Discovery of a highly selective fluorescent probe for hydrogen peroxide and its biocompatibility evaluation and bioimaging applications in cells and zebrafish.

As one of the most widely distributed reactive oxygen species in vivo, hydrogen peroxide plays divergent and important roles in cell growth, differentiation and aging. When the level of hydrogen peroxide in the body is abnormal, it will lead to genome mutation and induce irreversible oxidative modification of proteins, lipids and polysaccharides, resulting in cell death or even disease. Therefore, it is significant to develop a sensitive and specific probe for real-time detection of hydrogen peroxide in vivo. In this study, the response mechanism between hydrogen peroxide and probe QH was investigated by means of HRMS and the probe showed good optical properties and high selectivity to hydrogen peroxide. Note that the evaluating of probe biocompatibility resulted from cytotoxicity test, behavioral test, hepatotoxicity test, cardiotoxicity test, blood vessel toxicity test, immunotoxicity test and neurotoxicity test using cell and transgenic zebrafish models with more than 20 toxic indices. Furthermore, the detection performance of the probe for hydrogen peroxide was evaluated by multiple biological models and the probe was proved to be much essential for the monitoring of hydrogen peroxide in vivo.

Atomic-scale observation of non-classical nucleation-mediated phase transformation in a titanium alloy.

Two-phase titanium-based alloys are widely used in aerospace and biomedical applications, and they are obtained through phase transformations between a low-temperature hexagonal closed-packed α-phase and a high-temperature body-centred cubic ß-phase. Understanding how a new phase evolves from its parent phase is critical to controlling the transforming microstructures and thus material properties. Here, we report time-resolved experimental evidence, at sub-ångström resolution, of a non-classically nucleated metastable phase that bridges the α-phase and the ß-phase, in a technologically important titanium-molybdenum alloy. We observed a nanosized and chemically ordered superstructure in the α-phase matrix; its composition, chemical order and crystal structure are all found to be different from both the parent and the product phases, but instigating a vanishingly low energy barrier for the transformation into the ß-phase. This latter phase transition can proceed instantly via vibrational switching when the molybdenum concentration in the superstructure exceeds a critical value. We expect that such a non-classical phase evolution mechanism is much more common than previously believed for solid-state transformations.

Emerging Advancements in Piezoelectric Nanomaterials for Dynamic Tumor Therapy.

Cancer is one of the deadliest diseases, having spurred researchers to explore effective therapeutic strategies for several centuries. Although efficacious, conventional chemotherapy usually introduces various side effects, such as cytotoxicity or multi-drug resistance. In recent decades, nanomaterials, possessing unique physical and chemical properties, have been used for the treatment of a wide range of cancers. Dynamic therapies, which can kill target cells using reactive oxygen species (ROS), are promising for tumor treatment, as they overcome the drawbacks of chemotherapy methods. Piezoelectric nanomaterials, featuring a unique property to convert ultrasound vibration energy into electrical energy, have also attracted increasing attention in biomedical research, as the piezoelectric effect can drive chemical reactions to generate ROS, leading to the newly emerging technique of ultrasound-driven tumor therapy. Piezoelectric materials are expected to bring a better solution for efficient and safe cancer treatment, as well as patient pain relief. In this review article, we highlight the most recent achievements of piezoelectric biomaterials for tumor therapy, including the mechanism of piezoelectric catalysis, conventional piezoelectric materials, modified piezoelectric materials and multifunctional piezoelectric materials for tumor treatment.

Does mandibular advancement with clear aligners have the same skeletal and dentoalveolar effects as traditional functional appliances?

