Dextran Methacrylate Research Articles

Self-Extracting Dextran-Based Hydrogel Microneedle Arrays with an Interpenetrating Bioelectroenzymatic Sensor for Transdermal Monitoring with Matrix Protection.

Continuous glucose monitors have revolutionized diabetes management, yet such devices are limited by their cost, invasiveness, and stability. Microneedle (MN) arrays could offer improved comfort compared to invasive implanted or mm-sized needle devices, but such arrays are hampered by complex fabrication processes, limited mechanical and sensor stability, and/or cytotoxicity concerns. This work demonstrates the first crosslinked hydrogel microneedle-bioelectroenzymatic sensor arrays capable of biomarker extraction and robust transdermal continuous monitoring in artificial interstitial fluid for 10 days. The fabrication process via micromolding of dextran-methacrylate (Dex-MA) and dry-state visible light crosslinking is simple and permits the robust fixation of diverse prefabricated electrodes in a single array. Dry-state crosslinking minimized material shrinkage to enable the formation of resistant Dex-MA microneedles with shape control and reproducibility. The polymer substitution level (9-62%) and mass content (10-30wt%) affect the mechanical, swelling, and bioelectrocatalytic properties of the integrated sensors. Crosslinked Dex-MA hydrogel matrices provide beneficial cytotoxicity protection and flux-limiting membrane properties to the integrated second generation dehydrogenase-based nanostructured buckypaper biosensor and Ag/AgCl reference electrodes. Polysaccharide-based microneedle technology with encapsulated porous bioelectrodes promise to be a valuable alternative to more invasive devices for safer and longer-term biomarker monitoring.

Tuning the Porosity of Dextran Microgels with Supramacromolecular Nanogels as Soft Sacrificial Templates.

Hydrogels, as well as colloidal hydrogels (microgels), are important materials for a large variety of applications in the biomedical field. Microgels with a controlled pore size (meso- and macropores) are required for efficient nutrient support, modulation of cell adhesion, removal of metabolic products in cell cultures, and probiotic loading. Common microgel fabrication techniques do not provide sufficient control over pore sizes and geometry. In this work, the natural polysaccharide dextran modified with methacrylate groups is used to synthesize highly monodisperse meso- and macroporous microgels in a size range of100-150µm via photo cross-linking in microfluidic droplets. The size of mesopores is varied by the concentration of dextran methacrylate chains in the droplets (50-200gL-1 ) and the size of macropores is regulated by the integration of pH-degradable supramacromolecular nanogels with diameters of 300 and 700nm as sacrificial templates. Using permeability assays combined with confocal laser scanning microscopy, it is demonstrated that functional dextran-based microgels with uniform and defined pores could be obtained.

A conductive multifunctional hydrogel dressing with the synergistic effect of ROS-scavenging and electroactivity for the treatment and sensing of chronic diabetic wounds

Chronic diabetic wound with persistent inflammatory responses is still a serious threat to human health and life. Ideal wound dressings can be applied not only for covering the injury area, but also for regulating the inflammation to accelerate the wound healing and long-term monitoring of wound condition. However, there remains a challenge to design a multifunctional wound dressing for simultaneous treatment and monitoring of wound. Herein, an ionic conductive hydrogel with intrinsic reactive oxygen species (ROS)-scavenging properties and good electroactivity was developed for achieving the synergetic treatment and monitoring of diabetic wounds. In this study, we modified dextran methacrylate with phenylboronic acid (PBA) to prepare a ROS-scavenging material (DMP). Then the hydrogel was constructed by phenylboronic ester bonds induced dynamic crosslinking network, photo-crosslinked DMP and choline-based ionic liquid as the second network, and the crystallized polyvinyl alcohol as the third network, realizing good ROS-scavenging performance, high electroactivity, durable mechanical properties, and favorable biocompatibility. In vivo results showed that the hydrogel combined with electrical stimulation (ES) demonstrated good performance in promoting re-epithelization, angiogenesis and collagen deposition in chronic diabetic wound treatment by alleviating inflammation. Notably, with desirable mechanical properties and conductivity, the hydrogel could also precisely monitor movements of human body and possible tensile and compressive stresses of the wound site, providing timely alerts of excessive mechanical stress applied to the wound tissue. Thus, this “all-in-one” hydrogel exhibits great potential in constructing the next generation flexible bioelectronics for wound treatment and monitoring. Statement of significanceChronic diabetic wounds characterized by overexpressed reactive oxygen species (ROS) are still a serious threat to human health and life. However, there remains a challenge to design a multifunctional wound dressing for simultaneous wound treatment and monitoring. Herein, a flexible conductive hydrogel dressing with intrinsic ROS-scavenging properties and electroactivity was developed for the combined treatment and monitoring of the wound. The antioxidant hydrogel combined with electrical stimulation synergistically accelerated chronic diabetic wound healing by regulating oxidative stress, alleviating inflammation, promoting re-epithelization, angiogenesis and collagen deposition. Notably, with desirable mechanical properties and conductivity, the hydrogel also presented great potential in monitoring possible stresses of the wound site. The “all-in-one” bioelectronics integrating the treatment and monitoring functions present great application potential for accelerating chronic wound healing.

