An antibacterial biologic patch based on bacterial cellulose for repair of infected hernias.

Infection-associated complications and repair failures and antibiotic resistance have emerged as a formidable challenge in hernia repair surgery. Consequently, the development of antibiotic-free antibacterial patches for hernia repair has become an exigent clinical necessity. Herein, a GBC/Gel/LL37 biological patch (biopatch) with exceptional antibacterial properties is fabricated by grafting 2-Methacryloyloxyethyl trimethylammonium chloride (METAC), a unique quaternary ammonium salt with vinyl, onto bacterial cellulose (GBC), followed by compounding with gelatin (Gel) and LL37. The GBC/Gel/LL37 biopatch exhibits stable swelling capacity, remarkable mechanical properties, flexibility, and favorable biocompatibility. The synergistic effect of METAC and LL37 confers upon the GBC/Gel/LL37 biopatch excellent antibacterial efficacy against Staphylococcus aureus and Escherichia coli, effectively eliminating invading bacteria without the aid of exogenous antibiotics in vivo while significantly reducing local acute inflammation caused by infection. Furthermore, the practical efficacy of the GBC/Gel/LL37 biopatch is evaluated in an infected ventral hernia model, revealing that the GBC/Gel/LL37 biopatch can prevent the formation of visceral adhesions, facilitate the repair of infected ventral hernia, and effectively mitigate chronic inflammation. The prepared antibacterial GBC/Gel/LL37 biopatch is very effective in dealing with the risk of infection in hernia repair surgery and offers potential clinical opportunities for other soft injuries, exhibiting considerable clinical application prospects.

Highly elastic, fatigue-resistant, antibacterial, conductive, and nanocellulose-enhanced hydrogels with selenium nanoparticles loading as strain sensors.

The fabrication of highly elastic, fatigue-resistant and conductive hydrogels with antibacterial properties is highly desirable in the field of wearable devices. However, it remains challenging to simultaneously realize the above properties within one hydrogel without compromising excellent sensing ability. Herein, we fabricated a highly elastic, fatigue-resistant, conductive, antibacterial and cellulose nanocrystal (CNC) enhanced hydrogel as a sensitive strain sensor by the synergistic effect of biosynthesized selenium nanoparticles (BioSeNPs), MXene and nanocellulose. The structure and potential mechanism to generate biologically synthesized SeNPs (BioSeNPs) were systematically investigated, and the role of protease A (PrA) in enhancing the adsorption between proteins and SeNPs was demonstrated. Additionally, owing to the incorporation of BioSeNPs, CNC and MXene, the synthesized hydrogels showed high elasticity, excellent fatigue resistance and antibacterial properties. More importantly, the sensitivity of hydrogels determined by the gauge factor was as high as 6.24 when a high strain was applied (400-700 %). This study provides a new horizon to synthesize high-performance antibacterial and conductive hydrogels for soft electronics applications.

Preparation and assessment of agar/TEMPO-oxidized bacterial cellulose cryogels for hemostatic applications.

In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material.

Wet-type grinder-treated okara modulates gut microbiota composition and attenuates obesity in high-fat-fed mice.

Wet-type grinder (WG) is a nanofiber technology used to atomize dietary fiber-rich materials. WG-treated okara (WGO) exhibits high dispersion and viscosity similar to those of viscous soluble dietary fibers. Here, we studied the effect of WGO supplementation on obesity and gut microbiota composition in high-fat diet (HFD)-fed mice. WGO intake suppressed body weight gain and fat accumulation, improved glucose tolerance, lowered cholesterol levels, and prevented HFD-induced decrease in muscle mass. WGO supplementation also led to cecum enlargement, lower pH, and higher butyrate production. The bacterial 16S ribosomal RNA genes (16S rDNA) were sequenced to determine the gut microbiota composition of the fecal samples. Sequencing of bacterial 16S rDNA revealed that WGO treatment increased the abundance of butyrate producer Ruminococcus and reduced the abundances of Rikenellaceae, Streptococcaceae, and Prevotellaceae, which are related to metabolic diseases. Metabolomics analysis of the plasma of WGO- and cellulose-treated mice were conducted using ultra-high-performance liquid chromatography-mass spectrometry. Metabolic pathway analysis revealed that the primary bile acid biosynthesis pathway was significantly positively regulated by WGO intake instead of cellulose. These results demonstrate that WG is useful for improving functional properties of okara to prevent metabolic syndromes, including obesity, diabetes, and dyslipidemia.

