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Bacterial infections and inflammation progression yield huge trouble for the management of serious skin wounds and burns. However, some hydrogel dressing exhibit poor wound-healing capabilities. Additionally, little information is given on the molecular theory of hydrogel gelation mechanisms and drug release performance from drug-polymer network in the water environment. Herein, cationic guar gum (CG) is first mixed with dipotassium glycyrrhizinate (DG), and then crosslinked Cu2+ to strengthen the mechanical strength followed by encapsulating mussel adhesive protein (MAP) as composite dressings. Intriguingly, CG-Cu2+ 0.5-DG10 possessed proper rheological properties and mechanical strength predominantly driven by strong CG-H2O-Cu2+ and Cu2+-CG hydrogen bonding interaction. Weak DG-CG hydrogen bonding only controlled DG release in the initial 4 h, while strong hydrogen bonding is the main force regulating the sustained release of Cu2+ within 48 h. The incorporation of MAP further loosened the tight crosslinking of CG-Cu2+ 0.5-DG10. The screened CG-Cu2+ 0.5-DG10/MAP possessed excellent self-healing, injectability, antibacterial, anti-inflammatory, cell proliferation-promotion activities with high biocompatibility. Therefore, CG-Cu2+ 0.5-DG10/MAP hydrogel expedited wound closure on S. aureus-infected full-thickness skin wound model and lowered necrosis progression to the unburned interspaces on a rat burn model. The results highlight the promising translational potential of Cu2+-inspired hydrogels for the management of burns and infected wounds.
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Cobre , Hidrogéis , Ligação de Hidrogênio , Cicatrização , Hidrogéis/química , Cobre/química , Animais , Cicatrização/efeitos dos fármacos , Liberação Controlada de Fármacos , Galactanos/química , Antibacterianos/farmacologia , Antibacterianos/química , Íons , Gomas Vegetais/química , Mananas/química , Ratos , Preparações de Ação Retardada/química , Ácido Glicirrízico/química , Ácido Glicirrízico/farmacologiaRESUMO
The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen-alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.
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Alginatos , Colágeno , Géis , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Degeneração Retiniana , Animais , Coelhos , Alginatos/química , Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Degeneração Retiniana/tratamento farmacológico , Doxiciclina/farmacologia , Doxiciclina/administração & dosagem , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Iodatos/toxicidade , Iodatos/administração & dosagem , Apoptose/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.
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Fluoruracila , Ouro , Hidrogéis , Nanopartículas Metálicas , Fotoquimioterapia , Ouro/química , Hidrogéis/química , Fluoruracila/farmacologia , Fluoruracila/química , Animais , Nanopartículas Metálicas/química , Camundongos , Humanos , Fotoquimioterapia/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Linhagem Celular Tumoral , Carboximetilcelulose Sódica/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Liberação Controlada de Fármacos , Terapia Fototérmica/métodosRESUMO
Porous metal-organic framework (MOF) liquids with permanent porosity, good fluidity, and fine dispersion attract broad attention in catalysis, transportation, gas storage, and chemical separations. Yet, the design and synthesis of porous MOF liquids for drug delivery remain less explored. Herein, a simple and general strategy is reported to prepare ZIF-91 porous liquid (ZIF-91-PL) via surface modification and ion exchange. The cationic nature of ZIF-91-PL not only renders it antibacterial but also with high curcumin loading capacity and sustained release. More importantly, the acrylate group on the grafted side chain of ZIF-91-PL makes it feasible to crosslink with modified gelatin through light curing, and the obtained hydrogel shows a significantly improved healing effect on the wound of diabetes. This work demonstrates for the first time, a MOF-based porous liquid for drug delivery, and the further fabrication of composite hydrogel may have potential applications in biomedical science.
