Dextran Hydrogels Research Articles

Injectable gelatin/oxidized dextran hydrogel loaded with apocynin for skin tissue regeneration

Acute skin injury should be treated in time, due to many factors will affect the normal healing process of wounds, hinder tissue regeneration, and eventually form chronic wounds. Herein, an injectable, in-situ gel-forming hydrogel has been fabricated. The hydrogel is stabilized by dynamic Schiff base and composed of gelatin (Gel), oxidized dextran (Odex) and apocynin (Apo). In vitro studies have shown that this hydrogel has good injectability, plasticity, self-healing and efficient hemostatic properties. The hydrogel has good cytocompatibility with HaCaT and L929 cells by the Live/Dead cell staining. Furthermore, in vivo studies have shown that hydrogel loaded with APO can accelerate angiogenesis and skin tissue regeneration by reducing wound inflammation. Therefore, the injectable Gel/Odex/Apo hydrogel has the advantages of simple preparation process, convenient use and multifunction, etc., it is a promising wound dressing for full-thickness skin repair and has great potential in the field of skin tissue regeneration.

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery.

Stimuli‐responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis‐azide crosslinkers that are used to prepare transparent self‐supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π‐extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein‐loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov‐triggered release is as yet inconclusive due to unexpected side‐reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.

Synthesis of Magnetic/pH Dual Responsive Dextran Hydrogels as Stimuli-Sensitive Drug Carriers

Synthesis of Magnetic/pH Dual Responsive Dextran Hydrogels as Stimuli-Sensitive Drug Carriers

Macroporous Dextran Hydrogels for Controlled Growth Factor Capture and Delivery Using Coiled-Coil Interactions

Macroporous Dextran Hydrogels for Controlled Growth Factor Capture and Delivery Using Coiled-Coil Interactions

Dextran and peptide-based pH-sensitive hydrogel boosts healing process in multidrug-resistant bacteria-infected wounds

Traumatic multidrug-resistant (MDR) bacterial infections are deadly threat to the public. To combat MDR bacteria, we developed a dual functional pH-sensitive hydrogel based on peptide DP7 (VQWRIRVAVIRK) and oxidized dextran (DP7-ODEX hydrogel). As an antimicrobial peptide, DP7 can synergize with many antibiotics; thus, we loaded ceftazidime into DP7-ODEX hydrogel, which showed an obvious advantage in MDR P. aeruginosa inhibition. Additionally, due to the interaction between aldehyde groups in oxidized dextran and amine groups from wound tissue, the hydrogel could extend on the irregular surface of skin defects and promote epithelial cells adhesion. DP7 could also be used as a wound-healing peptide and accelerate the healing process. We confirmed that the DP7-ODEX hydrogel exerted formidable therapeutic effects in normal or diabetic wound infection model. According to histomorphology analysis we found that DP7 hydrogel also have a scarless wound healing ability. In summary, we developed a hydrogel fabricated by the dual functional peptide DP7 that can kill multidrug-resistant bacteria colonizing the wound bed and boost scarless wound healing.

Gamma Radiation Induced Contraction of Alkyne Modified Polymer Hydrogels

AbstractGamma radiation triggered secondary crosslinking of dextran hydrogels leads to macroscopic hydrogel contraction. The authors use stable polymer hydrogels, prepared through azide‐alkyne crosslinking, containing surplus alkyne groups. γ‐irradiation of these gels leads to more alkyne crosslinking, enabling controlled increase of crosslink density, which in turn leads to an increase of hydrogel stiffness and macroscopic hydrogel contraction. Gel contraction scales linearly with the applied radiation dose. The same mechanism is applied to achieve γ‐radiation triggered release of the small molecule cargo, akin to wringing out a sponge. γ‐irradiation of touching hydrogel objects leads to gel fusion and the formation of a self‐supporting gel connection, demonstrating the reactivity of the excess alkyne groups. They envision applications in gel gluing and the construction of complex gel architectures, as well as in responsive materials for controlled release.

Biological and bioactivity assessment of dextran nanocomposite hydrogel for bone regeneration.