An antibacterial membrane based on Janus bacterial cellulose with nano-sized copper oxide through polydopamine conjugation for infectious wound healing.

Bacterial cellulose (BC) produced by Acetobacter xylinum has great advantages in wound dressing. However, the structural limitation under static culture, and lack of antibacterial properties restrict its application, especially for infectious wound healing. The present study reported an original wound dressing, which was composed of a Janus BC membrane with antibacterial nano-sized copper oxide (CuO) through polydopamine (PDA) conjugation to promote wound healing under infectious condition. The finished product (CuO/PDA/BC membrane) exhibited favorable air permeability, high hydrophilicity and good mechanical properties, as well as strong antibacterial effects by the sustained release of CuO and photothermal effect of CuO/PDA. Furthermore, CuO/PDA/BC membrane inhibited inflammatory response and promoted wound healing in an infectious wound model in vivo. These results suggested that our CuO/PDA/BC membrane had great potential as wound dressing for infectious wound healing.

Amphiphilic nanofibrillated cellulose/polyurethane composites with antibacterial, antifouling and self-healing properties for potential catheter applications.

This study focuses on enhancing interventional medical devices, specifically catheters, using a novel composite material. Challenges like corrosion and contamination in vivo, often caused by body fluids' pH, bacteria, and proteins, lead to mechanical damage, bacterial colonization, and biofilm formation on devices like catheters. The objective of this study was to prepare a versatile composite (HFs) by designing polyurethanes (HPU) with an ionic chain extender (HIID) and blending them with amphiphilic nanofibrillated cellulose (Am-CNF). The composite leverages dynamic interactions such as hydrogen bonding and electrostatic forces, as evidenced by Molecular Mechanics (MM) calculations. The H4F0.75 composite exhibited exceptional properties: 99 % length recovery post 600 stretching cycles at 100 % strain, rapid self-healing in artificial urine, high bactericidal activity, and excellent cell viability. Moreover, mechanical aging tests and UV-vis spectral analysis confirmed the material's durability and safety. These findings suggest that the HFs composite holds significant promise for improving catheters' performance in medical applications.

Highly crystalline cellulose microparticles from dealginated seaweed waste ameliorate high fat-sugar diet-induced hyperlipidemia in mice by modulating gut microbiota.

The effects of seaweed cellulose (SC) on high fat-sugar diet (HFSD)-induced glucolipid metabolism disorders in mice and potential mechanisms were investigated. SC was isolated from dealginated residues of giant kelp (Macrocystis pyrifera), with a crystallinity index of 85.51 % and an average particle size of 678.2 nm. Administering SC to C57BL/6 mice at 250 or 500 mg/kg BW/day via intragastric gavage for six weeks apparently inhibited the development of HFSD-induced obesity, dyslipidemia, insulin resistance, oxidative stress and liver damage. Notably, SC intervention partially restored the structure and composition of the gut microbiota altered by the HFSD, substantially lowering the Firmicutes to Bacteroidetes ratio, and greatly increasing the relative abundance of Lactobacillus, Bifidobacterium, Oscillospira, Bacteroides and Akkermansia, which contributed to improved short-chain fatty acid (SCFA) production. Supplementing with a higher dose of SC led to more significant increases in total SCFA (67.57 %), acetate (64.56 %), propionate (73.52 %) and butyrate (66.23 %) concentrations in the rectal contents of HFSD-fed mice. The results indicated that highly crystalline SC microparticles could modulate gut microbiota dysbiosis and ameliorate HFSD-induced obesity and related metabolic syndrome in mice. Furthermore, particle size might have crucial impact on the prebiotic effects of cellulose as insoluble dietary fiber.

