Dextran Hydrogels Research Articles

A carboxymethyl chitosan and dextran hydrogel with slow and rapid photothermal conversion for sequential promoting burn wound healing and inhibiting scar proliferation

Facilitating swift burn wound healing while effectively preventing scar formation continues to be a considerable challenge in medical practice. In this study, an injectable carboxymethyl chitosan/oxidized dextran/polyvinylpyrrolidone/dopamine (COPD) hydrogel was designed for the effective sequentially promotion of burn wound healing and inhibition of scar formation. The COPD hydrogel precursor solution was injected into the burn wound via a double-barreled syringe and transformed into an adherent hydrogel within 25 s. The inclusion of dopamine imparted good free radical scavenging properties to the hydrogel. In particular, the gradual oxidation of dopamine to polydopamine enabled a unique heat production pattern—initially slow (photothermal conversion efficiency: 30.3 %) and then rapidly temperature increasing (photothermal conversion efficiency: 42.8 %) —under single laser irradiation. The effect of promoting healing at the initial stage of the wound was evaluated by constructing a male C57BL/6 mice model with deep second-degree burns, observation of the wound area, PCR analysis, and immunohistochemical staining. Furthermore, the scar inhibition was confirmed by observing reduced expression levels of α-SMA and COLI, along with a decreased collagen I/III ratio. With tunable mechanical properties (maximum compressive strength of 966.4 ± 51.7 kPa), the COPD hydrogel holds significant promise as an adjunctive photothermal platform for intelligent burn wound management.

RGD peptide promotes follicle growth through integrins αvβ3/αvβ5 in three-dimensional culture.

Three-dimensional ovarian tissue culture is a unique model to define the effects of molecules on folliculogenesis. Using this model, we determined that RGD-integrin interaction plays a role in antrum formation and theca cell differentiation. We recently developed a three-dimensional (3D) ovarian tissue culture system supported by bacterial-derived dextran hydrogel. Arg-Gly-Asp (RGD) is an extracellular matrix-derived triple peptide. Immature ovarian tissues cultured in RGD-modified dextran hydrogel significantly promoted antral follicle growth and oocyte quality compared with those cultured in dextran hydrogel alone. In this study, we examined the mechanism of follicle growth stimulated by RGD treatment in the 3D system. First, we detected that direct contact between RGD-modified dextran hydrogel and ovarian interstitial cells is necessary to promote antral follicle growth. Therefore, we hypothesized that RGD stimulates antral follicle growth through RGD-binding integrin receptors expressed in the interstitial cell mass. Using quantitative PCR (qPCR) and immunochemical staining, we identified that integrins ⍺vβ3 and ⍺v5 are predominantly expressed in the ovarian interstitial compartment. To assess the effect of RGD-integrin interaction on follicle growth, ovarian tissues were cultured with cilengitide (Ci), an inhibitor specific for ⍺vβ3 and ⍺vβ5. Ci treatment suppressed RGD-induced follicle growth and oocyte quality in a dose-dependent manner. When the interstitial cell aggregates were cultured with RGD, cell migration and theca-related gene expression were significantly upregulated. Ci treatment dramatically suppressed these RGD-induced activities. In coculturing the interstitial aggregate and secondary follicles with RGD, migrating cells formed the outermost cell layers around the follicles, like theca layers, which were totally blocked by Ci treatment. In conclusion, our results suggest that RGD stimulates theca cell differentiation in the ovarian interstitial cells through integrins ⍺vβ3 and ⍺v5 to promote antral follicle growth in our 3D system.

