Bioinspired wet adhesive carboxymethyl cellulose-based hydrogel with rapid shape adaptability and antioxidant activity for diabetic wound repair.

Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.

Bio-nanocomposite active packaging films based on carboxymethyl cellulose, myrrh gum, TiO2 nanoparticles and dill essential oil for preserving fresh-fish (Cyprinus carpio) meat quality.

This study developed a composite film for packaging refrigerated common carp fillets using carboxymethyl cellulose (CMC) (1.5 % w/v)/Myrrh gum (MG) (0.25 % w/v) base with the addition of titanium dioxide nanoparticles (TiO2 NPs) (0.25 %, 0.5 %, and 1 %) and Dill essential oil (DEO) (1.5 %, 2.25 %, and 3 %). The film was produced using a casting method and optimized for mechanical and barrier properties. The incorporation of DEO and TiO2 NPs into CMC/MG composite films significantly reduced moisture content (MC) and water vapor permeability (WVP), improved their tensile strength (TS), and increased their antimicrobial and antioxidant properties. Moreover, MG can improve the physicomechanical properties of the CMC/MG composite films. The film components had good compatibility without significant aggregation or cracks. In conclusion, the optimized CMC/MG (1.5 %/0.25 %) film containing TiO2 NPs (0.5 %), and DEO (2.25 %) has the best overall performance and can be a good source for making edible film. Functionally, this bioactive nanocomposite film significantly increased the shelf life of refrigerated fish fillet samples for 12 days by inhibiting microbial growth and reducing the oxidation rate compared to the control sample. The knowledge obtained from this study can guide the development of bio-nanocomposite and biodegradable food packaging films based on CMC/MG to increase the shelf life of food products and environmental protection.

Enhancing maize resilience to drought stress: the synergistic impact of deashed biochar and carboxymethyl cellulose amendment.

Drought stress poses a significant challenge to maize production, leading to substantial harm to crop growth and yield due to the induction of oxidative stress. Deashed biochar (DAB) in combination with carboxymethyl cellulose (CMC) presents an effective approach for addressing this problem. DAB improves soil structure by increasing porosity and water retention and enhancing plant nutrient utilization efficiency. The CMC provides advantages to plants by enhancing soil water retention, improving soil structure, and increasing moisture availability to the plant roots. The present study was conducted to investigate the effects of DAB and CMC amendments on maize under field capacity (70 FC) and drought stress. Six different treatments were implemented in this study, namely 0 DAB + 0CMC, 25 CMC, 0.5 DAB, 0.5 DAB + 25 CMC, 1 DAB, and 1 DAB + 25 CMC, each with six replications, and they were arranged according to a completely randomized design. Results showed that 1 DAB + 25 CMC caused significant enhancement in maize shoot fresh weight (24.53%), shoot dry weight (38.47%), shoot length (32.23%), root fresh weight (19.03%), root dry weight (87.50%) and root length (69.80%) over control under drought stress. A substantial increase in maize chlorophyll a (40.26%), chlorophyll b (26.92%), total chlorophyll (30.56%), photosynthetic rate (21.35%), transpiration rate (32.61%), and stomatal conductance (91.57%) under drought stress showed the efficiency of 1 DAB + 25 CMC treatment compared to the control. The enhancement in N, P, and K concentrations in both the root and shoot validated the effectiveness of the performance of the 1 DAB + 25 CMC treatment when compared to the control group under drought stress. In conclusion, it is recommended that the application of 1 DAB + 25 CMC serves as a beneficial amendment for alleviating drought stress in maize.

A ternary composite hydrogel based on sodium alginate, carboxymethyl cellulose and copper-doped 58S bioactive glass promotes cutaneous wound healing in vitro and in vivo.