Discrimination of cellulose microparticles in rats.

Oral perception of food particles is important in mastication and swallowing. However, the mechanism underlying particle perception remains poorly understood because of the lack of suitable experimental systems. We evaluated microparticle perception in rats utilizing insoluble cellulose particles of varying diameters (20-170 µm). The cellulose additives have polycrystalline morphologies and contain smaller crushed particles. The filtrate containing 20 µm particles at a concentration of 1.6% was passed through 3 µm pore-size filter paper, and numerous small particles equivalent to a 0.25 mM soluble solution were observed. In two-bottle preference tests, rats showed no innate preference or avoidance of particles of any size at concentrations ranging from 0.05-1.6%. Next, conditioned preference learning tests employing 8% glucose and fructose solutions were performed. After being repeatedly presented with glucose and fructose solutions containing particles of different sizes (170 and 20 µm particles or 20 µm filtrate) at a concentration of 1.6%, the rats preferred particles in glucose solution even without glucose presentation. Intriguingly, rats preferred the filtrate following repeated presentations of glucose-containing filtrate and water containing fructose. These results suggest that rats can distinguish microparticles in water. The preference learning test is useful for analyzing particle perception mechanisms in mammals.

Cellulose nanocrystals-reinforced dual crosslinked double network GelMA/hyaluronic acid injectable nanocomposite cryogels with improved mechanical properties for cartilage tissue regeneration.

Improvement of mechanical properties of injectable tissue engineering scaffolds is a current challenge. The objective of the current study is to produce a highly porous injectable scaffold with improved mechanical properties. For this aim, cellulose nanocrystals-reinforced dual crosslinked porous nanocomposite cryogels were prepared using chemically crosslinked methacrylated gelatin (GelMA) and ionically crosslinked hyaluronic acid (HA) through the cryogelation process. The resulting nanocomposites showed highly porous structures with interconnected porosity (>90%) and mean pore size in the range of 130-296 µm. The prepared nanocomposite containing 3%w/v of GelMA, 20 w/w% of HA, and 1%w/v of CNC showed the highest Young's modulus (10 kPa) and excellent reversibility after 90% compression and could regain its initial shape after injection by a 16-gauge needle in the aqueous media. The in vitro results demonstrated acceptable viability (>90%) and migration of the human chondrocyte cell line (C28/I2), and chondrogenic differentiation of human adipose stem cells. A two-month in vivo assay on a rabbit's ear model confirmed that the regeneration potential of the prepared cryogel is comparable to the natural autologous cartilage graft, suggesting it is a promising alternative for autografts in the treatment of cartilage defects.

Enhancing Chronic Wound Healing through Engineering Mg2+-Coordinated Asiatic Acid/Bacterial Cellulose Hybrid Hydrogels.

Infectious chronic wounds have gradually become a major clinical problem due to their high prevalence and poor treatment outcomes. The urgent need for wound dressings with immune modulatory, antibacterial, and angiogenic properties has led to the development of innovative solutions. Asiatic acid (AA), derived from herbs, has demonstrated excellent antibacterial, anti-inflammatory, and angiogenic effects, making it a promising candidate for incorporation into hydrogel carriers for wound healing. However, there is currently no available report on AA-based self-assembled hydrogels. Here, a novel hybrid hydrogel dressing consists of interpenetrating polymer networks composed of self-assembled magnesium ion (Mg2+) coordinated asiatic acid (AA-Mg) and bacterial cellulose (BC) is developed to promote infected chronic wound healing. A natural carrier-free self-assembled AA-Mg hydrogel with good injectable and self-healing properties could maintain the sustained release of AA and Mg2+ over an extended period. Notably, the introduction of Mg2+ boosted some pharmacological effects of self-assembled hydrogels due to its excellent anti-inflammatory and angiogenesis. In vitro studies confirmed the exceptional biocompatibility, antibacterial efficacy, and anti-inflammatory potential of the AA-Mg/BC hybrid hydrogel, which also exhibited a commendable mechanical strength. Furthermore, in vivo biological results displayed that the hybrid hydrogel significantly accelerated the wound healing process by boosting dense and organized collagen deposition and the granulation tissue and benefiting revascularization. The introduced self-assembled AA-Mg-based hydrogel offers a promising solution for the effective management of chronic wounds. This universal strategy for the preparation of self-assembled hydrogels modulated with bioactive divalent metal ions is able to excavate more herbal small molecules to construct new self-assembled biomaterials.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Bacterial cellulose as a promising material for pulmonary valve prostheses: In vivo study in a sheep model.

