Showing papers in "Journal of Materials Chemistry B in 2015"

Fundamentals of double network hydrogels

Abstract: Double network (DN) hydrogels as promising soft-and-tough materials intrinsically possess extraordinary mechanical strength and toughness due to their unique contrasting network structures, strong interpenetrating network entanglement, and efficient energy dissipation. It has been ∼11 years since the first PAMPS–PAAm DN hydrogel was developed, but the research and development of new DN hydrogels are still at a very early stage. A vast number of network monomers available in the current chemical inventory provide the possibility to design new DN gels and to explore the fundamental relationship of DN gels among network structures, mechanical properties, and toughening mechanisms, which help to derive new design principles for the next-generation tough hydrogels. In this review, we strive to highlight the development and fundamentals of DN gels covering from preparation methods, network structures, to toughening mechanisms over the last decade.

Non-toxic, non-biocide-release antifouling coatings based on molecular structure design for marine applications

Abstract: Marine biofouling generally refers to the undesirable accumulation of biological organisms on surfaces in contact with seawater. This natural phenomenon represents a major economic concern for marine industries, e.g. for ships and vessels, oil and wind-turbine sea-platforms, pipelines, water valves and filters, as it limits the performance of devices, materials and underwater structures and increases the costs related to transport delays, hull maintenance and repair, cleaning and desalination units, corrosion and structure break-down. In the last few decades, many efforts have been spent into developing efficient antifouling (AF) surfaces (coatings) combining advances in materials science and recent knowledge of marine chemistry and biology. However, the extensive use of toxic and harmful compounds in the formulations raised increasing health and environmental concerns leading to stricter regulations which pushed marine industries to search for new AF strategies. This review presents the recent research progress made in green strategies for AF coatings using non-toxic, non-biocide-release based principles for marine applications. The two main approaches, detachment of biofoulants or preventing biofoulants attachment, are reviewed in detail and new promising routes based on amphiphilic, (super)hydrophilic, and topographic (structured) surfaces are highlighted. The chemical and physical aspects of the AF mechanisms behind the AF strategies reviewed are emphasized, with special attention to the early stages of biofoulant adhesion, keeping the focus on the materials' molecular structure and properties which allow obtaining the final desired antifouling behaviour.

An overview of the suitability of hydrogel-forming polymers for extrusion-based 3D-printing

Abstract: This review evaluates hydrogel-forming polymers that are suitable for soft tissue engineering with a focus on materials that can be fabricated using additive manufacturing (3D-printing). An overview of the specific material requirements for hydrogel-based tissue engineering constructs is presented. This is followed by an explanation of the various hydrogel-forming polymer classes that includes a detailed examination of material properties that are critical for extrusion printing. Specifically, mechanisms for hydrogel formation, degradation, and biological response, activity and compatibility are explored. A discussion of extrusion printing strategies for printable hydrogel-forming polymers is then presented in conjunction with a list of considerations to guide future tissue engineering developments.

Self-polymerization of dopamine and polyethyleneimine: novel fluorescent organic nanoprobes for biological imaging applications

Abstract: The development of novel fluorescent nanoprobes has attracted great current research interest over the past few decades due to their superior optical properties and multifunctional capability as compared with small organic dyes. Although great advance has been made in the utilization of fluorescent nanoprobes for biomedical applications, development of novel fluorescent nanoprobes that possess good fluorescent properties, biocompatibility, biodegradability and water dispersibility through a convenient and effective route is still highly desirable. In this work, we reported for the first time that novel fluorescent organic nanoparticles (FONs) can be conveniently fabricated via self-polymerization of dopamine and polyethyleneimine at room temperature and in an air atmosphere within 2 h. These FONs exhibited strong green fluorescence, high water stability and excellent biocompatibility, making them highly potential for biological imaging applications. More importantly, due to the high reactivity of polydopamine, these FONs might also be further functionalized with other functional components through Michael addition or Schiff base reaction. Therefore the method described in this work would open new avenues for the fabrication of fluorescent nanoprobes for various biomedical applications.

Self-healable, super tough graphene oxide–poly(acrylic acid) nanocomposite hydrogels facilitated by dual cross-linking effects through dynamic ionic interactions