Dextran Methacrylate Reactions with Hydroxyl Radicals and Hydrated Electrons in Water: A Kinetic Study Using Pulse Radiolysis.

Dextran methacrylate (Dex-MA) is a biodegradable polysaccharide derivative that can be cross-linked by ionizing radiation. It is therefore considered a potential replacement for synthetic hydrophilic polymers in current radiation technologies used for synthesizing hydrophilic cross-linked polymer structures such as hydrogels, mainly for medical applications. This work is focused on the initial steps of radiation-induced cross-linking polymerization of Dex-MA in water. Rate constants of two major transient water radiolysis products-hydroxyl radicals (•OH) and hydrated electrons (eaq-)-with various samples of Dex-MA (based on 6-500 kDa dextrans of molar degree of substitution or DS with methacrylate groups up to 0.66) as well as non-substituted dextran were determined by pulse radiolysis with spectrophotometric detection. It has been demonstrated that these rate constants depend on both the molecular weight and DS; reasons for these effects are discussed and reaction mechanisms are proposed. Selected spectral data of the transient species formed by •OH- and eaq--induced reactions are used to support the discussion. The kinetic data obtained in this work and their interpretation are expected to be useful for controlled synthesis of polysaccharide-based hydrogels and nanogels of predefined structure and properties.

Gelatin-based spongy and compressive resistant cryogels with shape recovery ability as ideal scaffolds to support cell adhesion for tissue regeneration

Methacryloyl gelatin (GelMA) was blended with dextran methacrylate (DexMA) to produce polymer networks with interconnected macropores via cryostructuring and radical crosslinking of the polymers at subzero temperatures. The experimental set-up was optimized to allow the formation of monolithic networks characterized by highly uniform structure with interconnected macropores. The total polymers mass, the amount of the gel-forming reagents and particularly the rheological properties of GelMA resulted the most critical factors for the fabrication of homogeneous and not collapsed scaffolds. Indeed, only the use of GelMA with very low gelation temperature resulted in the formation of uniform monolithic cryogels. However, blending with DexMA produced general worsening of the mechanical properties of the scaffolds, due to DexMA interference with secondary structuring of GelMA during the cryogelation process. DexMA also had negative effect on the ability of the cryogel to support growth and proliferation of HaCat cells, bringing to slower cell adhesion to the scaffold.

Injectable Hydrogel Membrane for Guided Bone Regeneration.

In recent years, multicomponent hydrogels such as interpenetrating polymer networks (IPNs) have emerged as innovative biomaterials due to the synergistic combination of the properties of each network. We hypothesized that an innovative non-animal IPN hydrogel combining self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) with photochemically cross-linkable dextran methacrylate (DexMA) could be a valid alternative to porcine collagen membranes in guided bone regeneration. Calvaria critical-size defects in rabbits were filled with synthetic biphasic calcium phosphate granules in conjunction with Si-HPMC; DexMA; or Si-HPMC/DexMA experimental membranes; and in a control group with a porcine collagen membrane. The synergistic effect obtained by interpenetration of the two polymer networks improved the physicochemical properties, and the gel point under visible light was reached instantaneously. Neutral red staining of murine L929 fibroblasts confirmed the cytocompatibility of the IPN. At 8 weeks, the photo-crosslinked membranes induced a similar degree of mineral deposition in the calvaria defects compared to the positive control, with 30.5 ± 5.2% for the IPN and 34.3 ± 8.2% for the collagen membrane. The barrier effect appeared to be similar in the IPN test group compared with the collagen membrane. In conclusion, this novel, easy-to-handle and apply, photochemically cross-linkable IPN hydrogel is an excellent non-animal alternative to porcine collagen membrane in guided bone regeneration procedures.

Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.