OBJECTIVES: Currently, no consensus exists regarding the most durable prosthesis for pulmonary valve replacement. Bacterial cellulose is a resistant, nonbiodegradable, nonpyrogenic bioimplant with low hemolysis and clotting properties. We hypothesized that bacterial cellulose heart valve prostheses could be an attractive alternative for pulmonary valve replacement. METHODS: We conducted a large animal model experiment in three adult sheep. The animals underwent open-heart surgery and cardiopulmonary bypass for bacterial cellulose conduit implantation in the pulmonary position. The sheep were followed for seven months, and clinical and laboratory parameters were analyzed. Echocardiographic evaluations were performed at 3 and 7 months. After seven months, the sheep were sacrificed and an autopsy was performed. The explanted conduits were radiologically and histopathologically analyzed. RESULTS: All sheep survived the operation, showing good recovery and normal health status; no adverse events were noted during the 7-month postoperative follow-up. Interval laboratory findings were normal with no signs of hemolysis or infection. Echocardiographic analysis after 7 months revealed a normal mean pressure gradient with excellent cusp motion and coaptation; a trace of regurgitation was found in two sheep. X-ray analysis of the explanted conduits revealed no structural defects in the leaflets with minimal calcification. Histological examination showed slight thickening of the conduit by pannus formation. No material failure, no calcification inside the material, and only minor calcification extrinsic to the matrix were observed. CONCLUSIONS: This pilot study provides evidence that bacterial cellulose may be suitable for pulmonary valve prostheses and surgical pulmonary artery plasty. Further studies on the high pressure side of the left heart are needed.

Tuning thermoresponsive properties of carboxymethyl cellulose (CMC)-agarose composite bioinks to fabricate complex 3D constructs for regenerative medicine.

3D bioprinting has emerged as a viable tool to fabricate 3D tissue constructs with high precision using various bioinks which offer instantaneous gelation, shape fidelity, and cytocompatibility. Among various bioinks, cellulose is the most abundantly available natural polymer & widely used as bioink for 3D bioprinting applications. To mitigate the demanding crosslinking needs of cellulose, it is frequently chemically modified or blended with other polymers to develop stable hydrogels. In this study, we have developed a thermoresponsive, composite bioink using carboxymethyl cellulose (CMC) and agarose in different ratios (9:1, 8:2, 7:3, 6:4, and 5:5). Among the tested combinations, the 5:5 ratio showed better gel formation at 37 °C and were further characterized for physicochemical properties. Cytocompatibility was assessed by in vitro extract cytotoxicity assay (ISO 10993-5) using skin fibroblasts cells. CMC-agarose (5:5) bioink was successfully used to fabricate complex 3D structures through extrusion bioprinting and maintained over 80 % cell viability over seven days. Finally, in vivo studies using rat full-thickness wounds showed the potential of CMC-agarose bulk and bioprinted gels in promoting skin regeneration. These results indicate the cytocompatibility and suitability of CMC-agarose bioinks for tissue engineering and 3D bioprinting applications.

Different influences of dietary fiber from various sources on the in vitro digestibility of casein as uncovered by the study of protein-dietary fiber interactions.

