogel matrix and its release rate. This study presents an experimental characterization of photocrosslinked hydrogels aimed at evaluating and elucidating the physicochemical and biological properties of the antibiotic cefepime in an alginate polymer. The obtained kinetic parameters of the swelling-dissolving process show that the synthesized alginate hydrogel is capable of providing a diffused and prolonged release of drugs. In addition, the synthesized hydrogel effectively delivers cefepime to the tested bacterial strains, showing high antibacterial activity without toxicity. However, further in vivo studies are needed to evaluate the fate and toxicity of the alginate-based hydrogel before definitive conclusions can be drawn regarding the usefulness of the synthesized drugs. These preliminary results can be the basis for the development of medical products.

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.