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Diabetes Mellitus , Estruturas Metalorgânicas , Humanos , Porosidade , Estruturas Metalorgânicas/química , Bandagens , Cicatrização , Hidrogéis/farmacologiaRESUMO
MAIN CONCLUSION: Alginate/wastepaper hydrogel mitigated sunflower drought stress by increasing the water holding capacity of the soil and decreasing phosphate leaching. The hydrogel promoted sunflower growth and decreased stress related biomarkers. There is a growing interest in the development of biodegradable hydrogels for the alleviation of drought stress on plants. A novel hydrogel based on brown algal-derived alginate and wastepaper was developed and tested as a soil supplement for sunflower growth under moderate (75% field capacity (FC)) and extreme (50% FC) water-deficit stress. The hydrogel showed fast swelling in water, which obeyed the pseudo-first order kinetics. Besides, it increased the water holding capacity of the soil and exhibited a good phosphate adsorption (37 mg PO4- g-1 hydrogel after 6 days) in the soil, and more than 67% of the adsorbed phosphate was desorbed after 20 days. Thus, the phosphate leaching from the hydrogel-amended soil in a column experiment was only 2.77 mg after 4 times of over-irrigation, compared to 11.91 mg without the hydrogel. The hydrogel application promoted various root traits such as fresh and dry biomass, area, and length by > 2-, > 1.6-, > 1.35-, and > 1.3-folds under both water regimes in relation to the no-hydrogel treatments at the same conditions. Furthermore, the sunflower shoots exhibited similar proline contents to the well-watered control (100% FC), with > 50% reduction in relation to the drought-stressed plants under the same conditions. Similarly, the malondialdehyde contents were lowered by > 15%. The analysis of the antioxidant enzymes also indicated a marked reduction in the specific activities of catalase and ascorbate peroxidase under both 75 and 50% FC compared to the respective controls. Additionally, the hydrogel promoted the uptake of phosphate by sunflower roots. These results implied that the developed biodegradable hydrogel could be effectively applied as a soil additive to alleviate drought stress on crops.
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Helianthus , Raízes de Plantas , Secas , Hidrogéis , Alginatos , Solo , Desidratação , Água , FosfatosRESUMO
OBJECTIVE: This study aims to investigate the mechanism by which biomimetic composite hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) derived microRNA-19b-3p/WWP1 axis through extracellular vesicles (EVs) affect the new bone formation in rat bone defects. METHODS: First, synthesize the bionic composite hydrogel Gel-OCS/MBGN. Characterize it through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and FTIR. Then, conduct performance tests such as rheology, dynamic mechanical analysis, in vitro mineralization, and degradation. Rat BMSCs were selected for in vitro cell experiments, and EVs derived from BMSCs were obtained by differential centrifugation. The EVs were loaded onto Gel-OCS/MBGN to obtain Gel-OCS/MBGN@EVs hydrogel. Cell viability and proliferation were detected by live/dead cell staining and CCK-8 assay, respectively. ALP and ARS staining was used to evaluate the osteogenic differentiation of BMSCs. Differential gene expression analysis of osteogenic differentiation was performed using high-throughput sequencing. TargetScan database predicted the binding site between miR-19b-3p and WWP1, and a dual-luciferase reporter assay was performed to confirm the targeting binding site. A rat bone defect model was established, and new bone formation was evaluated by Micro-CT, H&E staining, and Masson's trichrome staining. Immunofluorescence staining and immunohistochemistry were used to detect the expression levels of osteogenic-related factors in rat BMSCs. RT-qPCR and Western blot were used to detect the expression levels of genes and proteins in tissues and cells. RESULT: Gel-OCS/MBGN was successfully constructed and loaded with EVs, resulting in Gel-OCS/MBGN@EVs. The in vitro drug release experiment results show that Gel-OCS/MBGN could sustainably release EVs. Further experiments have shown that Gel-OCS/MBGN@EVs could significantly promote the differentiation of BMSCs into osteoblasts. Experiments have shown that WWP1 is a key factor in osteogenic differentiation and is regulated by miR-19b-3p. EVs promote osteogenic differentiation by suppressing WWP1 expression through the transmission of miR-19b-3p. In vivo animal experiments have demonstrated that Gel-OCS/MBGN@EVs significantly promote bone repair in rats with bone defects by regulating the miR-19b-3p/WWP1 signaling axis. CONCLUSION: Functional Gel-OCS/MBGN@EVs were obtained by constructing Gel-OCS/MBGN and loading EVs onto it. EVs could deliver miR-19b-3p to BMSCs, inhibit the expression of WWP1, and promote the osteogenic differentiation of BMSCs, ultimately promoting bone regeneration in rats with bone defects.
