Nanocrystalline Cellulose-Assisted Generation of Silver Nanoparticles for Nonenzymatic Glucose Detection and Antibacterial Agent.

Nanocrystalline cellulose (NCC) is a kind of natural biopolymers with merits of large surface area, high specific strength and unique optical properties. This report shows that NCC can serve as the substrate, allowing glucose to reduce Tollen's reagent to produce silver nanoparticles (AgNPs) at room temperature. The generation of AgNPs is affected by the factors such as the concentrations of silver ions, NCC and glucose, as well as the different reaction temperatures. The AgNPs with NCC are applied for the development of a visual, quantitative, nonenzymatic and high-sensitive assay for glucose detection in serum. This assay is also used for monitoring the concentration change of glucose in medium during cell culture. For the antibacterial activity, the minimal inhibitory concentration (MIC) of the generated AgNPs with NCC is much lower than that of commercial AgNPs, attributed to the good dispersion of AgNPs with the presence of NCC. As NCC exhibits unique advantages including green, stable, inexpensive, and abundant, the NCC-based generation of AgNPs may find promising applications in clinical diagnosis, environmental monitoring, and the control of bacteria.

A microfluidic indirect competitive immunoassay for multiple and sensitive detection of testosterone in serum and urine.

We demonstrate a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay (MIC) for multiple, sensitive, reliable and rapid detection of testosterone in human serum and urine samples. As MIC can detect biomarkers in a cost-effective and easy-to-operate manner, it may have great potential for clinical diagnosis and point-of-care testing (POCT).

Nanocrystalline Cellulose Modulates Dysregulated Intestinal Barriers in Ulcerative Colitis.

Ulcerative colitis (UC) is a recurrent chronic inflammation of the colon with increasing incidence and prevalence, which could increase the risk of colorectal cancer. It is urgent to find an effective method with few side effects. Nanocrystalline cellulose (NCC), which is from plant fibers, has a good biocompatibility and high biosafety. Herein, we used NCC to treat UC and evaluated its treatment effect by the disease activity index, intestinal pathology, inflammatory cytokines, tight junction proteins, and mucins. We studied the impact of NCC on mucin expression and gut microbiota to discuss the therapeutic mechanism. NCC can effectively treat UC by regulating the MAPK pathway of mucin 2 and the relative abundance of Akkermansia and Odoribacter, which could not cause the body damage. NCC could not cause body damage compared to the medications, while it had a better effect on the regulation of MUC2 compared to the present drug substitutes. NCC is a practical alternative for the treatment of UC.

Reductase-Labile Peptidic Supramolecular Hydrogels Aided in Oral Delivery of Probiotics.

Oral delivery of probiotics has been a promising method for treatment of inflammatory bowel diseases (IBDs). However, probiotics always suffer from substantial loss of viability due to the harsh gastrointestinal conditions, especially the highly acidic environment in the stomach and bile salts in the intestine. In addition, to overcome the challenging conditions, an ideal delivery of probiotics requires the on-demand release of probiotics upon environmental response. Herein, a novel nitroreductase (NTR) labile peptidic hydrogel based on supramolecular self-assembly is demonstrated. The efficient encapsulation of typical probiotic Escherichia coli Nissle 1917 (EcN) into supramolecular assemblies yielded a probiotic-loaded hydrogel (EcN@Gel). Such a hydrogel adequately protected EcN to improve its viability against harsh acid and bile salt environments during oral delivery. The upregulated NTR in the intestinal tract triggered the disassembly of the hydrogel and accomplished the controlled release of EcN locally. In ulcerative colitis (UC)-bearing mice, EcN@Gel showed significantly enhanced therapeutic efficacy by downregulating proinflammatory cytokines and repairing the intestinal barrier. Moreover, EcN@Gel remolded the gut microbiome by increasing the diversity and abundance of indigenous probiotics, contributing to ameliorated therapies of IBDs. The NTR-labile hydrogel provided a promising platform for the on-demand delivery of probiotics into the intestinal tract.