Insufficient biological and bioactive properties of dextran hydrogels limit their applications as promising scaffolds for tissue engineering. We developed nanocomposite dextran hydrogels comprised of bioactive glass (nBGC: 64% SiO2, 31% CaO, 5% P2O5) nanoparticles with an average particle size of 77nm using a chemical crosslinking of dextran chains to form 3D hydrogel networks. In the current study; bioactivity of the obtained nanocomposite hydrogels was evaluated through the formation of apatite crystal structures after the incubation in simulated body fluid (SBF) at various submersion periods and nBGC content. The scanning electron microscopy (SEM) micrographs represented an enhanced hydroxyapatite formation on the cross section of nanocomposite comprising of nBGC content from 2 to 8 (% by wt). Biomineralization results of Dex-8 (% by wt) composite during 7, 14 and 28days immersion indicated the apatite layer formation and the growth of apatite crystal size on the surface and cross section of the nanocomposite. Moreover, MTT assessments indicated that human osteosarcoma cells (SaOS-2) were able to adhere and spread within the dextran hydrogels reinforced with the bioactive glass nanoparticles. With regard to enhanced bioactivity and biocompatibility, the developed dextran-nBGC hydrogel could be considered as a suitable candidate for bone tissue engineering application.

Cell Migration Regulated by Spatially Controlled Stiffness inside Composition‐Tunable Three‐Dimensional Dextran Hydrogels

AbstractStiffness of the extracellular matrix plays an important role in regulating cell migration. In this paper, two types of 3D dextran hydrogel, with the stiffness distributed homogeneously and heterogeneously in subcellular scales, have been designed and fabricated to serve as macromolecule scaffolds in which C2C12 cells, an immortalized mouse myoblast cell line, can migrate in a rationally controllable manner. The experimental results indicate that heterogeneous gels can support higher migration velocities, and effective supporting time‐stage for enhancing migration depended on the bulk stiffness that can be rationally and elaborately tuned. Moreover, migration velocity for both types of gels, in most cases, tends to decrease first and then increase from day 0 to day 6. These results show advantages for regulation of cell migration using this easy‐to‐implement heterogeneous cross‐linking approach. Further, associated principles regarding the relationship among cell migration, gel stiffness distribution, and expression of F‐actin and myosin II are also discussed. These studies support rational control of cell migration velocity in heterogeneously cross‐linked hydrogels that are widely applicable in biomaterial field.

Mineralization of 3D Osteogenic Model Based on Gelatin-Dextran Hybrid Hydrogel Scaffold Bioengineered with Mesenchymal Stromal Cells: A Multiparametric Evaluation.

Gelatin–dextran hydrogel scaffolds (G-PEG-Dx) were evaluated for their ability to activate the bone marrow human mesenchymal stromal cells (BM-hMSCs) towards mineralization. G-PEG-Dx1 and G-PEG-Dx2, with identical composition but different architecture, were seeded with BM-hMSCs in presence of fetal bovine serum or human platelet lysate (hPL) with or without osteogenic medium. G-PEG-Dx1, characterized by a lower degree of crosslinking and larger pores, was able to induce a better cell colonization than G-PEG-Dx2. At day 28, G-PEG-Dx2, with hPL and osteogenic factors, was more efficient than G-PEG-Dx1 in inducing mineralization. Scanning electron microscopy (SEM) and Raman spectroscopy showed that extracellular matrix produced by BM-hMSCs and calcium-positive mineralization were present along the backbone of the G-PEG-Dx2, even though it was colonized to a lesser degree by hMSCs than G-PEG-Dx1. These findings were confirmed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), detecting distinct lipidomic signatures that were associated with the different degree of scaffold mineralization. Our data show that the architecture and morphology of G-PEG-Dx2 is determinant and better than that of G-PEG-Dx1 in promoting a faster mineralization, suggesting a more favorable and active role for improving bone repair.

Interference-free photoelectrochemical immunoassays using carboxymethylated dextran-coated and gold-modified TiO2 nanotube arrays.

An interference-free photoelectrochemical (PEC) immunoassay was developed for cardiac troponin I (cTnI) detection. Covalent linkage of cTnI antibody to carboxymethylated (CM-) dextran pre-immobilized onto a gold nanoparticles (AuNPs)-modified TiO2 nanotube array (NTA) affords five consecutive analyte captures with surface regenerations in between. Changes in the photocurrents at this photoanode before and after cTnI captures can be well fitted with the Langmuir isotherm from 0.220 pM to 2.20 nM cTnI. Owing to the inherently high sensitivity of the PEC detection, the detection limit (2.20 pg/mL) is lower than the range attainable with the enzyme-linked immunosorbent assay (ELISA) (6.00-40.0 pg/mL). Furthermore, CM-dextran prevents species in complex biological matrices from nonspecifically adsorbing onto the sensor surface, a feature not attainable with uncoated semiconductor electrodes or those coated with non-hydrogel-based chemical modifiers. The excellent anti-fouling property of dextran hydrogel allowed us to validate the accuracy of our regenerable sensors through a comparison of PEC immunoassays of patient sera to those of ELISA.