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Vesículas Extracelulares , MicroRNAs , Ratos , Animais , Osteogênese , Hidrogéis , Biomimética , MicroRNAs/metabolismo , Diferenciação Celular , Vesículas Extracelulares/metabolismo , Células CultivadasRESUMO
Numerous innovative advancements in dressing technology for wound healing have emerged. Among the various types of wound dressings available, hydrogel dressings, structured with a three-dimensional network and composed of predominantly hydrophilic components, are widely used for wound care due to their remarkable capacity to absorb abundant wound exudate, maintain a moisture environment, provide soothing and cooling effects, and mimic the extracellular matrix. Composite hydrogel dressings, one of the evolved dressings, address the limitations of traditional hydrogel dressings by incorporating additional components, including particles, fibers, fabrics, or foams, within the hydrogels, effectively promoting wound treatment and healing. The added elements enhance the features or add specific functionalities of the dressings, such as sensitivity to external factors, adhesiveness, mechanical strength, control over the release of therapeutic agents, antioxidant and antimicrobial properties, and tissue regeneration behavior. They can be categorized as natural or synthetic based on the origin of the main components of the hydrogel network. This review focuses on recent research on developing natural polysaccharide-based composite hydrogel wound dressings. It explores their preparation and composition, the reinforcement materials integrated into hydrogels, and therapeutic agents. Furthermore, it discusses their features and the specific types of wounds where applied.
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Anti-Infecciosos , Hidrogéis , Hidrogéis/farmacologia , Cicatrização , Curativos Hidrocoloides , Polissacarídeos/farmacologiaRESUMO
Biomaterial associated bacterial infections are indomitable to treatment due to the rise in antibiotic resistant strains, thereby triggering the need for new antibacterial agents. Herein, composite bactericidal hydrogels were formulated by incorporating silver nanotriangles (AgNTs) inside a hybrid polymer network of Gum Tragacanth/Sodium Alginate (GT/SA) hydrogels. Physico-chemical examination revealed robust mechanical strength, appreciable porosity and desirable in vitro enzymatic biodegradation of composite hydrogels. The antibacterial activity of AgNT-hydrogel was tested against planktonic and biofilm-forming Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. For all the strains, AgNT-hydrogel showed a dose-dependent decrease in bacterial growth. The addition of AgNT-hydrogels (40-80 mg ml-1) caused 87% inhibition of planktonic biomass and up to 74% reduction in biofilm formation. Overall, this study proposes a promising approach for designing antibacterial composite hydrogels to mitigate various forms of bacterial infection.
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Infecções Estafilocócicas , Tragacanto , Humanos , Prata/farmacologia , Prata/química , Hidrogéis/farmacologia , Hidrogéis/química , Tragacanto/química , Alginatos/farmacologia , Biofilmes , Bactérias , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Salecan (Sal) is a novel marine microbial polysaccharide. In the present research, Sal and soy protein isolate (SPI) were adopted to fabricate Sal-SPI composite hydrogel based on a stepwise process (thermal treatment and transglutaminase induction). The effect of Sal concentration on morphology, texture properties, and the microstructure of the hydrogel was evaluated. As Sal concentration varied from 0.4 to 0.6 wt%, hydrogel elasticity increased from 0.49 to 0.85 mm. Furthermore, the internal network structure of Sal-SPI composite hydrogel also became denser and more uniform as Sal concentration increased. Rheological studies showed that Sal-SPI elastic hydrogel formed under the gelation process. Additionally, FTIR and XRD results demonstrated that hydrogen bonds formed between Sal and SPI molecules, inferring the formation of the interpenetrating network structure. This research supplied a green and simple method to fabricate Sal-SPI double network hydrogels.