Water-based synthesis of dextran-methacrylate and its use to design hydrogels for biomedical applications

Polysaccharide-based hydrogels are desirable for biomedical applications owing to their biocompatibility and physicochemical tunability. The chemical modification of polysaccharides with photo-sensitive groups, such as methacrylates is a common method to obtain new hydrogel materials. This study introduces a non-toxic water-based method to effectively functionalize dextran with methacrylate groups. The methacrylation reaction with methacrylic anhydride in water in the presence of NaOH was rapid and efficient (85 %−92 % yield), permitting degrees of substitution (DS) up to 62 % within 60 min. An unconventional solid-state photo-crosslinking method was employed to form chemically crosslinked dextran-based hydrogels with LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as the photoinitiator. By varying the polymer formulations (DS, polymer mass, LAP concentration), a wide range of hydrogels were obtained with various swelling ratios (40–250 %) and release kinetics of model drug and protein biomolecules. Compression modulus values ranged from 32 ± 1 to 342 ± 10 MPa (dry state) and 87 to 8500 kPa (swollen state). Cytotoxicity experiments indicated good biocompatibility for the crosslinked dextran hydrogels. The green synthesis protocols and obtained dextran-based hydrogels with high mechanical strength open up perspectives for applications from tissue engineering to the design of medical devices such as microneedles.

Stabilization of Picea abies Spruce Bark Extracts within Ice-Templated Porous Dextran Hydrogels.

Porous hydrogels have brought more advantages than conventional hydrogels when used as chromatographic materials, controlled release vehicles for drugs and proteins, matrices for immobilization or separation of molecules and cells, or as scaffolds in tissue engineering. Polysaccharide-based porous hydrogels, in particular, can address challenges related to bioavailability, solubility, stability, and targeted delivery of natural antioxidant compounds. Their porous structure enables the facile encapsulation and controlled release of these compounds, enhancing their therapeutic effectiveness. In this context, in the present study, the cryogelation technique has been adopted to prepare novel dextran (Dx)-based porous hydrogels embedding polyphenol-rich natural extract from Picea abies spruce bark (SBE). The entrapment of the SBE within the Dx network was proved by FTIR, SEM, and energy-dispersive X-ray spectroscopy (EDX). SEM analysis showed that entrapment of SBE resulted in denser cryogels with smaller and more uniform pores. Swelling kinetics confirmed that higher concentrations of Dx, EGDGE, and SBE reduced water uptake. The release studies demonstrated the effective stabilization of SBE in the Dx-based cryogels, with minimal release irrespective of the approach selected for SBE incorporation, i.e., during synthesis (~3-4%) or post-synthesis (~15-16%). In addition, the encapsulation of SBE within the Dx network endowed the hydrogels with remarkable antioxidant and antimicrobial properties. These porous biomaterials could have broad applications in areas such as biomedical engineering, food preservation, and environmental protection, where stability, efficacy, and safety are paramount.

Cofunctionalization of Macroporous Dextran Hydrogels with Adhesive Peptides and Growth Factors Enables Vascular Spheroid Sprouting.

Ensuring good definition of scaffolds used for 3D cell culture is a prominent challenge that hampers the development of tissue engineering platforms. Since dextran repels cell adhesion, using dextran-based materials biofunctionalized through a bottom-up approach allows for precise control over material definition. Here, we report the design of dextran hydrogels displaying a fully interconnected macropore network for the culture of vascular spheroids in vitro. We biofunctionalized the hydrogels with the RGD peptide sequence to promote cell adhesion. We used an affinity peptide pair, the E/K coiled coil, to load the gels with epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Dual functionalization with adhesive and proliferative cues allows vascular spheroids to colonize naturally cell-repellant dextran. In supplement-depleted medium, we report improved colonization of the macropores compared to that of unmodified dextran. Altogether, we propose a well-defined and highly versatile platform for tissue engineering and tissue vascularization applications.

A Microenvironment-Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti-Infection and Osteo-Immune Modulation.

Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant-derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan-Oxidized Dextran (CMCS-OD) hydrogel formed via dynamic chemical bonds exhibited self-healing capabilities and pH-responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis-induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis-induced bone destruction.

Rational Design of Liquid-Liquid Microdispersion Droplet Microreactors for the Controllable Synthesis of Highly Uniform and Monodispersed Dextran Microspheres.

Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 μm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.