Bioinspired, Robust, and Absorbable Cellulose Nanofibrils/Chitosan Filament with Remarkable Cytocompatibility and Wound Healing Properties.

Surgical threads are of great importance to prevent wound infection and accelerate tissue healing in surgical treatment. Cellulose nanofibrils (CNF) and chitosan (CS) are attracting increasing attention to be employed as biomedicine materials due to their nontoxicity, cytocompatibility, and biodegradability. However, a robust and absorbable cellulose-based surgical thread has not been explored. Therefore, in this work, a bioinspired CNF/CS composite thread containing 5% cationic polyacrylamide (CPAM) by the mass of CS was prepared, and the obtained CNF/CS-5C thread exhibited excellent mechanical properties and low swelling ratio in water due to the high cross-link degree. Especially, the tensile strength (1877 ± 107 MPa) of this thread was much higher than that of most reported CNF-based threads. Meanwhile, compared with commercial silk and Vicryl surgical threads, the CNF/CS-5C thread exhibited better in vitro cytocompatibility toward endothelial and fibroblast cells and lower inflammatory response in vivo to subcutaneous tissues of rats. In addition, the obtained thread could be regarded as a promising absorbable suture, which exhibited excellent wound healing performances in vivo. Therefore, the prepared absorbable thread will open a new window to prepare novel and advanced cellulose-based threads for medical applications.

Ligand-Modified Gold Nanoparticles as Mitochondrial Modulators: Regulation of Intestinal Barrier and Therapy for Constipation.

Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.

The Antimicrobial, Hemostatic, and Anti-Adhesion Effects of a Peptide Hydrogel Constructed by the All-d-Enantiomer of Antimicrobial Peptide Jelleine-1.

Peptide hydrogels are believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and 3D printability. Most of the previously reported polypeptide hydrogels are composed of l-peptides, while the hydrogels formed by self-assembly of d-peptides are rarely reported. Herein, a peptide hydrogel constructed by D-J-1, which is the all-d-enantiomer of antimicrobial peptide Jelleine-1 (J-1) is reported. Field emission scanning electron microscope (FE-SEM) and rheologic study are performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies are carried out to evaluate its biofunction. The results show that D-J-1 hydrogel is formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π-π stacking force of aromatic ring in the structure of D-J-1. It exhibits promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibits good biocompatibility. Notably, D-J-1 hydrogel shows improved in vitro and in vivo stability when compared with its l-enantiomer J-1 hydrogel. Therefore, the present study will provide new insight into the application of d-peptide hydrogel, and provides a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use.

Synthesis of a covalent organic framework with hetero-environmental pores and its medicine co-delivery application.

The topology type and the functionalization of pores play an important role in regulating the performance of covalent organic frameworks. Herein, we designed and synthesized the covalent organic framework with hetero-environmental pores using predesigned asymmetrical dialdehyde monomer. According to the results of structural characterization, crystallinity investigation, and theoretical calculation, the hetero-environmental pores of the obtained framework are regarded as the alternant arrangement. The distinctive hetero pore structure leads the designed material to show more advantages as compared with control materials in loading both hydrophobic and hydrophilic antibiotics for wound healing. This dual-antibiotic strategy can expand the antibacterial range as compared with the single antibiotic one, and reduce the generation of drug resistance. In summary, this strategy for designing covalent organic frameworks with hetero-environmental pores can extend the structural variety and provide a pathway for improving the practical application performance of these materials.

Red blood cell membrane-functionalized Nanofibrous tubes for small-diameter vascular grafts.