Hydrogels offer a novel approach to wound repair. In this study, we synthesized a ternary composite using sodium alginate (SA), carboxymethyl cellulose (CMC) and copper-doped 58S bioactive glass (BG). According to our mechanical testing results, the composite made of 7 wt% CMC and 7 wt% BG (SA-7CMC-7BG) showed optimal properties. In addition, our in vitro studies revealed the biocompatibility and bioactivity of SA-7CMC-7BG, with a negative zeta potential of -31.7 mV. Scanning electron microscope (SEM) images showed 273-µm-diameter pores, cell adhesion, and anchoring. The SA-7CMC-7BG closed 90.4 % of the mechanical scratch after 2 days. An in vivo wound model using Wistar rats showed that SA-7CMC-7BG promoted wound healing, with 85.57 % of the wounds healed after 14 days. Treatment with the SA-7CMC-7BG hydrogel caused a 1.6-, 65-, and 1.87-fold increase in transforming growth factor beta (TGF-ß), Col I, and vascular endothelial growth factor (VEGF) expression, respectively that prevents fibrosis and promotes angiogenesis. Furthermore, interleukin 1ß (IL-1ß) expression was downregulated by 1.61-fold, indicating an anti-inflammatory effect of SA-7CMC-7BG. We also observed an increase in epidermal thickness, the number of fibroblast cells, and collagen deposition, which represent complementary pathology results confirming the effectiveness of the SA-7CMC-7BG hydrogel in cutaneous wound healing.

Study on Synergistic Effects of Nanohydroxyapatite/High-Viscosity Carboxymethyl Cellulose Scaffolds Stimulated by LIPUS for Bone Defect Repair of Rats.

Despite the self-healing capacity of bone, the regeneration of critical-size bone defects remains a major clinical challenge. In this study, nanohydroxyapatite (nHAP)/high-viscosity carboxymethyl cellulose (hvCMC, 6500 mPa·s) scaffolds and low-intensity pulsed ultrasound (HA-LIPUS) were employed to repair bone defects. First, hvCMC was prepared from ramie fiber, and the degree of substitution (DS), purity, and content of NaCl of hvCMC samples were 0.91, 99.93, and 0.017%, respectively. Besides, toxic metal contents were below the permissible limits for pharmaceutically used materials. Our results demonstrated that the hvCMC is suitable for pharmaceutical use. Second, nHAP and hvCMC were employed to prepare scaffolds by freeze-drying. The results indicated that the scaffolds were porous, and the porosity was 35.63 ± 3.52%. Subsequently, the rats were divided into four groups (n = 8) randomly: normal control (NC), bone defect (BD), bone defect treated with nHAP/hvCMC scaffolds (HA), and bone defect treated with nHAP/hvCMC scaffolds and stimulated by LIPUS (HA-LIPUS). After drilling surgery, nHAP/hvCMC scaffolds were implanted in the defect region of HA and HA-LIPUS rats. Meanwhile, HA-LIPUS rats were treated by LIPUS (1.5 MHz, 80 mW cm-2) irradiation for 2 weeks. Compared with BD rats, the maximum load and bone mineral density of HA-LIPUS rats were increased by 20.85 and 51.97%, respectively. The gene and protein results indicated that nHAP/hvCMC scaffolds and LIPUS promoted the bone defect repair and regeneration of rats significantly by activating Wnt/ß-catenin and inhibiting OPG/RANKL signaling pathways. Overall, compared with BD rats, nHAP/hvCMC scaffolds and LIPUS promoted bone defect repair significantly. Furthermore, the research results also indicated that there are synergistic effects for bone defect repair between the nHAP/hvCMC scaffolds and LIPUS.

Layer by layer application of chitosan and carboxymethyl cellulose coatings delays ripening of mango fruit by suppressing cell wall polysaccharides disassembly.