Preparation of new hydrogels by visible light cross-linking of dextran methacrylate and poly(ethylene glycol)-maleic acid copolymer

In this work, a series of new biodegradable and biocompatible hydrogels were synthesized by photopolymerization of dextran-methacrylate (DXM) with poly(ethylene glycol)-maleic acid copolymer (poly(PEG-co-MA, PEGMA)) using (-)-riboflavin as a visible light photoinitiator and L-arginine as a co-photoinitiator. DXM was prepared by acylation of dextran (DX) with methacryloyl chloride (MAC), and PEGMA was synthesized by polycondensation of poly(ethylene glycol) (PEG) and maleic acid (MA). The DXM and PEGMA were characterized by FT-IR and 1HNMR spectroscopy. Different types of hydrogels from various ratios of DXM and PEGMA were prepared and characterized by SEM. The results showed that the prepared hydrogel by photo-cross-linking of DXM (DPHG0) was transparent and flexible, and its physical shape was excellent, but it was sticky. The stickiness was reduced by increasing the PEGMA contents, and different types of DXM/PEGMA hydrogels (DPHG1-4) with various properties were prepared. For example, DPHG2 (PEGMA content was 0.25 g) was transparent and flexible, its physical shape was excellent, and it was not sticky. The prepared hydrogels showed excellent cytocompatibility, and their tensile and compressive strength were also evaluated. Additionally, the in vitro degradation and swelling ratios of the prepared hydrogels were studied in buffer solution at different pHs.

Improved hybrid-shelled perfluorocarbon microdroplets as ultrasound- and laser-activated phase-change platform

HypothesisWe propose significant improvements to perfluorocarbon microdroplets, conferring them colloidal stability, chemical versatility, and size control. Decafluoropentane cores are stabilized by biocompatible interfaces – either a monolayer of the cationic surfactant dimethyldioctadecylammonium bromide (DDAB) or a double shell obtained by adding crosslinked dextran methacrylate as further coating – and functionalised with gold nanoparticles. We hypothesize that this formulation enables dual, acoustic (ADV) and optical (ODV) vaporisation of microdroplets into microbubbles, yielding a versatile “phase-change” theranostic platform. ExperimentsMicrodroplets synthesis is optimized by high-speed homogenization methodology. Functionalisation with gold nanoparticles is achieved by electrostatic decoration. The colloidal suspension is characterised by the concerted use of dynamic light scattering, electrophoresis, and confocal microscopy, to assess microdroplets’ stability. Additional structural details are provided by small-angle X-ray scattering. We analysed the ultrasound- and laser-stimulated transition into microbubbles and characterised their response to ultrasound by acoustic spectroscopy. FindingsHybrid-shelled microdroplets were produced at high density, with narrow diameter distribution (~1 µm). The highly charged surface and the long hydrocarbon tails of DDAB protruding within the core provide high stability. The elastomeric dextran layer at the water interface allows obtaining stable cavitating microbubbles by ADV exhibiting interesting viscoelastic features. The presence of gold nanoparticles unlocks the opto-thermal microdroplet vaporisation.

Dextran-polyethylene glycol cryogels as spongy scaffolds for drug delivery

Cryogels are a particular type of hydrogels that possess great potential in both fields of drug delivery and tissue engineering. Based on these premises, the goal of this work was to develop a cytocompatible polymeric cryogel, which could be used as a spongy scaffold to promote the delivery of biomolecules. Precisely, the novel formulation was fabricated by combining dextran methacrylate (DEX-MA) and polyethylene glycol dimethacrylate (PEG-DMA) through radical polymerization at a temperature of −15 °C. The swelling, porosity, mechanical properties, and the drug release profile of vitamin B12 from the optimized cryogel were evaluated and compared to hydrogels fabricated at room temperature. The use of the cryo-gelation technique enabled the formation of scaffolds with improved swelling, increased interconnected porosity, and higher mechanical resistance than conventional hydrogels. The cryogels proved to be non-toxic and suitable carriers for the delivery of water-soluble biomolecules. Overall, the novel cytocompatible cryogel formulation could be used for biomedical applications that require the need of a macroporous scaffold for localized delivery of bioactive molecules.