Ultrafast in-situ forming halloysite nanotube-doped chitosan/oxidized dextran hydrogels for hemostasis and wound repair

A series of halloysite nanotube (HNT)-doped chitosan (CS)/oxidized dextran (ODEX) adhesive hydrogels were developed through a Schiff base reaction. The resultant CS/ODEX/HNT hydrogels could not only form in situ on wounds within only 1 s when injected, but could also adapt to wounds of different shapes and depths after injection. We established four rat and rabbit hemorrhage models and demonstrated that the hydrogels are better than the clinically used gelatin sponge for reducing hemostatic time and blood loss, particularly in arterial and deep noncompressible bleeding wounds. Moreover, the natural antibacterial features of CS and ODEX provided the hydrogels with strong bacteria-killing effects. Consequently, they significantly promoted methicillin-resistant Staphylococcus aureus -infected-wound repair compared to commercial gelatin sponge and silver-alginate antibacterial wound dressing. Hence, our multifunctional hydrogels with facile preparation process and utilization procedure could potentially be used as first-aid biomaterials for rapid hemostasis and infected-wound repair in emergency injury events.

Dextran hydrogels via disulfide-containing Schiff base formation: Synthesis, stimuli-sensitive degradation and release behaviors

Dextran hydrogels (Dex-SS) containing both disulfide and Schiff base bonds were developed via facile method based on the dextran oxidation and subsequent formation of Schiff base linkages between polyaldehyde dextran and cystamine, denoted as the disulfide-containing Schiff base reactions. Results of rheology, swelling and 13C CP/MAS NMR study indicated that cross-linking degree of Dex-SS hydrogels depended strongly on the molar ratio of -CHO/-NH2. Acidic and reductive (GSH) environment sensitive degradation behaviors of Dex-SS hydrogels were then evidenced by SEM, rheology study and Ellman’s assay. Moreover, doxorubicin (DOX) was loaded into the hydrogel matrix and pH/GSH-responsive release behaviors were demonstrated. Cytocompatibility of Dex-SS hydrogel and effective cell uptake of released DOX was finally proved by transwell assay with HepG2 cells. Take advantages of the abundance of vicinal hydroxyl on a variety of polysaccharides, the disulfide-containing Schiff base reactions is considered as versatile method to develop stimuli-sensitive hydrogels for local drug delivery.

Dextran-based scaffolds for in-situ hydrogelation: Use for next generation of bioartificial cardiac tissues

In pursuit of a chemically-defined matrix for in vitro cardiac tissue generation, we present dextran (Dex)-derived hydrogels as matrices suitable for bioartificial cardiac tissues (BCT). The dextran hydrogels were generated in situ by using hydrazone formation as the crosslinking reaction. Material properties were flexibly adjusted, by varying the degrees of derivatization and the molecular weight of dextran used. Furthermore, to modulate dextran’s bioactivity, cyclic pentapeptide RGD was coupled to its backbone. BCTs were generated by using a blend of modified dextran and human collagen (hColI) in combination with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and fibroblasts. These hColI + Dex blends with or without RGD supported tissue formation and functional maturation of CMs. Contraction forces (hColI + Dex-RGD: 0.27 ± 0.02 mN; hColI + Dex: 0.26 ± 0.01 mN) and frequencies were comparable to published constructs. Thus, we could demonstrate that, independent of the presence of RGD, our covalently linked dextran hydrogels are a promising matrix for building cardiac grafts.

Antifouling Antioxidant Zwitterionic Dextran Hydrogels as Wound Dressing Materials with Excellent Healing Activities.

Hydrogels as wound dressings have received great attention in recent years. It is highly important yet challenging to develop hydrogel dressings that are biocompatible and that can promote wound healing by lowering the risk of inflammatory responses. In this work, we designed and prepared zwitterionic dextran-based hydrogels using carboxybetaine dextran (CB-Dex) and sulfobetaine dextran (SB-Dex) as raw materials, respectively. The efficacy of CB-Dex and SB-Dex hydrogels in promoting wound recovery was evaluated using a mouse skin wound model. Results suggested that the zwitterionic dextran wound dressings showed a faster healing rate than natural dextran hydrogel and a commercial wound dressing (Duoderm film) due to their excellent protein resistance and capacity to scavenge free hydroxyl radicals. In addition, both CB-Dex and SB-Dex hydrogel wound dressings showed excellent cytocompatibility with NIH3T3 and L929 cells, as well as antibacterial adhesion against Staphylococcus aureus and Escherichia coli. Furthermore, both zwitterionic hydrogels demonstrated self-healing properties and can be stretched to adapt to irregular full-thickness wound beds. More importantly, they can be removed from the wound site painlessly by washing with normal saline. Overall, this work provided a new pathway to fabricate multifunctional polysaccharide hydrogels for wound treatment and pain relief when changing wound dressings.