Mango is a climacteric fruit that ripens quickly after harvest due to its climacteric nature. Edible coatings have been reported to delay the ripening of various harvested fruit. The efficacy of the applied edible coatings could be improved by using in combination as a layer-by-layer (LBL) approach. So, the influence of LBL application of chitosan (CH) and carboxymethyl cellulose (CMC) was studied on mangoes during postharvest storage at 15 °C for 20 days. Mangoes were coated with monolayers of CH (1 % w/v) and CMC (1 % w/v) as well as LBL application of CH and CMC and were compared with control. The treatment of mangoes with CH and CMC-based LBL treatment resulted in lower decay percentage and weight loss along with higher total chlorophyll pigments and suppressed total carotenoid accumulation. The LBL application of CH and CMC showed lower activity of chlorophyll degrading such as chlorophyllase (CPS), pheophytinase (Phe), Mg-dechalatase (MGD) and chlorophyll degrading peroxidase (Chl-POD) enzymes as well as reduced changes in b*, a* and L* along with a suppressed increase in ethylene (EP) and CO2 production (CPR) rates having higher antioxidant such as catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD) and superoxide dismutase (SOD) enzymes activity. In addition, mangoes coated with LBL treatment of CH and CMC exhibited lower water-soluble pectin (WSP) and higher protopectin (PP) having higher concentrations of chelate soluble (CSP) and sodium carbonate-soluble pectin (SCP). Similarly, LBL-coated mangoes showed significantly higher hemicellulose (HCLS) and cellulose (CLS) contents in contrast with control. It was observed that mangoes coated with CH and CMC-based LBL coating exhibited higher flesh firmness and showed suppressed cellulase (CS), pectin methylesterase (PME), polygalacturonase (PG) and ß-galactosidase (ß-Gal) enzymes activity. The concentrations of total soluble solids and ripening index were markedly lower and titratable acidity was higher in the LBL-based coating treatment in comparison with control. In conclusion, LBL treatment based on CH and CMC coatings could be used for the delay of ripening and softening of harvested mangoes.

Gelatin/carboxymethylcellulose composite film combined with photodynamic antibacterial: New prospect for fruit preservation.

Plastic packaging causes environmental pollution, and the development of simple and effective biodegradable active packaging remains a challenge. In this study, gelatin (G) and sodium carboxymethylcellulose (CMC) were used as film materials, with the addition of curcumin (Cur), a photosensitive substance, to investigate the changes in the physical and chemical properties of the film and its application in fruit preservation. The results demonstrated that Cur was compatible with the film. With the addition of Cur, the thickness of the film increased up to 1.3 times, while the moisture content was reduced to 12.10 %. The tensile strength (TS) and elongation at break (EAB) of the film can reach 8.84 MPa and 19.33 %, respectively. The photodynamic antibacterial experiment revealed that the film containing 0.5 % Cur exhibited the highest antibacterial rate, reaching 99.99 % against Staphylococcus aureus (S. aureus) and 95 % against Escherichia coli (E. coli). During storage, the grapes remained unspoiled for up to 9 days after being phototreated with the film and the microbial content of the skin was much lower than that of the control group. In addition, Cur provided antioxidant activity for the film, with a scavenging activity of 39.54 % against the 2,2-diphenyl-1-picrind radical (DPPH). Bananas exposed to the film-forming solution for a short period of time remained fresh for up to 6 days. During preservation, the weight of the treated bananas decreased more slowly than that of the control group. In addition, the activity of SOD on the 7th day was approximately 20 U/g higher than that of the control group, which helped to reduce oxidative stress during banana preservation. In summary, G-CMC/Cur film is an optional fruit-cling film that can be used in food packaging.

Biogenic synthesis of dopamine/carboxymethyl cellulose/TiO2 nanoparticles using Psidium guajava leaf extract with enhanced antimicrobial and anticancer activities.

The green synthesis of metal oxide nanoparticles (NPs) has garnered considerable attention from researchers due to its utilization of eco-friendly solvents during synthesis and cost-effective approaches. This study focuses on the synthesis of titanium oxide (TiO2) and dopamine (DA) carboxymethyl cellulose (CMC)-doped TiO2 (DA/CMC/TiO2) NP using Psidium guajava leaf extract, while also investigating the structural, optical, and morphological and biocidal potential of the prepared NPs. Significantly larger zones of inhibition were observed for DA/CMC/TiO2 NPs compared to TiO2 against various pathogens. Moreover, the MTT assay was carried out to evaluate the anticancer activity of the prepared samples against MG-63 cells, and the results revealed that DA/CMC/TiO2 NPs exhibited significantly higher level of anticancer activity compared to TiO2. The experimental results demonstrated that DA/CMC/TiO2 NPs exhibited enhanced anticancer activity in a dose-dependent manner when compared to TiO2 NPs.