Hydroxyapatite-dextran methacrylate core/shell hybrid nanocarriers for combinatorial drug therapy

Abstract

Dextran methacrylate hydrogel microneedles loaded with doxorubicin and trametinib for continuous transdermal administration of melanoma

Microneedles (MNs) technology has many advantages and is an ideal local transdermal drug delivery method. Here we synthesized photocrosslinkable dextran methacrylate (DexMA), and its degree of substitution is 5 % higher than the previous method. We used DexMA hydrogel for the first time to develop a new type of MNs for continuous transdermal administration. The prepared hydrogel MNs can successfully penetrate the epidermal layer and achieve sustained drug release. Doxorubicin (DOX) and trametinib (Tra) are anticancer drugs approved by FDA. Besides, Tra can also reverse P-gp-mediated multidrug resistance (MDR) to effectively block the efflux of DOX by P-gp. We used MNs to simultaneously load Tra and DOX, and achieved synergy in a B16 cell xenograft nude mouse model. The DexMA hydrogel MNs developed in this study can be used to enhance the transdermal delivery of small molecule drugs and reduce systemic toxicity and side effects.

Glycerol as a green solvent for enhancing the formulation of dextran methacrylate and gellan-based semi-interpenetrating polymer networks

Recently, glycerol has been exploited in a number of industrial applications, thanks to its high availability, its low cost and, overall, its peculiar properties which fit well with the green chemistry principles. In this work, the ability of glycerol to solubilize high molecular weight polymers and to allow the formation of glycerol-based semi-interpenetrating polymer networks, called “gly-semi-IPNs”, has been investigated. Compared to water, glycerol deeply affects the structural properties of the biopolymers, especially with reference to their chain flexibility. Among the polysaccharides, dextran methacrylate (DexMA) and gellan gum (Ge) were selected. Glycerol solutions of both polysaccharides and their mixtures, as well as a DexMA network (obtained by cross-linking in glycerol and in the presence of a photoinitiator), were rheologically characterized to assess the role of the solvent on the chain conformation and on the mechanical properties of the networks. Interestingly, glycerol was found to deeply influence the mechanical, morphological and optical properties of the formed hydrogels, as well as to improve the cross-linking kinetic of DexMA. Furthermore, glycerol leads to more homogeneous mixtures of the two polysaccharides than those observed in aqueous buffers. As such, novel gly-semi-IPNs, with enhanced formulation and mechanical properties, were prepared and characterized.

Photoclick chemistry to create dextran-based nucleic acid microarrays.

In the literature, there are reports of the utilization of various hydrogels to create generic platforms for protein microarray applications. Here, a novel strategy was developed to obtain high-performance microarrays. In it, a dextran hydrogel is used to covalently immobilize oligonucleotides and proteins. This method employs aqueous solutions of dextran methacrylate (Dx-MA), which is a biocompatible photopolymerizable monomer. Capture probes are immobilized inside the hydrogel via a light-induced thiol-acrylate coupling reaction at the same time as the dextran polymer is formed. Hydrogel microarrays based on this technique were prepared on different surfaces, such as a Blu-ray Disk and polycarbonate or alkene-functionalized glass slides, and these systems showed high probe-loading capabilities and good biorecognition yields. This methodology presents advantages such as a low cost, a short analysis time, a low limit of detection, and multiplexing capabilities, among others. Confocal fluorescence microscopy analysis demonstrated that in these hydrogel-based microarrays, receptor immobilization and the biorecognition event occurred within the hydrogel and not merely on the surface.

Cell force-mediated matrix reorganization underlies multicellular network assembly

Vasculogenesis is the de novo formation of a vascular network from individual endothelial progenitor cells occurring during embryonic development, organogenesis, and adult neovascularization. Vasculogenesis can be mimicked and studied in vitro using network formation assays, in which endothelial cells (ECs) spontaneously form capillary-like structures when seeded in the appropriate microenvironment. While the biochemical regulators of network formation have been well studied using these assays, the role of mechanical and topographical properties of the extracellular matrix (ECM) is less understood. Here, we utilized both natural and synthetic fibrous materials to better understand how physical attributes of the ECM influence the assembly of EC networks. Our results reveal that active cell-mediated matrix recruitment through actomyosin force generation occurs concurrently with network formation on Matrigel, a reconstituted basement membrane matrix regularly used to promote EC networks, and on synthetic matrices composed of electrospun dextran methacrylate (DexMA) fibers. Furthermore, modulating physical attributes of DexMA matrices that impair matrix recruitment consequently inhibited the formation of cellular networks. These results suggest an iterative process in which dynamic cell-induced changes to the physical microenvironment reciprocally modulate cell behavior to guide the formation and stabilization of multicellular networks.

Direct Synthesis of Dextran-Based Antibacterial Hydrogels for Extended Release of Biocides and Eradication of Topical Biofilms.