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Hidrogéis , beta-Glucanas , Hidrogéis/química , Proteínas de Soja/metabolismo , Transglutaminases/metabolismo , beta-Glucanas/químicaRESUMO
The aim of this study was to evaluate the effect of oat ß-glucan on the formation mechanism, microstructure and physicochemical properties of konjac glucomannan (KGM) composite hydrogel. The dynamic rheology results suggested that the addition of oat ß-glucan increased the viscoelastic modulus of the composite hydrogel, which was conducive to the formation of a stronger gel network. Gelling force experiments showed that hydrogen bonds and hydrophobic interactions participated in the formation of the gel network. Textural profile analysis results found that the amount of oat ß-glucan was positively correlated with the elasticity, cohesiveness and chewiness of the composite hydrogel. The water-holding capacity of the composite hydrogel was enhanced significantly after the addition of oat ß-glucan (p < 0.05), which was 18.3 times that of the KGM gel. The thermal stability of KGM gel was enhanced after the addition of oat ß-glucan with the increase in Tmax being approximately 30 °C. Consequently, a composite hydrogel based on KGM and oat ß-glucan was a strategy to overcome pure KGM gel shortcomings.
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Hidrogéis , beta-Glucanas , Hidrogéis/química , Mananas/química , Reologia , ElasticidadeRESUMO
Local administration of platelet-derived growth factor-BB (PGDF-BB) and bone morphogenetic protein-2 (BMP-2) in a sequential release manner could substantially promote bone healing. To achieve this goal, a delivery system that could sustain the release of PGDF-BB and BMP-2 by way of temporal separation was developed. One type of PGDF-BB-encapsulated alginate microsphere and another type of BMP-2-encapsulated microsphere with a core-shell structure were respectively produced using emulsification methods. These two types of microspheres were then embedded into chitosan/glycerophosphate hydrogel for constructing composite gels. Some of them were found to be injectable at ambient temperature and had thermo-sensitive features near physiological temperature and pH. The optimally formulated composite gels showed the ability to control the release of PGDF-BB and BMP-2 in a sequential fashion in which PDGF-BB was released earlier than BMP-2. In vitro release patterns indicated that the release rates could be significantly regulated by varying the embedded amount of the factor-encapsulated microspheres, which can in turn mediate the temporal separation release interval between PGDF-BB and BMP-2. The released PDGF-BB and BMP-2 were detected to be bioactive based on their respective effects on Balb/c 3T3 and C2C12 cells. These results suggest that the presently developed composite gels have the potential for bone repair by synergistically utilizing the early chemotactic effect of PDGF-BB and the subsequent osteogenic and angiogenic functions of PDGF-BB and BMP-2.
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Becaplermina/administração & dosagem , Quitosana/química , Hidrogéis/química , Proteínas Proto-Oncogênicas c-sis/administração & dosagem , Alginatos/química , Animais , Células 3T3 BALB , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Camundongos , Microesferas , Osteogênese/efeitos dos fármacos , Alicerces TeciduaisRESUMO
Constructing bio-based composite hydrogel materials are receiving much interest, while regulating the interactions of the hydrogel components and integrating functions for multi-application meet various challenges. Herein, composite hydrogels were prepared by cross-linking of poly-acrylamide (PAM) and poly-N-[3-(Dimethylamino) propyl] acrylamide (PDMAPAA), assisted by natural galactomannan (GM) regulation. Even distribution and compatibility of GM in the three-dimensional materials were proved by a series of chemical and morphological characterizations, which favored the improvement of mechanical properties (~80 kPa) and flexibility. Besides, the hydrogels were well-connected with double networks of noncovalent intermolecular hydrogen bonding interactions and hydrophobic interactions, in addition to covalent-linked polymers. Due to great amount of inner hydrogen bond linkages, the hydrogels present satisfying anti-swelling capabilities (<15 %), exhibiting high potential for application in water treatment. Meanwhile, abundant surface functional groups provided possibilities to form interactive layer with the various substrates surface, exhibiting highly adhesive properties. Significant dyes adsorption capabilities were revealed on the hydrogels according to the electrostatic attraction with Congo red and hydrogen bond interactions with Brilliant green respectively. Thus, the proposed composite hydrogels integrated multi-functions due to the tuning the surface groups and cross-linking interactions, which provided deeper understanding on bio-based materials on fields of water treatment and environmental protection.