Facile fabrication of carboxymethylcellulose/ZnO/g-C3N4 containing nutmeg extract with photocatalytic performance for infected wound healing.

New topical antibacterial agents are required to inhibit and development of bacteria and also promoting the wound healing process. This study was evaluating the healing effect of Myristica fragrans extract coated with carboxymethyl cellulose, zinc oxide and graphite carbon nitride (CMC/ZnO/g-C3N4/MyR) by photocatalytic process on the healing process of full-thickness infectious excision wounds in mice. Nanosheets were prepared and physicochemical properties were evaluated. Safety, in vitro release, antibacterial activities under in vitro and in vivo condition, wound contraction, histopathological properties and the protein expressions of tumor necrosis factor-α (TNF-α), collagen 1A (COL1A) and CD31 were also evaluated. Physicochemical properties confirmed their successful synthesis. Nanosheets exhibited antibacterial activity under in vitro and in vivo conditions. The formulations containing CMC/ZnO/g-C3N4/MyR, significantly (P < 0.05) competed with standard ointment of mupirocin for accelerating the wound healing process due to their effects on bacterial count and the expression of TNF-α and also accelerating the proliferative phase. This structure can be used as a safe structure in combination with other agents for accelerating the wound healing process following future clinical studies.

Carboxymethylcellulose/Agar-Based Multifunctional Films Incorporated with Zn-Doped SnO2 Nanoparticles for Active Food Packaging Application.

SnO2 and Zn-SnO2 nanoparticles were prepared by chemical precipitation, and the rutile phase of SnO2 was confirmed through X-ray diffraction studies. X-ray photoelectron spectroscopy (XPS) confirmed the doping of SnO2 with Zn and elucidated the surface chemistry before and after doping. The average sizes of SnO2 and Zn-SnO2 nanoparticles determined using TEM were 3.96 ± 0.85 and 3.72 ± 0.9 nm, respectively. UV-visible and photoluminescence spectrophotometry were used to evaluate the optical properties of SnO2 and Zn-SnO2 nanoparticles, and their energy gaps (Eg) were 3.8 and 3.9 eV, respectively. The antibacterial activity of these nanoparticles against Salmonella enterica and Staphylococcus aureus was evaluated under dark and light conditions. Antibacterial activity was higher in light, showing the highest activity (99.5%) against S. enterica. Carboxymethylcellulose (CMC)/agar-based functional composite films were prepared by adding different amounts of SnO2 and Zn-SnO2 nanoparticles (1 and 3 wt % of polymers). The composite film showed significantly increased UV barrier properties while maintaining the mechanical properties, water vapor barrier, and transparency compared to the neat CMC/agar film. These composite films showed significant antibacterial activity; however, the Zn-SnO2-added film showed stronger antibacterial activity (99.2%) than the SnO2-added film (15%).

Decellularized allogeneic cartilage paste with human costal cartilage and crosslinked hyaluronic acid-carboxymethyl cellulose carrier augments microfracture for improved articular cartilage repair.