Copper peroxide loaded gelatin/oxide dextran hydrogel with temperature and pH responsiveness for antibacterial and wound healing activity

Bacterial infection and tissue hypoxia always prevent wound healing, so multifunctional platforms with antimicrobial and oxygen-supplying functions were developed. However, they face many difficulties such as complex preparation and low oxygen release. To address this challenge, a copper peroxide loaded gelatin/oxide dextran hydrogel (CGO) was prepared. Surprisingly, CGO hydrogel as a wound dressing not only had good biocompatibility, injectivity, and mechanical properties, but also exhibited mild photothermal properties, temperature responsiveness, and pH responsiveness. After being applied to wounds infected with bacteria, CGO hydrogel released copper peroxide under near-infrared laser irradiation, which produced copper ions and hydrogen peroxide, combined with PTT to kill bacteria. After the bacteria were cleared from the wound and the pH of the wound was changed to be acidic, CGO hydrogel released copper peroxide via pH response. Copper ions and oxygen produced from copper peroxide accelerated wound healing by promoting angiogenesis. The multi-responsive and multi-mode treatment platform provided a potential strategy for treating bacteria-infected wounds.

The Diels-Alder Cross-Linked Gelatin/Dextran Nanocomposite Hydrogels with Silver Nanoparticles for Wound Healing Applications: Synthesis, Characterization, and In Vitro Evaluation.

Wound healing involves a sophisticated biological process that relies on ideal conditions to advance through various stages of repair. Modern wound dressings are designed to imitate the natural surroundings around cells and offer properties such as moisture regulation, strength, and antimicrobial defense to boost healing. A recent research project unveiled a new type of gelatin (Gel)/dextran (Dex) hydrogels, linked through Diels-Alder (D-A) reactions, loaded with silver nanoparticles (Ag-NPs) for cutting-edge wound treatment. Gel and Dex were chemically modified to form the hydrogels via the D-A reaction. The hydrogels were enriched with Ag-NPs at varying levels. Thorough analyses of the hydrogels using methods like NMR, FT-IR, and SEM were carried out to assess their structure and nanoparticle integration. Rheological tests displayed that the hydrogels had favorable mechanical attributes, particularly when Ag-NPs were included. The hydrogels demonstrated controlled swelling, responsiveness to pH changes, and were non-toxic. Testing against E. coli showcased the strong antibacterial activity of the nanocomposite hydrogels in a concentration-dependent manner. This investigation showcased the promise of these bioactive nanocomposite hydrogels in promoting speedy wound healing by maintaining a moist environment, offering an antimicrobial shield, and ensuring mechanical support at the wound site.

Oral biomimetic virus vaccine hydrogel for robust abscopal antitumour efficacy

Remarkable progress has been made in tumour immunotherapy in recent decades. However, the clinical outcomes of therapeutic interventions remain unpredictable, largely because of inefficient immune responses. To address this challenge and optimise immune stimulation, we present a novel administration route for enhancing the bioavailability of immunotherapeutic drugs. Our approach involves the development of an oral tumour vaccine utilising virus-like particles derived from the Hepatitis B virus core (HBc) antigen. The external surfaces of these particles are engineered to display the model tumour antigen OVA, whereas the interiors are loaded with cytosine phosphoguanosine oligodeoxynucleotide (CpG ODN), resulting in a construct called CpG@OVAHBc with enhanced antigenicity and immune response. For oral delivery, CpG@OVAHBc is encapsulated in a crosslinked dextran hydrogel called CpG@OVAHBc@Dex. The external hydrogel shield safeguards the biomimetic virus particles from degradation by gastric acid and proteases. Upon exposure to intestinal flora, the hydrogel disintegrates, releasing CpG@OVAHBc at the intestinal mucosal site. Owing to its virus-like structure, CpG@OVAHBc exhibits enhanced adhesion to the mucosal surface, facilitating uptake by microfold cells (M cells) and subsequent transmission to antigen-presenting cells. The enzyme-triggered release of this oral hydrogel ensures the integrity of the tumour vaccine within the digestive tract, allowing targeted release and significantly improving bioavailability. Beyond its efficacy, this oral hydrogel vaccine streamlines drug administration, alleviates patient discomfort, and enhances treatment compliance without the need for specialised injection methods. Consequently, our approach expands the horizons of vaccine development in the field of oral drug administration.