BACKGROUND: The study aimed to compare the dentoskeletal effects of Vanbeek Activator, Herbst, Twin-Block and Mandibular Advancement with clear aligners in children with skeletal Class II malocclusions. METHODS: A sample with sixty-three patients (37 males, 26 females) was included and divided into untreated control group (C, n = 12), Vanbeek Activator group (V, n = 14), Herbst group (H, n = 11), Twin-Block group (TB, n = 12) and MA group (MA, n = 14). Cephalometric analysis and Johnston Pitchfork analysis were performed to quantify the skeletal and dentoalveolar components in molar relationship and overjet correction. Compare the differences of cephalometric data and Johnston-analysis data. RESULTS: The treatment changes showed significant differences in SNB, FH-NP, NA-PA, Co-Go, Co-Pog, ANB, lower facial height ratio, U1-PP, U6-PP, L1-MP and U1-L1. All the appliances improved overjet relationships significantly (Vanbeek, Herbst, Twin-Block and MA were 2.77 mm, 5.53 mm, 4.73 mm and 3.66 mm respectively) with significant retraction of maxillary incisors. The lower incisor displacement of group V and MA was negative, while that of group H and TB was positive and there were significant differences. Molar relationships were also improved by 3.45 mm, 6.85 mm, 3.48 mm and 0.92 mm for Vanbeek, Herbst, Twin-Block and MA. Mandible displacement showed a trend of group H > TB > V > MA. The displacement of maxillary molars in group H was greater than that in group C, TB and MA, and that of mandibular ones was greater than that in group C, V and MA, significantly. Herbst, Twin-Block and MA have more significant dentoalveolar effect than Vanbeek, while Vanbeek has more skeletal effect than the others especially in restraining maxillary growth. CONCLUSIONS: Four appliances are all effective in mandibular advancement, modification of class II molar relationship and deep overjet, with unavoidable increase in lower facial ratio. Vanbeek Activator has the most skeletal effects. Vanbeek and MA have a good control of mandibular incisors while more compensatory lower incisors proclination in Herbst and Twin-Block. Herbst has greater maxillary molar distalization. MA allows aligning and leveling meanwhile leading the mandible forward.

Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Synergy between plant phenols and carotenoids in stabilizing lipid-bilayer membranes of giant unilamellar vesicles against oxidative destruction.

We have investigated the synergism between plant phenols and carotenoids in protecting the phosphatidylcholine (PC) membranes of giant unilamellar vesicles (GUVs) from oxidative destruction, for which chlorophyll-a (Chl-a) was used as a lipophilic photosensitizer. The effect was examined for seven different combinations of ß-carotene (ß-CAR) and plant phenols. The light-induced change in GUV morphology was monitored via conventional optical microscopy, and quantified by a dimensionless image-entropy parameter, ΔE. The ΔE-t time evolution profiles exhibiting successive lag phase, budding phase and ending phase could be accounted for by a Boltzmann model function. The length of the lag phase (LP in s) for the combination of syringic acid and ß-CAR was more than seven fold longer than for ß-CAR alone, and those for other different combinations followed the order: salicylic acid < vanillic acid < syringic acid > rutin > caffeic acid > quercetin > catechin, indicating that moderately reducing phenols appeared to be the most efficient membrane co-stabilizers. The same order held for the residual contents of ß-CAR in membranes after light-induced oxidative degradation as determined by resonance Raman spectroscopy. The dependence of LP on the reducing power of phenols coincided with the Marcus theory plot for the rate of electron transfer from phenols to the radical cation ß-CAR˙+ as a primary oxidative product, suggesting that the plant phenol regeneration of ß-CAR plays an important role in stabilizing the GUV membranes, as further supported by the involvement of CAR˙+ and the distinct shortening of its lifetime as shown by transient absorption spectroscopy.

Polystyrene Encapsulated SERS Tags as Promising Standard Tools: Simple and Universal in Synthesis; Highly Sensitive and Ultrastable for Bioimaging.

Surface coating determined the sensitivity and stability of surface-enhanced Raman scattering (SERS) tags in bioanalysis. The reported various coatings suffered from the drawbacks of a lack of rigidity, stability, or synthesis versatility. Herein, we demonstrated robust polystyrene (PS) coated SERS tags that could be prepared by an easy and universal approach. Taking advantages of biocompatible, transparent, compact properties of PS shell, the coated tags showed satisfactory sensitivity, biocompatibility, and superior structural stability in cell and in vivo imaging applications. More importantly, the PS coating strategy allowed for the encapsulation of SERS tags encoded with not only thiolated but also nonthiolated Raman reporters without loss of sensitivity, as exemplified in the synthesis of 9 different resonant dye-encoded tags. Moreover, the coating of SERS tags with various kinds of substrates was achieved via the same standard protocol. Comparing with widespread silica coated tags, the PS coated ones were more stable in harsh conditions and had an easily expanded ultrasensitive (resonant) tags library with much lower cost (no need of expensive sulfhydryl/isothiocyano reporters with limited types), illustrating great promise as standard analytical tools of commercialized value for bioanalysis, medical diagnostics, and environmental science studies.

Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA.

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100-280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.

Reversible Bacterial Adhesion on Mixed Poly(dimethylaminoethyl methacrylate)/Poly(acrylamidophenyl boronic acid) Brush Surfaces.