Articular cartilage lacks natural healing abilities and necessitates surgical treatments for injuries. While microfracture (MF) is a primary surgical approach, it often results in the formation of unstable fibrocartilage. Delivering hyaline cartilage directly to defects poses challenges due to the limited availability of autologous cartilage and difficulties associated with allogeneic cartilage delivery. We developed a decellularized allogeneic cartilage paste (DACP) using human costal cartilage mixed with a crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC) carrier. The decellularized allogeneic cartilage preserved the extracellular matrix and the nanostructure of native hyaline cartilage. The crosslinked HA-CMC carrier provided shape retention and moldability. In vitro studies confirmed that DACP did not cause cytotoxicity and promoted migration, proliferation, and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. After 6 months of implantation in rabbit knee osteochondral defects, DACP combined with MF outperformed MF alone, demonstrating improved gait performance, defect filling, morphology, extracellular matrix deposition, and biomechanical properties similar to native cartilage. Thus, DACP offers a safe and effective method for articular cartilage repair, representing a promising augmentation to MF. STATEMENT OF SIGNIFICANCE: Directly delivering hyaline cartilage to repair articular cartilage defects is an ideal treatment. However, current allogeneic cartilage products face delivery challenges. In this study, we developed a decellularized allogeneic cartilage paste (DACP) by mixing human costal cartilage with crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC). DACP preserves extracellular matrix components and nanostructures similar to native cartilage, with HA-CMC ensuring shape retention and moldability. Our study demonstrates improved cartilage repair by combining DACP with microfracture, compared to microfracture alone, in rabbit knee defects over 6 months. This is the first report showing better articular cartilage repair using decellularized allogeneic cartilage with microfracture, without the need for exogenous cells or bioactive substances.

In vitro-in vivo wound healing efficacy of Tridax Procumbens extract loaded Carboxymethylcellulose film.

In this work, Tridax Procumbens Extracts (TPE) were blended with Carboxymethylcellulose (CMC), and film was developed through the casting method. The phytochemical screening of the TPE/CMC film was carried out and found the presence of carbohydrates, tannins, saponins, and cardiac glycosides. The presence of elements such as C, O, Na, P, Cl, K, Ca, Mn, and Nb in TP/CMC film was confirmed through EDX. The melting point of the film was found around 291 ± 0.5 °C which was determined through the DSC curve. The maximum tensile strength of the TPE/CMC was found as 14 ± 0.5 MPa. The film showed antibacterial activity against Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Vibrio cholera compared to the control. Cell viability study exhibited 95 % and 98 % cell proliferation for the test film after interacting with the L929 cell line for 18 h and 24 h. The optical contact angle of the TPE/CMC film was also determined. The in-vivo, wound healing studies on adult mice showed healing within 10 days only and the histopathological results revealed the maximum number of fibroblasts with a high density of collagen fibers in the test group indicating that the prepared film can be an effective wound dressing material.

Preparation and activity of sodium carboxymethyl cellulose (CMC-Na) and Metarhizium rileyi ZHKUMR1 composite membrane.

Improving the adhesion capability of Metarhizium rileyi ZHKUMR1 on leaves enabled by the combination with Carboxymethyl Cellulose (CMCNa) materials is feasible to improve the utilization rate of Metarhizium rileyi. Herein, the CMC-Na-ZHKUMR1 membrane was prepared by simply mixing Carboxymethyl Cellulose (CMCNa) with Metarhizium rileyi. Through compatibility test, it was found that the inhibition rates of spore germination and mycelial growth of ZHKUMR1 were only 1.51 % and 3.13 % when the concentration of Carboxymethyl Cellulose (CMCNa) was 0.5 %. By adding 2 % of Carboxymethyl Cellulose (CMCNa) under UV irradiation for 30 min, the protective rate of spore germination of ZHKUMR1 was up to ~12.44 %, where the wettability on corn leaves was achieved and the retention of ZHKUMR1 spores on corn leaves was increased. After indoor activity determination, it was found that after 3 min of simulated rain washing, the lethal rate of corn leaves pretreated with CMC-Na-ZHKUMR1 on the 2nd instar larvae of Spodoptera frugiperda was 46.67 %, which was much higher than that of ZHKUMR1 spore suspension alone. This work clearly showed that Carboxymethyl Cellulose (CMCNa) effectively improved the field application effect of Metarhizium rileyi ZHKUMR1, and this strategy provided guidance for improving the field efficacy of Metarhizium rileyi ZHKUMR1.

A novel multifunctional chitosan-gelatin/carboxymethyl cellulose-alginate bilayer hydrogel containing human placenta extract for accelerating full-thickness wound healing.