Adsorption of Sodium Cholate on Cationic Dextran Gels: Comparison of Isotherm Binding Models

Cationic dextran hydrogels having pendent 51-59 mol% N-alkyl-N,N-dimethylammonium chloride groups were synthesized and tested as adsorbents for sodium cholate. The bile acid salt sorption by these gels was evaluated by equilibrium analysis in water and 10 mM NaCl solution. The best adsorption results were obtained with amphiphilic dextran-based gels having two types of pendant ammonium chloride groups with different polarities. Experimental adsorption data for all polymers fitted good with Langmuir, Dubinin-Raduskevich and Temkin models over the entire range of ligand concentrations. The maximum experimental adsorption capacity of dextran sorbents for sodium cholate was in the range 850-1075 mg/g.

Polydopamine Antioxidant Hydrogels for Wound Healing Applications.

Antioxidants are known to improve the wound healing process and are researched as a therapeutic strategy to treat chronic wounds. Dopamine is a known neurotransmitter with antioxidant properties that can be polymerized to form polydopamine (PDA). Herein, polydopamine is demonstrated as an antioxidant biomaterial. In prior work, we developed methodology to prepare hydrogels by crosslinking polysaccharides with polyamines via epichlorohydrin and NaOH. Using this previously developed methodology, dextran hydrogels crosslinked with polydopamine were prepared. Darkening of the gels indicated the increasing incorporation of polydopamine within the hydrogels. In addition to basic pH, polydopamine can be formed by reaction with polyethylene imine (PEI), which results in PEI-PDA copolymer. Dextran was similarly crosslinked with the PEI-PDA copolymer and resulted in sturdier, darker gels, which had more polydopamine incorporated. Hydrogel morphology and strength were dependent on the feed ratios of dopamine. Antioxidant activity of polydopamine containing hydrogel was confirmed and shown to be dependent on the amount of dopamine used in hydrogel synthesis. Hydrogels with 0.5 dopamine to dextran feed ratio scavenged 78.8% of radicals in a 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant assay while gels with no dopamine scavenged only 1.4% of radicals. An ex vivo wound healing assay showed considerable cell migration with the PEI-PDA containing hydrogel.

Polydopamine-incorporated dextran hydrogel drug carrier with tailorable structure for wound healing

Effective methods to treat bacterial infections are highly desired as the abuse of antibiotics has caused multidrug-resistant. Polysaccharide hydrogel-based drug delivery systems possessing inherent large surface area and biocompatibility attributes provide a promising strategy for effective use of antibiotics. Here, we presented an effective method for fabricating macroporous polysaccharide hydrogels composed of dextran (DP) and polydopamine (PDA) for controlled release of antibiotics. The physicochemical properties of resulting DP hydrogels were systematically evaluated by measuring their swelling, viscoelasticity, morphology, sorption and thermal stability, and we could control these properties through simply changing the PDA concentration in a pre-gel solution. The low cytotoxicity of DP hydrogels was demonstrated through a co-culture with mouse fibroblast cells. Moreover, in vitro/vivo antibacterial properties of the drug-loading DP hydrogels were evaluated, and they exhibited good antibacterial and healing performances. We believe that the proposed strategy for facilitation and optimization of polysaccharide hydrogels could offer more hydrogel dressings when choosing suitable carriers for sustained release of antibiotics.

Quantitatively Designed Cross-Linker-Clustered Maleimide–Dextran Hydrogels for Rationally Regulating the Behaviors of Cells in a 3D Matrix