A simple and versatile method for the preparation of surfaces to control bacterial adhesion is described. Substrates were first treated with two catechol-based polymerization initiators, one for thermal initiation and one for visible-light photoinitiation. Graft polymerization in sequence of dimethylaminoethyl methacrylate (DMAEMA) and 3-acrylamidebenzene boronic acid (BA) from the surface-bound initiators to form mixed polymer brushes on the substrate was then carried out. The PDMAEMA grafts were thermally initiated and the PBA grafts were visible-light-photoinitiated. Gold, poly(vinyl chloride) (PVC), and poly(dimethylsiloxane) (PDMS) were used as model substrates. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), and ellipsometry analysis confirmed the successful grafting of PDMAEMA/PBA mixed brushes. We demonstrated that the resulting surfaces showed charge-reversal properties in response to change of pH. The transition in surface charge at a specific pH allowed the surface to be reversibly switched from bacteria-adhesive to bacteria-resistant. At pH 4.5, below the isoelectric points (IEP, pH 5.3) of the mixed brushes, the surfaces are positively charged and the negatively charged Gram-positive S. aureus adheres at high density (2.6 × 10(6) cells/cm(2)) due to attractive electrostatic interactions. Subsequently, upon increasing the pH to 9.0 to give negatively charged polymer brush surface, ∼90% of the adherent bacteria are released from the surface, presumably due to repulsive electrostatic interactions. This approach provides a simple method for the preparation of surfaces on which bacterial adhesion can be controlled and is applicable to a wide variety of substrates.

Extracellular Matrix Remodelling of the Periodontium under Orthodontic Force.

As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.

Plasmonic filter paper for preconcentration, separation and SERS detection harmful chemicals in chili product by fluid flow.

We proposed a triple functional SERS substrate by immobilized Ag nanoparticles on the surface of filter paper. The high dense Ag nanoparticles were distributed on the SERS substrate via in-situ growth process. By optimizing the parameter in preparation process, the optimal filter paper SERS substrate was fabricated by using 30 mM of AgNO3 with 20 S growth time. Due to capillary-effect wicking of cellulose fiber, the paper SERS substrate provide simple, fast and pump-free function for transferring analyte onto sharp tip through development of fluid. The fluid flow also brings target concentrate effect within the tip area. Furthermore, the separation feasibility was obtained during the development process of fluid. The preconcentrated effects not only enhanced the SERS signal of analyte, but also improve the fluorescence visible effect. The filter paper SERS substrate was successfully used for separating, concentrating and detecting Sudan dye from chili product, the detection limit could achieve 10-6 M. This study developed a portable, cost-effective and eco-friendly SERS substrate for separating and detecting trace chemical in food.

Multifunctional coatings based on candle soot with photothermal bactericidal property and desired biofunctionality.

Functional coatings with desired bioactivities are required for various biomedical applications. Candle soot (CS) composed of carbon nanoparticles has attracted significant attention as a versatile component of functional coatings because of its unique physical and structural characteristics. However, the application of CS-based coatings in the biomedical field is still limited due to the lack of modification methods that can endow them with specific biofunctionality. Herein, a facile and widely applicable approach to fabricate multifunctional CS-based coatings is developed by grafting functional polymer brushes on the silica-stabilized CS. The resulting coatings not only exhibited excellent near-infrared-activated biocidal ability (the killing efficiency was over 99.99 %) due to the inherent photothermal property of CS but also showed desired biofunctions (such as antifouling property or controllable bioadhesion; the repelling efficiency and bacterial release ratio were nearly 90 %) originated from the grafted polymers. Moreover, these biofunctions were enhanced by the nanoscale structure of CS. Because the deposition of CS is a simple substrate-independent process while the grafting of polymer brushes via surface-initiated polymerization is applicable to a wide range of vinyl monomers, the proposed approach can be potentially used for the fabrication of multifunctional coatings and would extend the applications of CS in the biomedical field.

Injectable Decellularized Extracellular Matrix Hydrogel Containing Stromal Cell-Derived Factor 1 Promotes Transplanted Cardiomyocyte Engraftment and Functional Regeneration after Myocardial Infarction.