How different dietary fibers including pectin, cellulose and lignin affect casein digestibility was studied using in vitro static protocols. Peptides' profile, free amino acids (AAs) content, casein-DF interactions and their influences on enzymatic activities of proteolytic enzymes were studied using combined techniques. Under gastric and intestinal digestive conditions, while pectin could reduce casein digestibility (with an averaged decrease of 12.15% and 7.83, respectively) through both depletion flocculation and hydrogen-binding interactions, lignin inhibited the digestion of casein straightly through reducing the enzymatic activity of proteolytic enzymes, thereby altering the production of free AAs. Although cellulose showed the least detrimental effects, it still significantly reduced the content of Thr, Glu, Val, Leu, Phe, Lys, and no Arg was released. Deeper insight into casein-DF interactions and their influences on casein digestibility improves the development of more effective forms of DF for improving AA homeostasis in individuals.

Construction of durable antibacterial cellulose textiles through grafting dynamic disulfide-containing amino-compound and nanosilver deposition.

Cotton textile is very comfortable to wear, and also provides an ideal environment for bacterial propagation, easily causing harm to human health. In order to address this issue, various antibacterial techniques are employed for cotton finishing. However, some processes are complex and involve the use of environmentally unfriendly chemicals. In this work, a durable and efficient antibacterial cotton fabric was prepared via grafting of an amino-compound containing dynamic disulfide bonds, and then in-situ deposition of silver nanoparticles (AgNPs). Briefly, the reactive α-lipoic acid-modified polyethyleneimine (mPEI) was introduced to the cotton fibers via thiol-ene click reaction. Subsequently, the amino groups and dynamically-generated sulfhydryl groups in the mPEI molecules were used to initiate the ultrafast reduction of silver ions without the participation of additional reductant, constructing a stable antibacterial layer on fiber surface. The results reveal that the amino and thiol groups of mPEI could form coordination bonds with the deposited silver nanoparticles, and the antibacterial ability of AgNP@cotton-g-mPEI fabric remains at a high level even after 20 washing cycles. After 30 min of contact with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the antibacterial rates against both bacteria reached 99.99 %. Meanwhile, the network matrix constructed by the recombination of the dynamic disulfide bonds in mPEI endows the cotton fabric with detectable wrinkle resistance and encouraging anti-ultraviolet effect. The present work provides a novel alternative for preparation of durable and efficient antibacterial textiles.

NIR-triggered bacterial cellulose-based wound dressings for multiple synergistic therapy of infected wound.

Skin wounds are repaired by a complex series of events and overlapping phases in which bacterial infection and insufficient angiogenesis at the wound site delay the healing process. Thus, functional wound dressings with enhanced antibacterial activity and angiogenic capacity have attracted attention. Herein, bacterial cellulose (BC)-based dressings were successfully fabricated by functionalization with a polydopamine (PDA) coating and copper sulfide nanoparticles (CuS NPs). Under 808 nm laser illumination, the BC/PDA/CuS composite membranes exhibited outstanding adjustable photothermal and photodynamic activities as well as controlled Cu2+ release, endowing the composite membranes with synergetic antibacterial activity. Specially, a bactericidal efficiency of 99.7 % and 88.0 % for Staphylococcus aureus and Escherichia coli was achieved after treatment with BC/PDA/CuS5 sample under NIR irradiation (0.8 W/cm2, 10 min), respectively. Moreover, the BC/PDA/CuS5 composite membrane could enhance the angiogenesis due to the released Cu2+. In vivo experiments revealed that the BC/PDA/CuS5 composite membrane dressing could accelerate the wound closure process of the full-thickness skin defects with S. aureus by synergistically reducing inflammation, enhancing collagen deposition, and promoting vascularization under NIR irradiation. Additionally, the BC/PDA/CuS5 composite membrane exhibited high biocompatibility and biosafety. This work offers a new strategy to prepare multifunctional BC-based dressing for clinical wound healing.

Cellulose nanofibers embedded chitosan/tannin hydrogel with high antibacterial activity and hemostatic ability for drug-resistant bacterial infected wound healing.