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Corantes , Galactose , Hidrogéis , Mananas , Hidrogéis/química , Mananas/química , Galactose/análogos & derivados , Galactose/química , Corantes/química , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Ligação de Hidrogênio , Interações Hidrofóbicas e HidrofílicasRESUMO
In this study, different concentrations of sodium alginate were compounded with pectin and phycocyanin to co-prepare composite hydrogel spheres (HP-PC-SA 0.2â¯%, 0.6â¯%, 1.0â¯%, 1.4â¯%) to evaluate the potential of the composite hydrogel spheres for the application as phycocyanin delivery carriers. The hydrogel spheres' physicochemical properties and bioaccessibility were assessed through scanning electron microscopy, textural analysis, drug-carrying properties evaluation, and in vitro and in vivo controlled release analysis in the gastrointestinal environment. Results indicated that higher sodium alginate concentrations led to smaller pore sizes and denser networks on the surface of hydrogel spheres. The textural properties of hydrogel spheres improved, and their water-holding capacity increased from 93.01â¯% to 97.97â¯%. The HP-PC-SA (1.0â¯%) formulation achieved the highest encapsulation rate and drug loading capacity, at 96.87â¯% and 6.22â¯%, respectively. Within the gastrointestinal tract, the composite hydrogel's structure significantly enhanced and protected the phycocyanin's digestibility, achieving a bioaccessibility of up to 88.03â¯%. In conclusion, our findings offer new insights into improving functionality and the effective use of phycocyanin via pectin-based hydrogel spheres.
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Alginatos , Portadores de Fármacos , Hidrogéis , Pectinas , Ficocianina , Alginatos/química , Pectinas/química , Ficocianina/química , Hidrogéis/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Disponibilidade Biológica , AnimaisRESUMO
An important objective of researchers is to develop a perfect wound dressing that can effectively treat different kinds of wounds. Natural substances with beneficial qualities, such as plant extracts and biopolymers are an ideal aid for wound care. Hydrogels based on biopolymers offer a lot of promising applications for topical use and are biocompatible, hydrophilic and non-toxic. When employed alone or in conjunction with other active agents, herbal extracts have a great deal of use in the healing of wounds. This study comprises Ruellia tuberosa extract loaded with carboxymethyl cellulose and guar gum hydrogels that have potential anti-bacterial, antioxidant, anti-inflammatory and hemocompatibility. Using mouse fibroblast cells (L929), the MTT (3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) test was conducted to assess the biocompatibility. Furthermore, the scratch wound assay using the L929 fibroblast cell line of mouse was employed to assess the in vitro wound healing potential of the synthesised composite hydrogels.
Assuntos
Carboximetilcelulose Sódica , Galactanos , Hidrogéis , Mananas , Gomas Vegetais , Cicatrização , Gomas Vegetais/química , Hidrogéis/química , Carboximetilcelulose Sódica/química , Animais , Mananas/química , Mananas/farmacologia , Galactanos/química , Galactanos/farmacologia , Camundongos , Cicatrização/efeitos dos fármacos , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Fibroblastos/citologia , Antioxidantes/farmacologia , Antioxidantes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
The objective of this work is utilizing fly ash to synthesize tobermorite (TOB) with a higher specific surface area and layered structure, and incorporating it into the starch/acrylic acid network to boost the drought resistance, water retention and heavy metal adsorption properties. The water absorption and water retention performance and cadmium adsorption characteristics of tobermorite/leftover rice-based composite hydrogel (TOB@LR-CH) were evaluated by water absorption swelling test, soil evaporation test and batch adsorption experiment. By adjusting the addition of TOB and other synthesized conditions, the swelling property (from 114.80 g/g to 322.64 g/g), water retention (71.80 %, 144 h) and Cd2+ adsorption characteristics (up to 591.36 mg/g) were significantly enhanced. Adding a moderate amount of TOB (2 wt%) provided the most uniform tobermorite dispersion during synthesis, and TOB2@LR-CH exhibited the most stable three-dimensional network and highest proportion of effective TOB. The adsorption behavior of cadmium on TOB2@LR-CH was more consistent with the pseudo-second-order kinetics and Langmuir isotherm models. Additionally, the regeneration test results displayed that the adsorption removal rate of cadmium by TOB2@LR-CH adsorbent remained stable after 5 cycles. This study demonstrates that TOB@LR-CH has good water absorption and water retention potential in arid and semi-arid soils, and also has potential application prospects in remediating Cd(II)-contaminated soil.
Assuntos
Cádmio , Poluentes Químicos da Água , Cádmio/química , Hidrogéis , Água , Amido , Secas , Adsorção , Poluentes Químicos da Água/química , Cinética , SoloRESUMO
Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ß-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.