Nitric oxide-releasing multifunctional catechol-modified chitosan/oxidized dextran hydrogel with antibacterial, antioxidant, and pro-angiogenic properties for MRSA-infected diabetic wound healing

The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves ∼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, •OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.

Cowberry extract loaded chitosan hydrogel with photothermal and antioxidant properties promotes infected wound healing

Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.

Application of photocrosslinked gelatin, alginate and dextran hydrogels in the in vitro culture of testicular tissue

Testicular tissue culture in vitro is considered an important tool for the study of spermatogenesis and the treatment of male infertility. Although agarose hydrogel is commonly used in testicular tissue culture, the efficiency of spermatogenesis in vitro is limited. In this study, testicular tissues from adult mice were cultured using a gas-liquid interphase method based on agarose (Agarose), gelatin methacryloyl (GelMA), alginate methacryloyl (AlgMA), dextran methacryloyl (DexMA), and mixture GelMA-Agarose, AlgMA-Agarose, and DexMA-Agarose hydrogels, respectively, for 32 days in vitro. The integrity of the seminiferous tubules, the density and proportions of spermatogonia, spermatocytes, Sertoli cells, and testosterone concentrations were quantified and compared between groups. Properties of different hydrogels including compression modulus, Fourier Infrared Spectroscopy (FITR) spectra, pore size, water absorption, and water retention were tested to investigate how biochemical and physical properties of hydrogels affect the results of testicular tissue culture. The results indicate that testicular tissues cultured on AlgMA exhibited the highest seminiferous tubule integrity rate (0.835 ± 0.021), the presence of a high density of spermatocytes (2107.627 ± 232.082/mm2), and a high proportion of SOX9-positive well-preserved seminiferous tubules (0.473 ± 0.047) compared to all remaining experimental groups on day 32. This may be due to the high water content of AlgMA reducing the toxic effect of oxygen on testicular tissue. In the later period of culture, testicular tissues cultured on DexMA, not DexMA-Agarose, produced significantly more testosterone (18.093 ± 3.302 ng/mL) than the other groups, suggesting that DexMA is friendly to Leydig cells. Our study provides a new idea for the optimization of the gas-liquid interphase method for achieving in vitro spermatogenesis, facilitating the future achievement of efficient in vitro spermatogenesis in more species, including humans.

Structuring gelatin methacryloyl - dextran hydrogels and microgels under shear.

Gelatin methacryloyl (GelMA) is a widely used semi-synthetic polymer for a variety of bioapplications. However, the development of versatile GelMA hydrogels requires tuning of their microstructure. Herein, we report the possibility of preparing hydrogels with various microstructures under shear from an aqueous two-phase system (ATPS) consisting of GelMA and dextran. The influence of an applied preshear on dextran/GelMA droplets and bicontinuous systems is investigated by rheology that allows the application of a constant shear and is immediately followed by in situ UV-curing of the GelMA-rich phase. The microstructure of the resulting hydrogels is examined by confocal laser scanning microscopy (CLSM). The results show that the GelMA string phase and GelMA hydrogels with aligned bands can be formed depending on the concentration of dextran and the applied preshear. The influence of the pH of the ATPS is investigated and demonstrates the formation of multiple emulsions upon decreasing the charge density of GelMA. The preshearing of multiple emulsions, following gelation, leads to the formation of porous GelMA microgels. The diversity of the formed structures highlights the application potential of preshearing ATPS in the development of functional soft materials.

Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects.

During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix. In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments. The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01). In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.