Cationic small molecular biocides have been developed as promising antibiofilm agents because of their tunability in chemical structures and their ability to disrupt established biofilms. However, the impact of biocides in antibiofilm treatment is largely limited due to the lack of an effective delivery system that can ensure sustained release of biocides at the target site. Herein we report a biocide-encapsulated antibacterial and antibiofilm hydrogel that acts as an efficient delivery vehicle for the biocide and eradicates matured bacterial biofilm. The hydrogels are prepared using dextran methacrylate (Dex-MA), a biocompatible and photopolymerizable polymer, and a nontoxic cationic biocide with two cationic charges, two nonpeptidic amide bonds, and optimized amphiphilicity, which is capable of eradicating established bacterial biofilms. The gels, prepared via direct loading of the biocide and with highly controllable amounts, display 100% activity against both drug-sensitive and drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Importantly, the gels are shown to release the biocide and kill bacteria for an extended period of time (until day 5). When being treated with the established bacterial biofilms, the released biocide from the gel is shown to completely eradicate establishedS. aureus, Escherichia coli, and MRSA biofilms, the most common biofilm forming bacteria that cause severe infections (e.g., skin infections, urinary tract infections, etc.) in humans. Moreover, the gels were shown to annihilate preformed MRSA biofilm with >99.99% bacterial reduction under in vitro and in vivo conditions in a superficial MRSA infection model in mice. Notably, when tested, excellent skin compatibility is observed for these materials in various animal models such as a rat model of acute dermal toxicity, guinea pig model of skin sensitization, and rabbit model of skin irritation. The biocompatible antibacterial and antibiofilm hydrogels developed herein thus might be useful in treating bacterial biofilm associated infections, especially topical infections.

Radiation synthesis of biocompatible hydrogels of dextran methacrylate

The aim of this work was to synthesize biocompatible dextran-based hydrogels through crosslinking initiated by ionizing radiation. A series of derivatives of dextran has been synthesized by coupling of methacrylated glycidyl to the structure of this polysaccharide, yielding dextran methacrylate (Dex-MA) of the degree of methacrylate substitution (DS) up to 1.13 as characterised by FTIR and NMR spectroscopy. Chemically crosslinked hydrogels were formed by electron-beam irradiation of Dex-MA in aqueous solution in the absence of low-molecular-weight additives such as catalysts, monomers or crosslinking agents. Crosslinking of Dex-MA in aqueous solutions of 20g/l and above was an efficient process, the gels were formed at doses as low as 0.5 kGy (experiments conducted up to 100 kGy) and were characterised by high content of insoluble fraction (70–100%). Due to high crosslinking density the equilibrium degree of swelling of fabricated gels was controlled principally by the initial concentration of Dex-MA solution subjected to irradiation, and it was in the range of 20 to over 100g of water absorbed by gram of gel. Cytocompatibility of hydrogels was examined using XTT assay through evaluation of the cell viability being in indirect contact with hydrogels. The results indicated that hydrogels of Dex-MA of the average DS below 1 were not cytotoxic. Altogether, our data demonstrate that irradiation of methacrylated dextran in aqueous solution is an efficient method of fabrication of biocompatible hydrogels, which applications in regeneration medicine are anticipated.

New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization

A new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX–PEG–MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX–PEG–MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX–MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX–MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affect the release of a model macromolecule over time, making DEX–PEG–MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules.

Superhydrophobic Surfaces as a Tool for the Fabrication of Hierarchical Spherical Polymeric Carriers.

Hierarchical polymeric carriers with high encapsulation efficiencies are fabricated via a biocompatible strategy developed using superhydrophobic (SH) surfaces. The carries are obtained by the incorporation of cell/BSA-loaded dextran-methacrylate (DEXT-MA) microparticles into alginate (ALG) macroscopic beads. Engineered devices like these are expected to boost the development of innovative and customizable systems for biomedical and biotechnological purposes.

Highly ordered and tunable polyHIPEs by using microfluidics.

We demonstrate how to generate highly ordered porous matrices from dextran-methacrylate (DEX-MA) using microfluidics. We use a flow focusing device to inject an aqueous solution of DEX-MA and surfactant to break the flow of an organic solvent (cyclohexane) into monodisperse droplets at a high volume fraction (above 74% v/v) to form an ordered high internal phase emulsion (HIPE). We collect the crystalline HIPE structure and freeze it by gelling. The resulting polyHIPEs are characterized by an interconnected and ordered morphology. The size of pores and interconnects ranges between hundreds and tens of micrometers, respectively. The technique that we describe allows for precise tuning of all the structural parameters of the matrices, including their porosity, the size of the pores and the lumen of interconnects between the pores. The resulting ordered and precisely tailored HIPE gels represent a new class of scaffolds for applications in tissue engineering.