Transplantation of exogenous cardiomyocytes (CMs) is a hopeful method to treat myocardial infarction (MI). However, its clinical application still remains challenging due to low retention and survival rates of the transplanted cells. Herein, a stromal cell-derived factor 1 (SDF-1)-loaded injectable hydrogel based on a decellularized porcine extracellular matrix (dECM) is developed to encapsulate and deliver CMs locally to the infarct area of the heart. The soluble porcine cardiac dECM is composed of similar components such as the human cardiac ECM, which could be self-assembled into a nanofibrous hydrogel at physiological temperature to improve the retention of transplanted CMs. Furthermore, the chemokine SDF-1 could recruit endogenous cells to promote angiogenesis, mitigating the ischemic microenvironment and improving the survival of CMs. The results in vitro show that this composite hydrogel exhibits good biocompatibility, anti-apoptosis property, and chemotactic effects for mesenchymal stromal cells and endothelial cells through SDF-1-CXCR4 axis. Moreover, intramyocardial injection of this composite hydrogel to the infarcted area leads to the promotion of angiogenesis and inhibition of fibrosis, reducing the infarction size and improving the cardiac function. The combination of natural biomaterials, exogenous cells, and bioactive factors shows potential for MI treatment in the clinical application.

Effect of Premolar Extraction on the Upper Airway in Adult and Adolescent Orthodontic Patients: a Meta-analysis.

OBJECTIVE: To analyse the effects of premolar extraction on the upper airway in adult and adolescent orthodontic patients using CBCT. METHODS: The Embase, Web of Science, Cochrane Library and Medline (via PubMed) databases were searched with no language restrictions. Longitudinal studies in which CBCT was applied to assess the effects of tooth extraction on the upper airway were included in the analysis. Two authors performed the study selection, methodological quality assessment, data extraction and data synthesis independently. RESULTS: A total of 12 studies were included, six of which were eligible for quantitative synthesis. In the adult group, the nasopharynx and oropharynx volume showed no significant change, and the minimum cross-sectional area of the upper airway demonstrated a non-significant decrease compared to the non-extraction group. In the adolescent group, the nasopharynx volume, oropharynx volume and minimum cross-sectional area of the upper airway increased in a non-significant manner. CONCLUSION: The currently available evidence indicates that tooth extraction does not increase the risk of airway collapse in adult and adolescent patients. The present findings should be interpreted with caution and evaluated in further high-quality studies.

A Photothermal Nanoplatform with Sugar-Triggered Cleaning Ability for High-Efficiency Intracellular Delivery.

Intracellular delivery of functional molecules is of great importance in various biomedical and biotechnology applications. Recently, nanoparticle-based photothermal poration has attracted increasing attention because it provided a facile and efficient method to permeabilize cells transiently, facilitating the entry of exogenous molecules into cells. However, this method still has some safety concerns associated with the nanoparticles that bind to the cell membranes or enter the cells. Herein, a nanoplatform with both photothermal property and sugar-triggered cleaning ability for intracellular delivery is developed based on phenylboronic acid (PBA) functionalized porous magnetic nanoparticles (named as M-PBA). The M-PBA particles could bind to the target cells effectively through the specific interactions between PBA groups and the cis-diol containing components on the cell membrane. During a short-term near-infrared irradiation, the bound particles convert absorbed light energy to heat, enabling high-efficiency delivery of various exogenous molecules into the target cells via a photothermal poration mechanism. After delivery, the bound particles could be easily "cleaned" from the cell surface via mild sugar-treatment and collected by a magnet, avoiding the possible side effects caused by the entrance of particles or their fragments. The delivery and cleaning process is short and effective without compromising the viability and proliferation ability of the cells with delivered molecules, suggesting that the M-PBA particles could be used as promising intracellular delivery agents with a unique combination of efficiency, safety, and flexibility.

A novel FAM83H variant causes familial amelogenesis imperfecta with incomplete penetrance.

BACKGROUND: Amelogenesis imperfecta (AI) is known to be a monogenic genetic disease caused by a variety of genes demonstrating a wide spectrum of penetrance. FAM83H is reported to be involved in AI: however, whether FAM83H causes AI with incomplete penetrance is unclear. METHODS: Whole-exome sequencing was performed on two patients with AI, and putative disease-related variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed to functionally characterize the identified disease-causing variants. RESULTS: We identified a novel heterozygous nonsense variant of FAM83H (NM_198488: c.1975G > T, p.Glu659Ter); in vitro functional analysis showed that this mutant produced mislocalized proteins and was deleterious. Surprisingly, the clinical manifestations of each of the six individuals carrying this variant were different, with one carrier appearing to be completely asymptomatic for AI. CONCLUSION: Our findings expand the variant spectrum for FAM83H and the phenotypic spectrum for FAM83H-associated AI and suggest that FAM83H-mediated AI exhibits incomplete penetrance.