Water Dynamics in Dextran-Based Hydrogel Micro/Nanoparticles Studied by NMR Diffusometry and Relaxometry.

Water dynamics in mesoporous dextran hydrogel micro/nanoparticles was investigated by means of nuclear magnetic resonance (NMR) techniques. High-resolution 1H NMR spectra and pulsed field gradient (PFG) NMR diffusometry measurements obtained on swollen state dextran micro/nanogel revealed the existence of different fractions of water molecules based on their interaction with the gel matrix. In addition to the translational diffusion of bulk water, two more diffusion processes characterized with self-diffusion coefficients 1 and 2 orders of magnitude smaller than that of bulk water were identified. 1H spin-lattice relaxation dispersion profiles obtained for a broad range of Larmor frequencies using fast field cycling (FFC) and conventional NMR relaxometry techniques allowed us to further clarify the mechanisms of molecular motion. According to the water proton pool fractions and associated self-diffusion coefficients, it is shown that the relaxation contribution associated with reorientation-mediated translational motions (RMTDs) dominates the relaxation dispersion observed at intermediate frequencies. At very low frequencies, the spin-lattice relaxation rate is dominated by the slow solid-gel dynamics probed by the water molecules interacting with the pores' surface hydroxyl groups due to the rapid chemical exchange between surface hydroxyl groups and free water. The correlation time for the thumbling-like motion of the dextran gel was found to be in the submillisecond range. The values of the self-diffusion and coherence lengths associated with motion of water molecules interacting with the solid-gel particles are consistent with the particle size and pore size distributions obtained for the studied dextran gels.

Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Chitosan and dextran hydrogel as a filler for possible application in orthopedic implantation surgery

To enhance osteointegration between bone implants and bone tissues in implantation surgery, this study aimed to develop a hydrogel using chitosan and dextran to improve the cell proliferative ability, cell migratory capacity, and cell osteogenic ability. Herein, we developed two different hydrogel compositions with three different amounts of magnesium sulfate to produce six hydrogels for application as a filler for total knee replacement surgery to replace bone cement. The swelling property, degradation behavior, composition, and structure of the hydrogel were systemically investigated. Moreover, an MTT assay, scratch test, and alizarin red S staining were conducted to analyze the cell viability, migratory ability, and osteogenic response after being stimulated by the hydrogel. MC3T3-E1 preosteoblasts exhibited significantly improved cell proliferation, migratory capacity, osteogenesis, and mineralization due to MgSO4 in the hydrogel. Our work provides insights into the development of biomimetic and osteogenic hydrogels for bone integration in implantation surgery.

Matrix stiffness regulates neovascular homeostasis through autophagy in nude mice.

One of the major obstacles to the effective application of vascularized fruit is an insufficient understanding of the relationship between the microenvironment and neovascular homeostasis. The role of extracellular matrixstiffness in regulating the structural and functional stability of neovascularization has not yet been elucidated. This study explored the effects of matrix stiffness on neovascular homeostasis in nude mice. Dextran hydrogels with three different stiffnesses were separately combined with mouse bone marrow-derived endothelial progenitor cells (EPCs) and subcutaneously implanted into the backs of nude mice. After 14 days, neovascular homeostasis indicators in the different groups were measured. Cell autophagy levels were evaluated, and inhibitor assays were performed to explore the underlying mechanism. New blood vessels were generated in the three stiffnesses of the EPC-loaded dextran hydrogels 14 days after implantation. The newly formed vessels tended to have better structural stability in softer hydrogels. Endothelial function markers, such as endothelial nitric oxide synthaseand E-selectin, were downregulated as the matrix stiffness increased. Furthermore, we found that cell autophagy levels decreased in stiffer matrices, and autophagy inhibition attenuated neovascular homeostasis. A soft matrix is conducive to maintaining neovascular homeostasis through autophagy in nude mice.

Injectable multifunctional chitosan/dextran-based hydrogel accelerates wound healing in combined radiation and burn injury

Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H2O2-induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI.