Hierarchical Porous Aerogels With Multiple Adsorptive Interactions for Dye Wastewater Purification.

Aerogels present a huge potential for removing organic dyes from printing and dyeing wastewater (PDW). However, the preparation of aerogels with multiple dye adsorption capabilities remains a challenge, as many existing aerogels are limited to adsorbing only a single type of dye. Herein, a composite aerogel (CG/T-rGO) with the addition of carboxymethyl chitosan, gelatin and tannic acid reduced graphene oxide (T-rGO) was synthesized by freeze-drying technology. The electrostatic interactions between dye molecular and GEL/CMCS (CG) networks, as well as the supramolecular interactions (H-bonds, electrostatic interactions and π-π stacks) between T-rGO, have endowed the aerogel with the ability to adsorb multiple types of dye, such as methylene blue (MB) and methyl orange (MO). Results exhibited that the prepared CG/T-rGO aerogel possessed strong mechanical strength and a porous 3D network structure with a porosity of 96.33 %. Using MB and MO as adsorbates, the adsorption capacity (88.2 mg/g and 66.6 mg/g, respectively) and the mechanism of the CG/T-rGO aerogel were investigated. The adsorption processes of aerogel for MB and MO were shown to follow the pseudo-second-order kinetic model and Langmuir isotherm model, indicating the chemical adsorption of a monolayer. The proposed aerogel in this work has promising prospects for dye removal from PDW.

Oral Delivery of Astaxanthin via Carboxymethyl Chitosan-Modified Nanoparticles for Ulcerative Colitis Treatment.

The oral delivery strategy of natural anti-oxidant and anti-inflammatory agents has attracted great attention to improve the effectiveness of ulcerative colitis (UC) treatment. Herein, we developed a novel orally deliverable nanoparticle, carboxymethyl chitosan (CMC)-modified astaxanthin (AXT)-loaded nanoparticles (CMC-AXT-NPs), for UC treatment. The CMC-AXT-NPs were evaluated by appearance, morphology, particle size, ζ-potential, and encapsulation efficiency (EE). The results showed that CMC-AXT-NPs were nearly spherical in shape with a particle size of 34.5 nm and ζ-potential of -30.8 mV, and the EE of CMC-AXT-NPs was as high as 95.03%. The CMC-AXT-NPs exhibited preferable storage stability over time and well-controlled drug-release properties in simulated intestinal fluid. Additionally, in vitro studies revealed that CMC-AXT-NPs remarkably inhibited cytotoxicity induced by LPS and demonstrated superior antioxidant and anti-inflammatory abilities in Raw264.7 cells. Furthermore, CMC-AXT-NPs effectively alleviated clinical symptoms of colitis induced by dextran sulfate sodium salt (DSS), including maintaining body weight, inhibiting colon shortening, and reducing fecal bleeding. Importantly, CMC-AXT-NPs suppressed the expression of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1ß and ameliorated DSS-induced oxidative damage. Our results demonstrated the potential of CMC-modified nanoparticles as an oral delivery system and suggested these novel AXT nanoparticles could be a promising strategy for UC treatment.

Effect of chitosan and CMCS on dentin after Er:YAG laser irradiation: shear bond strength and surface morphology analysis.

OBJECTIVES: The aim of the present study was to evaluate the effect of chitosan and carboxymethyl chitosan (CMCS) on dentin surface morphology and bonding strength after irradiation of Er:YAG laser. METHODS: Eighty-four laser-irradiated dentin samples were randomly distributed into three groups (n = 28/group) according to different surface conditioning process: deionized water for 60s; 1wt% chitosan for 60s; or 1wt% CMCS for 60s. Two specimens from each group were subjected to TEM analysis to confirm the presence of extrafibrillar demineralization on dentin fibrils. Two specimens from each group were subjected to morphological analysis by SEM. Seventy-two specimens (n = 24/group) were prepared, with a composite resin cone adhered to the dentin surface, and were then randomly assigned to one of two aging processes: storage in deionized water for 24 h or a thermocycling stimulation. The shear bond strength of laser-irradiated dentin to the resin composite was determined by a universal testing machine. Data acquired in the shear bond strength test was analyzed by one-way ANOVA with the Tukey honestly significant difference post hoc test and Independent Samples t-test (α = 0.05). RESULTS: CMCS group presented demineralized zone and a relatively smooth dentin surface morphology. CMCS group had significantly higher SBS value (6.08 ± 2.12) without aging (p < 0.05). After thermal cycling, both chitosan (5.26 ± 2.30) and CMCS group (5.82 ± 1.90) presented higher bonding strength compared to control group (3.19 ± 1.32) (p < 0.05). Chitosan and CMCS group preserved the bonding strength after aging process (p > 0.05). CONCLUSIONS: CMCS has the potential to be applied in conjunction with Er:YAG laser in cavity preparation and resin restoration.

Assessment of the ability of Pseudomonas aeruginosa and Staphylococcus aureus to create biofilms during wound healing in a rat model treated with carboxymethyl cellulose/carboxymethyl chitosan hydrogel containing EDTA.

The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic acid (EDTA) as the materials for wound healing. CMC and CMCS solutions were prepared with a concentration of 4% (w/v). These solutions were made using normal saline serum with a concentration of 0.5% (v/v). Additionally, EDTA with the concentrations of 0.01%, 0.05%, 0.1%, 0.5%, 1%, and 2% (w/v) was included in the prepared polymer solution. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with average in size 88.71 ± 5.93 µm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. The antibacterial experiments showed that the formulated CMC/CMCS/EDTA 0.5% hydrogel inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, the produced hydrogels were haemocompatible and biocompatible. At the last stage, the evaluation of wound healing in the animal model demonstrated that the use of the produced hydrogels significantly improved the process of wound healing. Finally, the findings substantiated the effectiveness of the formulated hydrogels as the materials for promoting wound healing and antibacterial agents.

Strong infiltrative HHC36 antimicrobial peptide/silver nanoparticles-loaded carboxymethyl chitosan/sodium alginate hydrogel for acne vulgaris therapy.

Acne is a common chronic skin inflammatory disease closely related toCutibacterium acnes(C. acnes), which affects the life quality of patients worldwide, especially adolescents and young adults. However, the physical barrier of the skin makes drugs difficult to infiltrate effectively into infected site, causing acne hard to cure and easy to recur. Herein, we developed an antibacterial skin dressing with strong infiltration of antibacterial agents which can co-delivery small-molecular antimicrobial agents through stratum corneum deeply into dermis, achieving high antimicrobial efficacy. The antibacterial dressings were constructed with carboxymethyl chitosan/sodium alginate (CMCS/SA) hydrogel loading with HHC36 (an antimicrobial peptide) and silver nanoparticles (AgNPs) conjugates (Ag-H2/CMCS/SA hydrogel). The released Ag-H2from Ag-H2/CMCS/SA hydrogel can early infiltrate into dermis, co-delivery HHC36 and AgNPs due to the infiltration and targeting of HHC36, presenting the superior antibacterial effect compared to HHC36 or AgNPs alone and killing 100%C. acnesand 100%Staphylococcus epidermidis(S. epidermidis) at a very low concentration of Ag-H2(15µg ml-1A g with 7.1µg ml-1HHC36). Meanwhile, Ag-H2/CMCS/SA hydrogel was biocompatible due to the natural polysaccharides carboxymethyl chitosan and sodium alginate. The HaCaT cells spread well in Ag-H2/CMCS/SA hydrogel. These results indicate that the co-delivery small-molecular antimicrobial agents is a promising strategy and Ag-H2/CMCS/SA hydrogel has a great potential in the therapy of acne.

Preparation and Antioxidant Activity of New Carboxymethyl Chitosan Derivatives Bearing Quinoline Groups.

A total of 16 novel carboxymethyl chitosan derivatives bearing quinoline groups in four classes were prepared by different synthetic methods. Their chemical structures were confirmed by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and elemental analysis. The antioxidant experiment results in vitro (including DPPH radical scavenging ability, superoxide anion radical scavenging ability, hydroxyl radical scavenging ability, and ferric reducing antioxidant power) demonstrated that adding quinoline groups to chitosan (CS) and carboxymethyl chitosan (CMCS) enhanced the radical scavenging ability of CS and CMCS. Among them, both N, O-CMCS derivatives and N-TM-O-CMCS derivatives showed DPPH radical scavenging over 70%. In addition, their scavenging of superoxide anion radicals reached more than 90% at the maximum tested concentration of 1.6 mg/mL. Moreover, the cytotoxicity assay was carried out on L929 cells by the MTT method, and the results indicated that all derivatives showed no cytotoxicity (cell viability > 75%) except O-CMCS derivative 1a, which showed low cytotoxicity at 1000 µg/mL (cell viability 50.77 ± 4.67%). In conclusion, the carboxymethyl chitosan derivatives bearing quinoline groups showed remarkable antioxidant ability and weak cytotoxicity, highlighting their potential use in food and medical applications.

Characterization of nano-hydroxyapatite incorporated carboxymethyl chitosan composite on human dental pulp stem cells.

AIM: To compare the odontogenic differentiation potential of a composite scaffold (CSHA) comprising of nano-hydroxyapatite (nHAp) and carboxymethyl chitosan (CMC) with Biodentine on human dental pulp stem cells (hDPSCs). METHODOLOGY: A CSHA scaffold was prepared through an ultrasonication route by adding nHAp and CMC (1:5 w/w) in water medium followed by freeze-drying. Physicochemical characterization was achieved using scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy. In-vitro bioactivity and pH assessments were done by soaking in simulated body fluid (SBF) for 28 days. The angiogenic and odontogenic differentiation abilities were assessed by expression of vascular endothelial growth factor (VEGF) and Dentine sialophosphoprotein (DSPP) markers on cultured hDPSCs by flow cytometry and RT-qPCR at 7, 14 and 21 days. Cell viability/proliferation and biomineralization abilities of CSHA were compared with Biodentine by MTT assay, alkaline phosphatase (ALP) activity, Alizarin Red Staining (ARS) and osteopontin (OPN) expression on hDPSCs following 7 and 14 days. Data were statistically analysed with Kruskal Wallis and Friedman tests as well as one way anova followed by appropriate post hoc tests (p < .05). RESULTS: Characterization experiments revealed a porous microstructure of CSHA with pore diameter ranging between 60 and 200 µm and 1.67 Ca/P molar ratio along with the characteristic functional groups of both HAp and CMC. CSHA displayed bioactivity in SBF by forming apatite-like crystals and maintained a consistent pH value of 7.70 during 28 days' in vitro studies. CSHA significantly upregulated VEGF and DSPP levels on hDPSCs on day 21 compared with day 7 (p < .05). Further, CSHA supported cell viability/proliferation over 14 days like Biodentine with no statistical differences (p > .05). However, CSHA exhibited increased ALP and ARS activity with an intense OPN staining compared with Biodentine after 14 days (p < .05). CONCLUSION: The results highlighted the odontogenic differentiation and biomineralization abilities of CSHA on hDPSCs with significant VEGF and DSPP gene upregulations. Further, CSHA exhibited enhanced mineralization activity than Biodentine, as evidenced by increased ALP, ARS and OPN activity on day 14. The nHAp-CMC scaffold has the potential to act as an effective pulp capping agent; however, this needs to be further validated through in-vivo animal studies.

Evaluation of structural integrity effect on adhesion strength of root dentin with a multi-functional irrigation strategy.

OBJECTIVES: To evaluate effects of a novel auxiliary irrigation strategy, proanthocyanidin (PA) + carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplexes, on maintaining the organic-inorganic structural integrity and hence optimizing the adhesion strength of root dentin. MATERIALS AND METHODS: Dentin specimens (n = 150) were prepared and subjected to the classical irrigating strategy with or without PA and CMC/ACP. The ultrastructure and biomechanical behaviour of dentin were characterized by scanning electron microscopy and atomic force microscope, respectively. Forty single root-canal premolars were employed for push-out bond strength testing. Besides, the antibacterial effects against Enterococcus faecalis were evaluated with confocal laser scanning microscopy. Statistical differences were verified with one-way ANOVA and Tukey's post-tests. RESULTS: The organic-inorganic structural integrity of root dentin was repaired with the synergetic use of PA and CMC/ACP. Correspondingly, the bond stability between the root canal wall and the AH-Plus sealer was significantly reinforced (P < 0.05). Meanwhile, the tissue biomechanical properties and antibacterial behaviour were enhanced compared to that of control group (P < 0.05). CONCLUSIONS: The synergistic utilization of PA and CMC/ACP can preserve the structural integrity of root dentin, contributing to optimizing the sealing effects of root canal. Moreover, the novel irrigation strategy demonstrated a favourable antimicrobial activity. CLINICAL RELEVANCE: The combination of PA and CMC/ACP can serve as a promising auxiliary irrigation strategy to optimize the outcomes of chemical preparation, enhance the sealing effects of root canal and hence improve the success rate of treatment.

The Effect of Ficin Immobilized on Carboxymethyl Chitosan on Biofilms of Oral Pathogens.

In the last decade, Ficin, a proteolytic enzyme extracted from the latex sap of the wild fig tree, has been widely investigated as a promising tool for the treatment of microbial biofilms, wound healing, and oral care. Here we report the antibiofilm properties of the enzyme immobilized on soluble carboxymethyl chitosan (CMCh) and CMCh itself. Ficin was immobilized on CMCh with molecular weights of either 200, 350 or 600 kDa. Among them, the carrier with a molecular weight of 200 kDa bound the maximum amount of enzyme, binding up to 49% of the total protein compared to 19-32% of the total protein bound to other CMChs. Treatment with pure CMCh led to the destruction of biofilms formed by Streptococcus salivarius, Streptococcus gordonii, Streptococcus mutans, and Candida albicans, while no apparent effect on Staphylococcus aureus was observed. A soluble Ficin was less efficient in the destruction of the biofilms formed by Streptococcus sobrinus and S. gordonii. By contrast, treatment with CMCh200-immobilized Ficin led to a significant reduction of the biofilms of the primary colonizers S. gordonii and S. mutans. In model biofilms obtained by the inoculation of swabs from teeth of healthy volunteers, the destruction of the biofilm by both soluble and immobilized Ficin was observed, although the degree of the destruction varied between artificial plaque samples. Nevertheless, combined treatment of oral Streptococci biofilm by enzyme and chlorhexidine for 3 h led to a significant decrease in the viability of biofilm-embedded cells, compared to solely chlorhexidine application. This suggests that the use of either soluble or immobilized Ficin would allow decreasing the amount and/or concentration of the antiseptics required for oral care or improving the efficiency of oral cavity sanitization.

Effects of Chitosan and Cellulose Derivatives on Sodium Carboxymethyl Cellulose-Based Films: A Study of Rheological Properties of Film-Forming Solutions.

Bio-based packaging materials and efficient drug delivery systems have garnered attention in recent years. Among the soluble cellulose derivatives, carboxymethyl cellulose (CMC) stands out as a promising candidate due to its biocompatibility, biodegradability, and wide resources. However, CMC-based films have limited mechanical properties, which hinders their widespread application. This paper aims to address this issue by exploring the molecular interactions between CMC and various additives with different molecular structures, using the rheological method. The additives include O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanocrystals (CNC), and cellulose nanofibers (CNF). By investigating the rheological properties of film-forming solutions, we aimed to elucidate the influencing mechanisms of the additives on CMC-based films at the molecular level. Various factors affecting rheological properties, such as molecular structure, additive concentration, and temperature, were examined. The results revealed that the interactions between CMC and the additives were dependent on the charge of the additives. Electrostatic interactions were observed for HACC and HTCMCh, while O-CMCh, CNC, and CNF primarily interacted through hydrogen bonds. Based on these rheological properties, several systems were selected to prepare the films, which exhibited excellent transparency, wettability, mechanical properties, biodegradability, and absence of cytotoxicity. The desirable characteristics of these selected films demonstrated the strong biocompatibility between CMC and chitosan and cellulose derivatives. This study offers insights into the preparation of CMC-based food packaging materials with specific properties.

Dietary supplementation with nanoparticle CMCS-20a enhances the resistance to GCRV infection in grass carp (Ctenopharyngodon idella).

Combination of antimicrobial proteins and nanomaterials provides a platform for the development of immunopotentiators. Oral administration of immunopotentiators can significantly enhance the immunity of organisms, which provides ideas for disease prevention. In this study, we confirmed that nanoparticles CMCS-20a can efficiently prevent grass carp reovirus (GCRV) infection. Firstly, we verified that CiCXCL20a is involved in the immune responses post GCRV challenge in vivo and alleviates the cell death post GCRV challenge in CIK cells. Then, we prepared nanoparticles CMCS-20a using carboxymethyl chitosan (CMCS) loaded with grass carp (Ctenopharyngodon idella) CXCL20a (CiCXCL20a). Meanwhile, we confirmed nanoparticles CMCS-20a can alleviate the degradation in intestine. Subsequently, we added it to the feed by low temperature vacuum drying method and high temperature spray drying method, respectively. Grass carp were oral administration for 28 days and challenged by GCRV. Low temperature vacuum drying group (LD-CMCS-20a) significantly improve grass carp survival rate, but not high temperature spray drying group (HD-CMCS-20a). To reveal the mechanisms, we investigated the serum biochemical indexes, intestinal mucus barrier, immune gene regulation and tissue damage. The complement component 3 content, lysozyme and total superoxide dismutase activities are highest in LD-CMCS-20a group. LD-CMCS-20a effectively attenuates the damage of GCRV to the number of intestinal villous goblet cells and mucin thickness. LD-CMCS-20a effectively regulates mRNA expressions of immune genes (IFN1, Mx2, Gig1 and IgM) in spleen and head kidney tissues. In addition, LD-CMCS-20a obviously alleviate tissue lesions and viral load in spleen. These results indicated that the nanoparticles CMCS-20a can enhance the disease resistance of fish by improving their immunity, which provides a new perspective for fish to prevent viral infections.

Glutathione-sensitive IPI-549 nanoparticles synergized with photodynamic Chlorin e6 for the treatment of breast cancer.

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2µM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.

Mesenchymal stem cells encapsulation in chitosan and carboxymethyl chitosan hydrogels to enhance osteo-differentiation.

BACKGROUND: Recently biomaterials utilized for designing scaffolds in tissue engineering are not cost-effective and eco-friendly. As a result, we design and develop biocompatible and bioactive hydrogels for osteo-tissue regeneration based on the natural polysaccharide chitosan. Three distinct hydrogel components were used for this. METHODS: Hydrogels networks were created using chitosan 2% (CTS 2%), carboxymethyl chitosan 2% (CMC 2%), and 50:50 mixtures of CTS and CMC (CTS/CMC 50:50). Furthermore, scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), degradation, and swelling behavior of design hydrogels were studied. Also, the cytocompatibility and osteo-differentiation potency were examined by encapsulating mesenchymal stem cells derived from adipose tissue (AMSCs) on the designed hydrogels. RESULTS: According to the findings, our results showed an acceptable pore structure, functional groups, and degradation rate of the designed hydrogels for in vitro evaluation. In addition, employing CMC instead of CTS or adding 50% CMC to the hydrogel component could improve the hydrogel's osteo-bioactivity without the use of external osteogenic differentiation agents. CONCLUSION: The CMC-containing hydrogel not only caused early osteogenesis but also accelerated differentiation to the maturity phase of osteoblasts.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Eggshell derived nano-hydroxyapatite incorporated carboxymethyl chitosan scaffold for dentine regeneration: A laboratory investigation.

AIM: To assess odontogenic differentiation abilities of porous biomineralizable composite scaffolds comprising eggshell derived nano-hydroxyapatite (HAnp) and carboxymethyl chitosan (CMC) on cultured human dental pulp stem cells (hDPSCs). METHODOLOGY: Nano-hydroxyapatite was derived from eggshells using a simple combustion method and CMC was prepared from chitosan through a chemical route. Several compositions of HAnp-CMC (0:5, 5:0, 1:5, 2:5, 3:5, 4:5 and 1:1 w/w%) scaffolds were prepared by magnetic stirring and freeze-drying methods. HAnp-CMC scaffolds were characterized using high-resolution scanning electron microscopy combined with energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction methods. In vitro bioactivity was determined following the interaction in simulated body fluid for 21 days. The optimized composite was then loaded onto hDPSCs to assess cell viability/proliferation, dentine sialophosphoprotein (DSPP) and vascular endothelial growth factor (VEGF) expressions using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, real-time quantitative polymerase chain reaction and flow cytometry methods, respectively, following 7, 14 and 21 days. For intergroup and intragroup comparisons, Kruskal-Wallis and Friedman tests were employed, respectively, followed by appropriate post hoc test (Dunn). Significant levels were set at *p < .05 and *p < .01. RESULTS: Synthesized hydroxyapatite (HAp) comprised crystals ranging from 20 to 50 nm (HAnp) with spherulite morphology and calcium/phosphorus (Ca/P) molar ratio of 1.67. The ultrastructure of all the scaffolds revealed a highly interconnected porous microstructure, whilst the chemical characterization displayed specific functional groups of both HAnp and CMC. In vitro bioactivity assessment confirmed the biomineralization potential of all scaffolds with an apatite-like crystal formation on the surface. The 1:5 HAnp-CMC revealed a favourable pore size (60-180 µm) that was suitable for cell seeding and was chosen for further experiments. Cell viability/proliferation rates of hDPSCs loaded 1:5 HAnp-CMC at 21st day was significantly greater than that at 7th day (p < .05). The mean relative quantification of DSPP expression by the scaffold was significantly higher (p < .05) on day 21 (3.16) than on day 7 (1.67). Mean fluorescence intensity of the VEGF expression at day 21 (32.5) was also significantly higher (p < .01) than at day 7 (12.54). CONCLUSION: hDPSCs on 1:5 HAnp-CMC scaffolds displayed increased cell viability/proliferation and enhanced DSPP as well as VEGF expressions. The 1:5 HAnp-CMC composite has the potential to serve as a promising scaffold for dentine regeneration.

Prospective, randomized, controlled, noninferiority clinical trial to evaluate the safety and efficacy of absorbable macroporous polysaccharide composites as adjunct to hemostasis during open surgery.

BACKGROUND: To address intraoperative bleeding in cardiac surgery, reducing blood transfusion requirements, is mandatory to achieve effective hemostasis. Hemostatic agents may limit localized persistent bleeding. The introduction of carboxymethyl-chitosan component into the hemostatic agent and the application of the radiation crosslinking technique maintain its capacity for achieving intraoperative hemostasis, thus increasing the clinical utility. METHODS: A prospective, noninferiority and randomized controlled clinical trial to compare the safety and efficacy of absorbable macroporous polysaccharide composites (AMPC, treatment group) with compound microporous polysaccharide hemostatic powder (CMPHP, control group) (2:1 ratio) as adjuncts to hemostasis in open surgery. The main indication was used for hemostasis in various traumatic hemorrhage areas, including cardiothoracic, vascular, and general surgery. The primary endpoint was success rate of hemostasis within 300 s (at a 10% noninferiority margin). The secondary endpoint was hemostasis time. Both endpoints were assessed in the modified intention-to-treat (MITT) population. Safety parameters were assessed. This study is fully compliant with the CONSORT statement. RESULTS: Randomized patients in AMPC and CMPHP groups were 168 and 84, respectively. In MITT population, the success rates of hemostasis within 300 s were 98.8% (163 of 165) in AMPC and 94.0% (78 of 83) in CMPHP (treatment difference 4.8% [95% CI -0.57% to 10.20%]). AMPC was thus noninferior to CMPHP. Hemostasis time (median [interquartile range]) with AMPC (87 [52.5, 180] s) was better than CMPHP (110 [54.5, 181] s). Changes in laboratory parameters over time and shifts to abnormal values were typical of surgeries and similar between two groups. No noticeable adverse effects associated with AMPC or CMPHP were observed. CONCLUSIONS: AMPC is well tolerated as topical hemostatic agent, noninferior to commercial CMPHP, and exhibits excellent safety. This study provides a novel hemostatic agent which appears to offer significant clinical advantage in various hemorrhage areas.

Carboxymethyl Chitosan Modified Oxymatrine Liposomes for the Alleviation of Emphysema in Mice via Pulmonary Administration.

Pulmonary emphysema is a fatal lung disease caused by the progressive thinning, enlargement and destruction of alveoli that is closely related to inflammation and oxidative stress. Oxymatrine (OMT), as a bioactive constituent of traditional Chinese herbal Sophora flavescens, has great potential to alleviate pulmonary emphysema via its anti-inflammatory and antioxidative activities. Pulmonary administration is the most preferable way for the treatment of lung diseases. To improve the in vivo stability and pulmonary retention of OMT, OMT-loaded liposome with carboxymethyl chitosan (CMCS) modification was developed. The CMCS was modified on the surface of OMT liposomes via electrostatic attraction and covalent conjugation to obtain Lipo/OMT@CMCS and CMCS-Lipo/OMT, respectively. A porcine pancreatic elastase (PPE)-induced emphysema mice model was established to evaluate the alleviation effects of OMT on alveolar expansion and destruction. CMCS-modified liposomal OMT exhibited superior ameliorative effects on emphysema regardless of the preparation methods, and higher sedimentation and longer retention in the lung were observed in the CMCS-Lipo group. The mechanisms of OMT on emphysema were related to the downregulation of inflammatory cytokines and the rebalancing of antioxidant/oxidation via the Nrf2/HO-1 and NF-κB/IκB-α signaling pathways, leading to reduced cell apoptosis. Moreover, the OMT liposomal preparations further enhanced its anti-inflammatory and antioxidative effects. In conclusion, pulmonary administration of OMT is a potential strategy for the treatment of emphysema and the therapeutic effects can be further improved by CMCS-modified liposomes.

Nerve Regeneration Effect of a Composite Bioactive Carboxymethyl Chitosan-Based Nerve Conduit with a Radial Texture.

Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.

Enhancement of Antioxidant Property of N-Carboxymethyl Chitosan and Its Application in Strawberry Preservation.

Bio-enzymatic grafting phenolic acid to chitosan derivative is an efficient and environmentally friendly molecular synthesis technology. In the present study, N-carboxymethyl chitosan (CMCS) was grafted with gallic acid (GA) using recombinant bacterial laccase from Streptomyces coelicolor as a catalyst. GA and CMCS were successfully grafted as determined by measuring amino acid content, Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy. Then, the effect of GA-g-CMCS coating on the freshness of strawberries at 20 ± 2 °C was explored. The physiological and biochemical quality indicators of strawberries during storage were monitored. The 1.5% GA-g-CMCS coating helped to protect the antioxidant properties and nutrients of strawberries and extend the shelf life. Specifically, it reduced the weight loss of strawberries during preservation (originally 12.7%) to 8.4%, maintained titratable acidity content (TA) residuals above 60% and reduced decay rate from 36.7% to 8.9%. As a bioactive compound, GA-g-CMCS has the potential to become an emerging food packing method. These results provide a theoretical basis and reference method for the subsequent synthesis and application of CMCS derivatives.

Detailed Structural Characterization of Oxidized Sucrose and Its Application in the Fully Carbohydrate-Based Preparation of a Hydrogel from Carboxymethyl Chitosan.

Oxidized sucrose (OS) is a bio-based cross-linking agent with excellent biological safety and environmental non-toxicity. However, the precise structure of OS has not been elucidated owing to its structural complexity and low purity. Accordingly, in this study, complete chemical shift assignments were performed by applying various nuclear magnetic resonance techniques, which permitted the structural and quantitative characterization of the two main OS products, each of which contained four aldehyde groups. In addition, we investigated the use of OS as a cross-linking agent in the preparation of a hydrogel from carboxymethyl chitosan (CMC), one of the most popular polysaccharides for use in biomedical applications. The primary amine groups of CMC were immediately cross-linked with the aldehyde groups of OS to form hydrogels without the requirement for a catalyst. It was found that the degree of cross-linking could be easily controlled by the feed amount of OS during CMC hydrogel preparation and the final cross-linking degree affected the thermal, swelling, and rheological properties of the obtained hydrogel. The results presented in this study are therefore expected to be applicable in the preparation of fully carbohydrate-based hydrogels for medical and pharmaceutical applications.