The off-the-shelf small-diameter vascular grafts (SDVGs) have inferior clinical efficacy. Red blood cell membrane (Rm) has easy availability and multiple bioactive components (such as phospholipids, proteins, and glycoproteins), which can improve the clinic's availability and patency of SDVGs. Here we developed a facile approach to preparing an Rm-functionalized poly-ε-caprolactone/poly-d-lysine (Rm@PCL/PDL) tube by co-incubation and single-step rolling. The integrity, stability, and bioactivity of Rm on Rm@PCL/PDL were evaluated. The revascularization of Rm@PCL/PDL tubes was studied by implantation in the carotid artery of rabbits. Rm@PCL/PDL can be quickly prepared and showed excellent bioactivity with good hemocompatibility and great anti-inflammatory. Rm@PCL/PDL tubes as the substitute for the carotid artery of rabbits had good patency and quick remodeling within 21 days. Rm, as a "self" biomaterial with high biosafety, provides a new and facile approach to developing personalized or universal SDVGs for the clinic, which is of great significance in cardiovascular regenerative medicine and organ chip.

The interaction between nanocellulose and microorganisms for new degradable packaging: A review.

Nanocellulose (NC), including cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial cellulose (BC), has attracted a great deal of attention as a green packaging material. NC can protect food from pathogen adhesion and can be degraded by microorganisms after being discarded. In this review, we introduce preparations of NC-based film, including layer by layer (LbL) assembly, electrospinning, coating, extrusion, casting, vacuum filtration, and immersion. We summarize the interaction between microorganisms and NC, and focused on the impact of NC on microbial adhesion to surfaces and the influence of microorganisms on degradation of NC-based film. We put forward the challenges of NC faces in packaging, such as hydrophobicity, antibacterial properties, and industrialization. We finally propose future perspectives of NC-based film as the packaging material.

Nanocrystalline Cellulose Cures Constipation via Gut Microbiota Metabolism.

Constipation can seriously affect the quality of life and increase the risk of colorectal cancer. The present strategies for constipation therapy have adverse effects, such as causing irreversible intestinal damage and affecting the absorption of nutrients. Nanocrystalline cellulose (NCC), which is from natural plants, has good biocompatibility and high safety. Herein, we used NCC to treat constipation assessed by the black stool, intestinal tissue sections, and serum biomarkers. We studied the effect of NCC on gut microbiota and discussed the correlation of gut microbiota and metabolites. We evaluated the long-term biosafety of NCC. NCC could effectively treat constipation through gut microbiota metabolism, which required a small dosage and did not affect the organs and intestines. NCC could be used as an alternative to medications and dietary fiber for constipation therapy.

Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.

The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers (CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.

Development of antimicrobial oxidized cellulose film for active food packaging.

Foodborne diseases caused by bacteria have aroused ongoing concerns for food safety. Most existing packaging plastics bring pollution and potential toxicity. Here antimicrobial dialdehyde cellophane (DACP) was developed by periodate oxidation. The structure, mechanical properties, optical properties, and barrier properties of DACP were characterized. The antimicrobial activity of DACP against four Gram-positive bacteria was studied. The packaging effect of DACP for food with high water content was evaluated, including strawberry and tofu. The antimicrobial activity of DACP improved with increased aldehyde content. Compared with the polyethylene film and cellophane, our DACP exhibited excellent antimicrobial effect and extended the shelf life of food significantly, which shows promising prospects in food packaging.

Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier.

Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl L-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.

Impact of nanomaterials on the intestinal mucosal barrier and its application in treating intestinal diseases.

The intestinal mucosal barrier (IMB) is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. The dysfunction of the IMB is associated with intestinal diseases and disorders. Nanomaterials have been widely used in medicine and as drug carriers due to their large specific surface area, strong adsorbability, and good biocompatibility. In this review, we comprehensively discuss the impact of typical nanomaterials on the IMB and summarize the treatment of intestinal diseases by using nanomaterials. The effects of nanomaterials on the IMB are mainly influenced by factors such as the dosage, size, morphology, and surface functional groups of nanomaterials. There is huge potential and a broad prospect for the application of nanomaterials in regulating the IMB for achieving an optimal therapeutic effect for antibiotics, oral vaccines, drug carriers, and so on.

Advances in polysaccharide nanocrystals as pharmaceutical excipients.