The replication of skin's dermal and epidermal morphology within a full-thickness wound using a bi-layer hydrogel to cater to their distinct needs is a compelling pursuit. Moreover, human placenta extract (HPE), containing a diverse array of bioactive agents, has proven to be effective in promoting the wound healing process and enhancing epidermal keratinocytes. This study presents a multifunctional bi-layer hydrogel incorporating HPE for accelerating full-thickness wound healing through sustained HPE release, inhibition of bacteria invasion, and promotion of cell proliferation. The upper layer of the scaffold, known as the dressing layer, is composed of carboxymethyl cellulose and sodium alginate, serving as a supportive layer for cell proliferation. The under layer, referred to as the regenerative layer, is composed of chitosan and gelatin, providing an extracellular matrix-like, porous, moist, and antibacterial environment for cell growth. The scaffold was optimized to replicate the morphology of the dermal and epidermal layers, with suitable fibroblast infiltration and a pore size of approximately 283µm. Furthermore, the degradation rate of the samples matched the wound healing rate and persisted throughout this period. The sustained HPE release rate, facilitated by the degradation rate, was optimized to reach ~98% after 28 days, covering the entire healing period. The samples demonstrated robust antibacterial capabilities, with bacterial inhibition zone diameters of and 2.63±0.12cm for S. aureus and E. coli, respectively. The biocompatibility of the samples remained at approximately 68.33±4.5% after 21 days of fibroblast cell culture. The in vivo experiment indicated that the HPE@Bilayer hydrogel promotes the formation of new blood vessels and fibroblasts during the early stages of healing, leading to the appropriate formation of granulation tissue and a wound contraction rate of (79.31±3.1)%. Additionally, it resulted in the formation of a thick epidermal layer (keratinization) that effectively covered all the impaired areas, achieving a wound contraction rate of 95.83±6.3% at the late stage of wound healing. Furthermore, immunohistochemistry staining for CD31 and TGF-ß revealed that the HPE@Bilayer group had 22 blood vessels/field and 34%-66% immunoactive cells, respectively, after 14 days of healing. However, by day 21, angiogenesis and TGF-ß expression had declined, demonstrating that the wounds had been successfully treated with minimal scarring.

Synergistic amalgamation of shellac with self-antibacterial hydroxyapatite and carboxymethyl cellulose: An interactive wound dressing for ensuring safety and efficacy in preliminary in vivo studies.

This study focuses on the synergistic formulation of environmentally friendly blended materials based on carboxymethyl cellulose (CMC) for advanced interactive wound dressing. New CMC hydrogels were prepared with two degrees of functionalization and chemically crosslinked with citric acid (CA) to fine-tune their properties. Additionally, CMC-based hybrids were created by blending with shellac (SHL) and incorporating self-antibacterial hydroxyapatite (HA) to inhibit bacterial growth and promote wound healing. The results demonstrate the successful production of superabsorbent hydrogels with typical swelling degrees ranging from 81% in water to 82% in phosphate-buffered saline (PBS). These hydrogels exhibit distinct morphological features and remarkable improvements in surface mechanical properties, specifically in their tensile properties, which show a significant increase from approximately 0.03 to 2.2 N/mm2 due to the formation of CMC-SHL-HA hybrid nanostructures. Furthermore, the cytocompatibility of these CMC-based hydrogels was investigated by assessing the in vitro cell viability responses of human skin fibroblasts. The results reveal the cell viability responses over 91%, indicating their biocompatibility with human cells. Moreover, the characteristics of surgical wounds were assessed before and after the application of the hydrogel on dogs, and no signs of infection were observed at any of the surgical sites post-surgery.

Phosphorylated PKM2 regulates endothelium-dependent vasodilation in diabetes. / ç£·é ¸åŒ–PKM2è°ƒæŽ§ç³–å°¿ç— å† çš®ä¾èµ–æ€§è¡€ç®¡èˆ’å¼ åŠŸèƒ½.

OBJECTIVES: Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy. METHODS: The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 µmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels. RESULTS: Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05). CONCLUSIONS: p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.

