Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.

B16F10 Cell Membrane-Based Nanovesicles for Melanoma Therapy Are Superior to Hyaluronic Acid-Modified Nanocarriers.

Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference (p > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.

On-nylon membrane detection of nucleic acid molecules by rolling circle amplification.

Positively-charged nylon membrane (NM) is a general solid-phase support for nucleic acid detection due to its convenient immobilization of nucleic acid materials by direct electrostatic adherence and simple UV crosslinking. Rolling circle amplification (RCA) is a widely used isothermal DNA amplification technique for nucleic acid detection. Near-infrared fluorescence (NIRF) is a new fluorescence technique with high sensitivity due to low background. This study developed a simple method for detecting nucleic acid molecules by combining the advantages of NM, RCA and NIRF, named NIRF-based solid phase RCA on nylon membrane (NM-NIRF-sRCA). The detection system of this method only need two kinds of nucleic acid molecules: target-specific probes with a RCA primer (P) at their 3' end and a rolling circle (RC). The detection procedure consists of four steps: (1) immobilizing detected nucleic acids on NM by UV crosslinking; (2) hybridizing NM with specific probes and RC; (3) amplifying by a RCA reaction containing biotin-dUTP; (4) incubating NM with NIRF-labeled streptavidin and imaging with a NIRF imager. The method was fully testified by detecting oligonucleotides, L1 fragments of various HPV subtypes cloned in plasmid, and E.coli genomic DNA. This study thus provides a new facile method for detecting nucleic acid molecules.

Study on the Effects of Orthodontics on Anterior Tooth Displacement in Patients.

Objective: The purpose of this study was to investigate the therapeutic effect of orthodontic treatment on anterior tooth displacement caused by periodontal disease. Methods: A prospective study was performed in 86 patients with anterior tooth displacement caused by periodontal disease. These patients were divided into the experimental group and the control group according to the intervention methods. For the control group, patients were treated with conventional therapy. The experimental group used straight wire orthodontic technique for orthodontic treatment on the basis of conventional treatment. Comparisons were performed between two groups in term of bleeding index, alveolar bone height, anterior tooth coverage, periodontal pocket depth, probing depth, clinical crown length, tooth root length, inflammatory cytokines levels, and orthodontic satisfaction. Results: Comparison of bleeding index, alveolar bone height, anterior tooth coverage, periodontal pocket depth, probing depth, clinical crown length, tooth root length, and inflammatory cytokines levels between two groups before treatment indicated that there were no statistical differences (all P > 0.05). After treatment, bleeding index, alveolar bone height, anterior tooth coverage, periodontal pocket depth, probing depth, clinical crown length, and serum levels of IL-6 and TNF-α in the experimental group were lower than those in the control group (all P < 0.05), while the serum level of IL-2 in the experimental group was more than that in the control group (P < 0.05). Also, there was no difference for tooth root length between two groups. Moreover, compared with the control group, orthodontic satisfaction in the experimental group was significantly increased. Conclusion: The efficacy of orthodontic treatment in patients with anterior tooth displacement caused by periodontal disease is higher than that of only using conventional therapy, as it helps improve their periodontal health, alveolar bone height, clinical crown length, inflammatory factor levels, and orthodontic satisfaction of patients.

Carboxymethyl chitosan-decorated proliposomes as carriers for improved stability and sustained release of flaxseed oil.

A flaxseed oil carboxymethyl chitosan-decorated proliposome system was fabricated in this research. The physicochemical characteristics, stability, and in vitro release behaviors of flaxseed oil were studied and compared with that of flaxseed oil-loaded liposomes. The results of dynamic light scattering, transmission electron microscopy, and oxidation stability indicated that the storage stability of proliposomes was better. After 28 days of storage, the peroxide value of flaxseed oil-loaded liposomes (20.1 meq/kg) was significantly (P < 0.05) higher than that of flaxseed oil-loaded proliposomes (9.0 meq/kg); the thiobarbituric acid reactive substances in the former (0.53 mmol/kg) was also higher than that in the latter (0.27 mmol/kg). The in vitro release behavior of flaxseed oil indicated the proliposomes were more stable in the simulated gastrointestinal fluids. Therefore, the flaxseed oil-loaded proliposome system could be a promising vehicle for delivery flaxseed oil in food industry. PRACTICAL APPLICATION: A flaxseed oil-loaded proliposome delivery system was fabricated in this research. Their physical and oxidation stability of flaxseed oil were improved, and the in vitro cumulative release of flaxseed oil was delayed compared with flaxseed oil liposomes. This system may provide an effective strategy for the flaxseed oil encapsulation in the food industry.

Biodegradable hybrid mesoporous silica nanoparticles for gene/chemo-synergetic therapy of breast cancer.

Mesoporous silica nanoparticles have been extensively explored in anticancer nanomedicine due to their excellent biodegradability, which is one important focus in their further clinical translations. However, the traditional design concepts based on the functional modification with active groups cannot significantly improve the controlled drug release efficiency and anticancer effect. Herein, a molecularly organic-inorganic hybrid mesoporous silica nanoparticle (HMSN) nanocarrier coated with hyaluronic acid (HA) and polyethyleneimine (PEI) was constructed for the gene/chemo-synergetic therapy of breast cancer. Notably, HMSN with tumor-sensitive disulfide bond and targeting ligand HA can be decomposed when it encounters high concentration of glutathione (GSH) and hyaluronidase (HAase). The biodegradability of host molecules and the fast disintegration of the framework in tumor microenvironment can also accelerate the stimuli responsive release of cargos inside the pore space. Furthermore, the grafting of polyethyleneimine (PEI) could increase gene loading efficiency. From the above, the smart approach involves a combination of biodegradability and biological effect and results in synergetic antitumor effect of gene and chemical drug on breast cancer. All these findings demonstrated that HMSN/HA/PEI nanocarriers can be suitable for biomedical application, paving the way to fast development of multi-functional nano-biomedicine.