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Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca2+crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.
Assuntos
Alginatos , Proteína Morfogenética Óssea 2 , Proliferação de Células , Quitosana , Hidrogéis , Microesferas , Engenharia Tecidual , Quitosana/química , Quitosana/análogos & derivados , Animais , Camundongos , Hidrogéis/química , Proliferação de Células/efeitos dos fármacos , Alginatos/química , Proteína Morfogenética Óssea 2/metabolismo , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Força Compressiva , Tamanho da Partícula , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/citologia , Teste de Materiais , Matriz Extracelular/metabolismo , Linhagem Celular , Osteogênese/efeitos dos fármacos , Água/químicaRESUMO
Nowadays, the need to track fast-spreading infectious diseases has raised due to the recent COVID-19 disease pandemic. As a response, Wastewater-based Surveillance (WBS) has emerged as an early detection and disease tracking method for large populations that enables a comprehensive overview of public health allowing for a faster response from public health sector to prevent large outbreaks. The process to achieve WBS requires a highly intensive sampling strategy with either expensive equipment or trained personnel to continuously sample. The sampling problem can be addressed by passive sampler development. Chitosan-based hydrogels are recognized for their capability to sample and remove various contaminants from wastewater, including metals, dyes, pharmaceuticals, among others. However, chitosan-based hydrogels unique characteristics, can be exploited to develop passive samplers of genetic material that can be a very valuable tool for WBS. This study aimed to develop a novel chitosan hydrogel formulation with enhanced characteristics suitable for use as a passive sampler of genetic material and its application to detect disease-causing pathogens present in wastewater. The study evaluates the effect of the concentration of different components on the formulation of a Chitosan composite hydrogel (Chitosan, Glutaraldehyde, Microcrystalline cellulose (MCC), and Polyethylene glycol (PEG)) on the hydrogel properties using a Box Hunter & Hunter experimental matrix. Hydrogels' weight, thickness, swelling ratio, microscopic morphology (SEM), FTIR assay, and zeta potential were characterized. The resulting hydrogel formulations were shown to be highly porous, positively charged (Zeta potential up to 35.80 ± 1.44 mV at pH 3) and with high water swelling capacity (up to 703.89 ± 15.00 %). Based on the results, a formulation from experimental design was selected and then evaluated its capacity to adsorb genetic material from a control spiked water with Influenza A virus synthetic vector. The adsorption capacity of the selected formulation was 4157.04 ± 64.74 Gene Copies/mL of Influenza A virus synthetic vector. The developed hydrogel showed potential to be used as passive sampler for pathogen detection in wastewater. However, deeper research can be conducted to improve adsorption, desorption and extraction techniques of genetic material from chitosan-hydrogel matrices.
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Impact-protective materials are gaining importance because of the widespread occurrence of impact damage. Hydrogels have emerged as promising candidates owing to their lightweight and flexible nature. However, achieving soft impact-resistant hydrogels with exceptional stiffness, strength, and toughness remains a challenge. Inspired by the Bouligand structure found in the smasher dactyl club of stomatopods, we propose a straightforward multiscale hierarchical structural design strategy. This strategy integrates self-assembly and salting-out techniques to enhance the impact resistance of soft hydrogels. Rigid cellulose nanocrystals (CNCs) self-assemble into Bouligand-like structures within soft poly(vinyl alcohol) (PVA) matrix via supramolecular interactions. This rational structural design combines the CNC Bouligand structure with a cross-linked network of soft PVA crystalline domains, resulting in a composite hydrogel with impressive mechanical properties: high tensile fracture strength (30.2 MPa), elastic modulus (62.7 MPa), and fracture energy (75.6 kJ m-2), surpassing those of other tough hydrogels. Moreover, the multiscale hierarchical structure facilitates various energy dissipation mechanisms, including crack twisting, tortuous crack paths, and PVA chain orientation, resulting in notable force attenuation (80.4%) in the composite hydrogel. This biomimetic design strategy opens new avenues for developing soft and lightweight impact-resistant materials.
RESUMO
Bone is a complex organic-inorganic composite tissue composed of â¼30% organics and â¼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.