Millions of patients annually suffer life-threatening illnesses caused by bacterial infections of skin wounds. However, the treatment of wounds infected with bacteria is a thorny issue in clinical medicine, especially with drug-resistant bacteria infections. Therefore, there is an increasing interest in developing wound dressings that can efficiently fight against drug-resistant bacterial infections and promote wound healing. In this work, an anti-drug-resistant bacterial chitosan/cellulose nanofiber/tannic acid (CS/CNF/TA) hydrogel with excellent wound management ability was developed by electrospinning and fiber breakage-recombination. The hydrogel exhibited an outstanding antibacterial property exceeding 99.9 %, even for drug-resistant bacteria. This hydrogel could adhere to the tissue surface due to its abundant catechol groups, which avoided the shedding of hydrogel during the movement. Besides, it exhibited extraordinary hemostatic ability during the bleeding phase of the wound and then regulated the wound microenvironment by absorbing water and moisturizing. Moreover, the CS/CNF/TA also promoted the regrowth of vessels and follicles, accelerating the healing of infected wound tissue, with a healing rate exceeding 95 % within a 14-day timeframe. Therefore, the CS/CNF/TA hydrogel opens a new approach for the healing of drug-resistant bacterial infected wounds.

Synthesis of bacterial cellulose nanofibers/Ag nanoparticles: Structure, characterization and antibacterial activity.

The aim of this study was to compare the characterization of bacterial cellulose nanofibers/Ag nanoparticles (BCNs/Ag nanoparticles) obtained by three different pretreatment methods of BCNs (no pretreatment, sodium hydroxide activation pretreatment and TEMPO-mediated oxidation pretreatment), which were recoded as N-BCNs/Ag nanoparticles, A-BCNs/Ag nanoparticles and O-BCNs/Ag nanoparticles, respectively. The results of scanning electron microscopy and transmission electron microscopy showed the prepared Ag nanoparticles by three different pretreatment methods were spherical and dispersed on the surface of BCNs, while the Ag nanoparticles in O-BCNs/Ag nanoparticles displayed the smallest diameter with a value of 20.25 nm and showed the most uniform dispersion on the surface of BCNs. The ICP-MS result showed O-BCNs/Ag nanoparticles had the highest content of Ag nanoparticles with a value of 2.98 wt%, followed by A-BCNs/Ag nanoparticles (1.53 wt%) and N-BCNs/Ag nanoparticles (0.84 wt%). The cytotoxicity assessment showed that the prepared BCNs/Ag nanoparticles were relatively safe. Furthermore, the O-BCNs/Ag nanoparticles had the best antioxidant and antibacterial activities as compared with the other two types of BCNs/Ag nanoparticles, where O-BCNs/Ag nanoparticles destroyed the structure of bacterial cell membranes to lead the leakage of intracellular components. This study showed that O-BCNs/Ag nanoparticles as antibacterial agents have great potential in food packaging.

Direct ink writing of biocompatible chitosan/non-isocyanate polyurethane/cellulose nanofiber hydrogels for wound-healing applications.

The demand for new biocompatible and 3D printable materials for biomedical applications is on the rise. Ideally, such materials should exhibit either biodegradability or recyclability, possess antibacterial properties, and demonstrate remarkable biocompatibility with no cytotoxic effects. In this research, we synthesized biocompatible and 3D printable hydrogels tailored for biomedical applications, such as wound healing films, by combining antibacterial double-quaternized chitosan (DQC) with cystamine-based non-isocyanate polyurethane (NIPU-Cys) - a material renowned for enhancing both the flexibility and mechanical properties of the hydrogels. To improve the rheological behavior, swelling attributes, and printability, cellulose nanofibrils were introduced into the matrix. We investigated the impact of DQC on degradability, swelling capacity, rheological behavior, printability, and cell biocompatibility. The slightly cytotoxic nature associated with quaternary chitosan was evaluated, and the optimal concentration of DQC in the hydrogel was determined to ensure biocompatibility. The resulting hydrogels were found to be suitable materials for 3D printing via a direct ink writing technique (DIW), producing porous, biocompatible hydrogels endowed with valuable attributes suitable for various wound-healing applications.

High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice.

BACKGROUND & AIMS: Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice. METHODS: Apcmin/+ mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively. RESULTS: Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apcmin/+ mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apcmin/+ mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied by increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice. CONCLUSION: High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.