Biomaterials can serve as the cornerstone of extracellular matrices (ECMs) in three-dimensional (3D) cell culture. Designing of diverse ECM materials with adjustable inner structures exhibits growing superiority in inducing varied cellular behaviors, such as spreading, proliferation, migration, differentiation, and apoptosis. However, a rational and easy-to-implement strategy for regulating cell behaviors during cellular self-organization in 3D hydrogels is still lacking. In this study, we propose that maleimide-functionalized dextran hydrogels are cross-linked with quantitatively predesigned nanoscaled heterogeneity. The heterogeneity is obtained via mixing two parts of a dextran polymer with different amounts of available cross-linking sites. We experimentally demonstrate that this rational strategy has a noteworthy impact on cell morphology and fate. The cross-linker-clustered hydrogels are found to contain more microscopic heterogeneous pore structures and show larger heterogeneity in local stiffness, compared to the homogeneously cross-linked hydrogels. Further, 3D cell culture results show that myoblast cells exhibit better spreading, lower circularity, and perceptible changes in the expression of a differentiation marker in cross-linker-clustered hydrogels, which can also be tuned with the cross-linker-clustering degree. The possible mechanisms are discussed by considering the cellular durotaxis in nanoscales, mechanical cues, and biological cues in extracellular and intracellular networks. It is inferred that the effect of nanoscaled durotaxis is triggered during the tentative protrusion of the C2C12 cells, which thus repeatedly and continuously enhances the cellular elongation during their oriented polarization. In conclusion, the predesigned 3D cross-linker-clustered maleimide-dextran hydrogels are able to affect the cell morphology and fate in a rational way by modulating physical, chemical, and biological cues related to the cell-hydrogel interactions. This study provides a promising strategy for quantitative designing and fabrication of functional biomaterials, and theoretical study of mechanobiological mechanisms underlying the cellular behavior.

Conductive poly(2-ethylaniline) dextran-based hydrogels for electrically controlled diclofenac release.

Transdermal drug delivery systems (TDDS) are used as an alternative route to deliver drugs into the blood system for therapy. The matrix materials that have been widely used in TDDS are hydrogels. The dextran hydrogels were prepared by the solution casting using trisodium trimetaphosphate (STMP) as the crosslinking agent, and diclofenac sodium salt (Dcf) as the anionic model drug. Poly(2-ethylaniline) (PEAn) was successfully synthesized and embedded into the dextran hydrogel as the drug encapsulation host. The in-vitro release of Dcf from the hydrogels was investigated using a modified Franz-Diffusion cell in a phosphate-buffered saline (PBS) solution at the pH of 7.4 and at 37°C for a period of 24h, under the effects of crosslinking ratios, dextran molecular weights, electric potentials, and the conductive polymer PEAn. The release mechanism of Dcf from the dextran hydrogels and the composite without electrical potential was the diffusion controlled mechanism or the Fickian diffusion. Under applied electrical potentials, the release mechanism was a combination between the Fickian diffusion and the matrix swelling. The Dcf diffusion coefficients from the dextran hydrogels without electrical potential increased with decreasing crosslinking ratio and molecular weight. Under electrical potentials, the corresponding diffusion coefficients were much higher due mainly to the electro-repulsive force between the negatively charged electrode and the negatively charged dextran and the induced dextran expansion. For the Dcf-loaded PEAn/dextran composite, the diffusion coefficient was enhanced by two orders of magnitude when the electric potential was applied, specifically illustrating the unique features of PEAn as an efficient drug encapsulation host without electric field, and as a drug release enhancer under electric field through the reduction reaction.

Intelligent Drug Delivery Microparticles with Visual Stimuli-Responsive Structural Color Changes.

BackgroundParticle-based drug delivery systems (DDSs) have a demonstrated value for drug discovery and development. However, some problems remain to be solved, such as limited stimuli, visual-monitoring.AimTo develop an intelligent multicolor DDSs with both near-infrared (NIR) controlled release and macroscopic color changes.Materials and MethodsMicroparticles comprising GO/pNIPAM/PEGDA composite hydrogel inverse opal scaffolds, with dextran and calcium alginate hydrogel were synthesized using SCCBs as the template. The morphology of microparticle was observed under scanning electron microscopy, and FITC-dextran-derived green fluorescence images were determined using a confocal laser scanning microscope. During the drug release, FITC-dextran-derived green fluorescence images were captured using fluorescent inverted microscope. The relationship between the power of NIR and the drug release rate was obtained using the change in optical density (OD) values. Finally, the amount of drug released could be estimated quantitatively used the structural color or the reflection peak position.ResultsA fixed concentration 8% (v/v) of PEGDA and 4mg/mL of GO was chosen as the optimal concentration based on the balance between appropriate volume shrinkage and structure color. The FITC-dextran was uniformly encapsulated in the particles by using 0.2 wt% sodium alginate. The microcarriers shrank because of the photothermal response and the intrinsic fluorescence intensity of FITC-dextran in the microparticles gradually decreased at the same time, indicating drug release. With an increasing duration of NIR irradiation, the microparticles gradually shrank, the reflection peak shifted toward blue and the structural color changed from red to orange, yellow, green, cyan, and blue successively. The drug release quantity can be predicted by the structural color of microparticles.ConclusionThe multicolor microparticles have great potential in drug delivery systems because of its vivid reporting color, excellent photothermal effect, and the good stimuli responsivity.