Polysaccharide nanocrystals (PNs) are attractive pharmaceutical excipients due to their abundant surface hydroxyl groups, high surface charges, prominent mechanical properties, excellent fluidity, and good swelling properties. In this review, we summarize three kinds of PNs, including cellulose nanocrystals (CNCs), starch nanocrystals (SNCs), and chitin nanocrystals (ChNCs). We introduce the applications of PNs as stabilizers, adsorbents, film-forming materials, gel materials, disintegrants, and ointment matrices. We focus on the advantages of PNs to improve mechanical properties, thermal stability, therapeutic effect, biocompatibility, and release of active pharmaceutical ingredients. We discuss regulatory issues of PNs. We finally propose the challenges and future perspectives of PNs as pharmaceutical excipients.

The Effect of Different Additives on the Hydration and Gelation Properties of Composite Dental Gypsum.

Dental mold gypsum materials require fine powder, appropriate liquidity, fast curing, and easy-to-perform clinical operations. They require low linear expansion coefficient and high strength, reflecting the master model and facilitating demolding. In this article, the suitable accelerators and reinforcing agents were selected as additives to modify dental gypsum. The main experimental methods used were to compare the trends of linear expansion coefficients of several commercially available dental gypsum products over 72 h and to observe the cross-sectional microstructure of cured bodies before and after dental gypsum modification using scanning electron microscopy. By adjusting the application of additives, the linear expansion coefficient of dental gypsum decreased from 0.26% to 0.06%, while the flexural strength increased from 6.7 MPa to 7.4 MPa at 2 h. Formulated samples showed good stability and gelation properties with linear expansion completed within 12 h. It is indicated that the performance of dental gypsum materials can be improved by adding additives and nanomaterials, which provided a good reference for clinical preparation of high-precision dental prosthesis.

Adsorptivity of cationic cellulose nanocrystals for phosphate and its application in hyperphosphatemia therapy.

Nanocellulose has gained much attention because of its excellent properties. Cationic cellulose nanocrystals (cCNC) shows good adsorptivity toward negative ions and molecules. Phosphate binders are most used to treat hyperphosphatemia and it is significant to develop its alternatives with high specific and low cost in the clinic. Herein, we prepared cCNC and characterized it by FTIR, TEM, dynamic light scattering, and viscosity method. We simulated the binding process of cationic cellulose for phosphate and used it as phosphate binder for hyperphosphatemia therapy to study the phosphate binding effect and evaluate the oral toxicity. Cationic cellulose improved the conditions of mice models and efficiently decreased the level of phosphate in the serum. cCNC had a better binding effect than cationic microcrystalline cellulose both in vitro and in vivo. cCNC could be used as alternatives to phosphate binder for therapy of chronic renal failure and hyperphosphatemia.

Dialdehyde Nanocrystalline Cellulose as Antibiotic Substitutes against Multidrug-Resistant Bacteria.

Antibiotic abuse resulted in the emergence of multidrug-resistant Gram-positive pathogens, which pose a severe threat to public health. It is urgent to develop antibiotic substitutes to kill multidrug-resistant Gram-positive pathogens effectively. Herein, the antibacterial dialdehyde nanocrystalline cellulose (DNC) was prepared and characterized. The antibacterial activity and biosafety of DNC were studied. With the increasing content of aldehyde groups, DNC exhibited high antibacterial activity against Gram-positive pathogens in vitro. DNC3 significantly reduced the amounts of methicillin-resistant Staphylococcus aureus (MRSA) on the skin of infected mice models, which showed low cytotoxicity, excellent skin compatibility, and no acute oral toxicity. DNC exhibited potentials as antibiotic substitutes to fight against multidrug-resistant bacteria, such as ingredients in salves to treat skin infection and other on-skin applications.

Anticoagulant Hydrogel Tubes with Poly(ɛ-Caprolactone) Sheaths for Small-Diameter Vascular Grafts.

Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.