Lipid droplet-hitchhiking probe creates Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques.

Since atherosclerosis, a disease characterized by abnormal arterial lipid deposition, may lead to fatal cardiovascular diseases, imaging of atherosclerotic plaques is of great value for their pathological assessment. In this study, we propose a lipid droplet (LD)-hitchhiking strategy to in situ create Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques via homologous targeting effect. In our design, functional liposomes (DCP liposomes) composed of phospholipid dioleoylphosphatidylserine (DOPS), a novel LD inducer we found, and Cypate-PC, a synthesized lipid-like molecular probe, have demonstrated great capability of inducing LDs in monocytes/macrophages while being enveloped into the resulting Trojan foam cells. Taking advantage of homologous targeting effect, the imaging probe hitchhikes on the LDs in Trojan foam cells for targeted transport to the plaque sites. Moreover, the confinement in highly hydrophobic LDs endows the imaging probe with high efficiency in light absorption, enabling greatly intensified fluorescence/photoacoustic signals. The DCP liposomes have shown great potency in inducing the generation of Trojan foam cells, and eventually ex vivo fluorescence imaging and in vivo photoacoustic imaging of atherosclerotic plaques. The proposed strategy provides more insights into the design of targeted imaging methodologies, and also an effective avenue to facilitate the evaluation and subsequent treatment of atherosclerotic plaques.

Cross-linked poly(trimethylene carbonate-co-L-lactide) as a biodegradable, elastomeric scaffold for vascular engineering applications.

A series of copolymers of trimethylene carbonate (TMC) and L-lactide (LLA) were synthesized and evaluated as scaffolds for the production of artificial blood vessels. The polymers were end-functionalized with acrylate, cast into films, and cross-linked using UV light. The mechanical, degradation, and biocompatibility properties were evaluated. High TMC polymers showed mechanical properties comparable to human arteries (Young's moduli of 1.2-1.8 MPa and high elasticity with repeated cycling at 10% strain). Over 84 days degradation in PBS, the modulus and material strength decreased gradually. The polymers were nontoxic and showed good cell adhesion and proliferation over 7 days using human mesenchymal stem cells. When implanted into the rat peritoneal cavity, the polymers elicited formation of tissue capsules composed of myofibroblasts, resembling immature vascular smooth muscle cells. Thus, these polymers showed properties which were tunable and favorable for vascular tissue engineering, specifically, the growth of artificial blood vessels in vivo.

Universal Antifouling and Photothermal Antibacterial Surfaces Based on Multifunctional Metal-Phenolic Networks for Prevention of Biofilm Formation.

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.

Dual-Functional Surfaces Based on an Antifouling Polymer and a Natural Antibiofilm Molecule: Prevention of Biofilm Formation without Using Biocides.

Pathogenic biofilms formed on the surfaces of implantable medical devices and materials pose an urgent global healthcare problem. Although conventional antibacterial surfaces based on bacteria-repelling or bacteria-killing strategies can delay biofilm formation to some extent, they usually fail in long-term applications, and it remains challenging to eradicate recalcitrant biofilms once they are established and mature. From the viewpoint of microbiology, a promising strategy may be to target the middle stage of biofilm formation including the main biological processes involved in biofilm development. In this work, a dual-functional antibiofilm surface is developed based on copolymer brushes of 2-hydroxyethyl methacrylate (HEMA) and 3-(acrylamido)phenylboronic acid (APBA), with quercetin (Qe, a natural antibiofilm molecule) incorporated via acid-responsive boronate ester bonds. Due to the antifouling properties of the hydrophilic poly(HEMA) component, the resulting surface is able to suppress bacterial adhesion and aggregation in the early stages of contact. A few bacteria are eventually able to break through the protection of the anti-adhesion layer leading to bacterial colonization. In response to the resulting decrease in the pH of the microenvironment, the surface could then release Qe to interfere with the microbiological processes related to biofilm formation. Compared to bactericidal and anti-adhesive surfaces, this dual-functional surface showed significantly improved antibiofilm performance to prevent biofilm formation involving both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus for up to 3 days. In addition, both the copolymer and Qe are negligibly cytotoxic, thereby avoiding possible harmful effects on adjacent normal cells and the risk of bacterial resistance. This dual-functional design approach addresses the different stages of biofilm formation, and (in accordance with the growth process of the biofilm) allows sequential activation of the functions without compromising the viability of adjacent normal cells. A simple and reliable solution may thus be provided to the problems associated with biofilms on surfaces in various biomedical applications.