Injectable hydrogel based on silk fibroin/carboxymethyl cellulose/agarose containing polydopamine functionalized graphene oxide with conductivity, hemostasis, antibacterial, and anti-oxidant properties for full-thickness burn healing.

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing.

Sulfated carboxymethylcellulose mediated enhancement of Timp3 efficacy synergistically attenuates osteoarthritis through inhibition of NFκB and JNK.

Osteoarthritis (OA) is a prevalent degenerative joint condition with no effective disease modifying treatments. In this study, we aimed to address multiple OA hallmarks using a combination of pro-chondrogenic sulfated carboxymethylcellulose (sCMC) and anti-catabolic tissue inhibitor of metalloproteases 3 (Timp3) in relevant disease systems. Firstly, we chemically sulfated carboxymethylcellulose to impart a negative charge and improve the stability of cationic Timp3. The modified sCMC exhibited a molecular weight of 10 kDa and a degree of sulfation of ∼10 %. We further demonstrated that sulfation of CMC confers pro-chondrogenic characteristics. Subsequently, we demonstrated that the combination of sCMC and Timp3 effectively reduced key OA hallmarks, such as matrix degradation, inflammation, and protease expression, in a goat ex vivo OA model compared to individual treatments. We further demonstrated that the anti-OA effect of sCMC and Timp3 is mediated through the suppression of NFκB and JNK activation. To validate the clinical potential and mechanism of action, we conducted experiments on human OA explants. The combination treatment synergistically reduced the expression of MMP13 and NFκB in human OA explants. Overall, sCMC-mediated enhancement of Timp3 efficacy synergistically reduced OA-like traits and demonstrates the potential for OA amelioration.

Nisin:Carboxymethylcellulose polyion complex (PIC) nanoparticles. Preparation and antimicrobial activity.

Nisin is a cationic antimicrobial peptide used as a natural food preservative against gram-positive bacteria. However, nisin is degraded following interaction with food components. Here, we report the first use of Carboxymethylcellulose (CMC), a versatile and affordable food additive, to protect nisin and extend its antimicrobial activity. First, we optimized the methodology by considering the effect of nisin:CMC ratio, pH, and, especially, the degree of substitution of CMC. In particular, we show here how these parameters affected the size, charge, and, notably, the encapsulation efficiency of these nanomaterials. This way, optimized formulations contained over 60 % w/w in nisin while encapsulating ∼90 % of the nisin used. We then show that these new nanomaterials inhibited the growth of Staphylococcus aureus, a major foodborne pathogen, using milk as a representative food matrix. Remarkably, this inhibitory effect was observed with one-tenth of the concentration of nisin currently used in dairy products. We believe that the combination of the affordability of CMC, flexibility and simplicity of preparation, and the ability to inhibit the growth of food pathogens, makes these nisin:CMC PIC nanoparticles an ideal platform to underpin new nisin formulations.

Oxidized carboxymethyl cellulose/gelatin in situ gelling hydrogel for accelerated diabetic wound healing: Synthesis, characterization, and in vivo investigations.

Diabetic wounds are chronic wounds that are currently affecting many patient's quality of life. These wounds are challenging because of the impaired healing cycle and harsh environment. In this study in situ gelling hydrogels based on oxidized carboxymethyl cellulose (OCMC) and gelatin (Gel) were used to hasten the healing rate due to their ease of application. The suggested system in this work is synthesized from entirely natural renewable biomaterials to not only achieve the best biocompatibility and biodegradability but also to develop a sustainable product. The rheological studies showed that the hydrogel is turned into a gel after about 30 s of the mixing process. Moreover, the hydrogel can absorb about ten times its weight, keeping the wound hydrated. In vitro biological investigations indicated optimal biocompatibility, antibacterial, and antioxidant activity for faster tissue regeneration. This product was tested in vivo on normal rats and diabetic mice models to treat full-thickness incisional wounds. Results showed that the OCMC-Gel hydrogel is able to hasten the healing rate in both non-diabetic and diabetic wounds. Pathological examinations of the regenerated skin tissue revealed that the OCMC-Gel treated groups developed much more than the control group.