Evaluation of a bioactive bone-inducing material consisting of collagen scaffolds and collagen-binding bone morphogenetic protein 2.

Bioactive bone-inducing material (BBIM) is a collagen-based scaffold composed of demineralized bone matrix and collagen-binding domain bone morphogenetic protein 2 (BMP-2). BBIM is regarded as a promising bone-inducing scaffold to repair bone defects. In this work, we evaluated the biocompatibility and osteogenecity of BBIM. Using enzyme-linked immunosorbent assay, the level of BMP-2 on BBIM was detected and considered adequate. Kunming mice were used as the animal model to investigate the acute systemic toxicity, long-term bone regeneration, ectopic bone formation, and chronic systemic toxicity. Results show that BBIM induced no serious inflammatory reaction or acute and chronic systemic toxicity. Our analyses also demonstrated significant homogeneous ectopic bone formation as well as significantly high numbers of erythrocytes in the BBIM groups in the chronic systemic toxicity study, a phenomenon which may provide indirect proof of the bone regeneration capacity of BBIM, which may be considered as a bioactivity indicator in future studies.

Selective and sensitive determination of uric acid in the presence of ascorbic acid and dopamine by PDDA functionalized graphene/graphite composite electrode.

In this work, a facile electrochemical sensor based on poly(diallyldimethylammonium chloride) (PDDA) functionalized graphene (PDDA-G) and graphite was fabricated. The composite electrode exhibited excellent selectivity and sensitivity towards uric acid (UA), owing to the electrocatalytic effect of graphene nanosheets and the electrostatic attractions between PDDA-G and UA. The anodic peak current of UA obtained by cyclic voltammetry (CV) increased over 10-fold compared with bare carbon paste electrode (CPE). And the reversibility of the oxidation process was improved significantly. Differential pulse voltammetry (DPV) was used to determine UA in the presence of ascorbic acid (AA) and dopamine (DA). It was found that all of oxidation peaks of three species could be well resolved, and the peak current of UA was much stronger than the other two components. More importantly, considerable-amount of AA and DA showed negligible interference to UA assay. The calibration curve for UA ranged from 0.5 to 20 µmol L(-1) with a correlation coefficient of 0.9934. The constructed sensor has been employed to quantitatively determine UA in urine samples.

CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac troponin I for acute myocardial infarction diagnosis.

A label-free biosensor for electrical detection of cardiac troponin I (cTnI), a highly sensitive and selective biomarker of acute myocardial infarction (AMI), is demonstrated using silicon nanowire (SiNW) based field-effect transistors (FETs). The FET devices were fabricated by a complementary metal oxide semiconductor (CMOS) compatible top-down approach to define the SiNW followed by tetramethylammonium hydroxide (TMAH) wet etching. Electrical characterizations of the SiNW FET revealed an ambipolar conduction characteristic with an on/off ratio of 10(5)-10(6). CTnI monoclonal antibodies were then covalently immobilized on the SiNW surfaces. By integrating with a homemade biosensor measurement system, the biosensor exhibited rapid and sensitive response to cTnI proteins. The current response showed a nature of logarithm relationship against the cTnI concentration from 46 ng/mL down to 0.092 ng/mL. Moreover, an anti-interference capability of the fabricated biosensor was also assessed. By utilizing the top-down fabrication method, this work provides an efficient way for the cTnI proteins detection with an enormous potential of mass-production, which definitely facilitate the practical applications.

Preparation and characterization of novel crown ether functionalized ionic liquid-based solid-phase microextraction coatings by sol-gel technology.

A novel crown ether functionalized ionic liquid (IL), 1-allyl-3-(6'-oxo-benzo-15-crown-5 hexyl) imidazolium hexafluorophosphate was synthesized and used as selective stationary phase to prepare task-specific IL-based solid phase microextraction (SPME) fibers by sol-gel method and free radical cross-linking technology. The underlying mechanism of the sol-gel reaction was proposed and the successful chemical bonding of the crown ether functionalized IL to the formed hybrid organic-inorganic copolymer coating was confirmed by FT-IR spectroscopy. The performance of this in situ created crown ether functionalized IL-based SPME fibers, was investigated in detail. The coating has porous surface structure, stable performance in high temperature (to 340 °C) and in different solutions (water, organic solvent, acid and alkali), and good coating preparation reproducibility. In contrast to the sol-gel derived 1-allyl-3-methyl imidazolium hexafluorophosphate-based coating prepared in our previous work with the identical procedure, the extraction performance of this newly developed sol-gel crown ether functionalized IL-based coating was superior for alcohols, phthalate esters, phenolic environmental estrogens, fatty acids and aromatic amines due to the introduction of benzo-15-crown-5 functional group in IL structure. Moreover, it was shown to provide higher or comparable extraction efficiencies for most analytes studied than did the commercial PDMS, PDMS/DVB and PA fibers.