Abstract: Here we propose a facile, one-pot in situ free radical polymerization strategy to prepare self-healable, super tough graphene oxide (GO)–poly(acrylic acid) (PAA) nanocomposite hydrogels by using Fe3+ ions as a cross-linker. The 3-dimensional network structure of the GO–PAA nanocomposite hydrogels is facilitated by dual cross-linking effects through dynamic ionic interactions: (i) the first cross-linking points are Fe3+ ions creating ionic cross-linking among PAA chains; (ii) the second cross-linking points are GO nanosheets linking PAA chains through Fe3+ coordination. When the GO–PAA nanocomposite hydrogels are under stretching conditions, the ionic interactions among PAA chains can dynamically break and recombine to dissipate energy, while the GO nanosheets coordinated to the PAA chains maintain the configuration of the hydrogels and work as stress transfer centers transferring the stress to the polymer matrix. In this regard, the GO–PAA nanocomposite hydrogels exhibit superior toughness (tensile strength = 777 kPa, work of extension = 11.9 MJ m−3) and stretchability (elongation at break = 2980%). Furthermore, after being treated at 45 °C for 48 h, the cut-off GO–PAA nanocomposite hydrogels exhibit good self-healing properties (tensile strength = 495 kPa, elongation at break = 2470%). The self-healable, super tough GO–PAA nanocomposite hydrogels lay a basis for developing advanced soft materials holding potential applications in modern biomedical engineering and technology.

Nanoparticle based fluorescence resonance energy transfer (FRET) for biosensing applications

Abstract: In the past few decades, Forster resonance energy transfer (FRET) has been used as a powerful tool for providing nanoscale information in many biosensing and bioanalysis applications. The performance of FRET assays is mainly dependent on the design of donor and acceptor pairs. Recently, a series of nanoparticles start to be used in FRET assays including semiconductor quantum dots (QDs), graphene quantum dots (GQDs), upconversion nanoparticles (UCNPs), gold nanoparticles (AuNPs) and graphene oxide (GO). The rapid pace of development in nanoparticles provides a lot of opportunities to revolutionize FRET techniques. Many nanoparticle based FRET assays have also been developed for various biosensing applications with higher sensitivity and better stability compared with traditional organic fluorophore based FRET assays. This article reviews the recent progress of nanoparticle FRET assays and their applications in biosensing area.

Electrospinning graphene quantum dots into a nanofibrous membrane for dual-purpose fluorescent and electrochemical biosensors

Abstract: Graphene quantum dots (GQDs) have become increasingly important for applications in energy materials, optical devices and biosensors. Here we report a facile technique to fabricate a nanofibrous membrane of GQDs by electrospinning water-soluble GQDs with polyvinyl alcohol (PVA) directly. The structure and fluorescence properties of the fabricated PVA/GQD nanofibrous membrane were investigated using scanning and transmission electron microscopy, and fluorescence microscopy. It was found that the electrospun PVA/GQD nanofibrous membrane has a three-dimensional structure with a high surface area to volume ratio, which is beneficial for the adsorption of electrolytes and the diffusion of reactants. For the first time, the created PVA/GQD nanofibrous membrane was utilized to fabricate dual-purpose fluorescent and electrochemical biosensors for highly sensitive determination of hydrogen peroxide (H2O2) and glucose. The experimental results indicated that the fluorescence intensity of the nanofibrous membrane decreased linearly with increasing H2O2 concentration, because the addition of H2O2 leads to fluorescence quenching of the GQDs, which endows the fabricated nanofibrous membrane with fluorescence activity. Besides, after binding glucose oxidase onto the created nanofibrous membrane, the fabricated nanofibrous membrane showed high sensitivity and selectivity for glucose detection. In addition, the PVA/GQD nanofibrous membrane can also be directly electrospun onto an electrode for electrochemical detection of H2O2. This novel nanofibrous membrane exhibits excellent catalytic performance and fluorescence activity, and therefore has potential applications for the highly stable, sensitive, and selective detection of H2O2 and glucose.

Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices

Abstract: Polymeric biomaterials have a significant impact in today's health care technology. Polymer hydrogels were the first experimentally designed biomaterials for human use. In this article the design, synthesis and properties of hydrogels, derived from synthetic and natural polymers, and their use as biomaterials in tissue engineering are reviewed. The stimuli-responsive hydrogels with controlled degradability and examples of suitable methods for designing such biomaterials, using multidisciplinary approaches from traditional polymer chemistry, materials engineering to molecular biology, have been discussed. Examples of the fabrication of polymer-based biomaterials, utilized for various cell type manipulations for tissue re-generation are also elaborated. Since a highly porous three-dimensional scaffold is crucially important in the cellular process, for tissue engineering, recent advances in the effective methods of scaffold fabrication are described. Additionally, the incorporation of factor molecules for the enhancement of tissue formation and their controlled release is also elucidated in this article. Finally, the future challenges in the efficient fabrication of effective polymeric biomaterials for tissue regeneration and medical device applications are discussed.

An injectable hydrogel formed by in situ cross-linking of glycol chitosan and multi-benzaldehyde functionalized PEG analogues for cartilage tissue engineering

Abstract: In this study, a multi-benzaldehyde functionalized poly(ethylene glycol) analogue, poly(ethylene oxide-co-glycidol)-CHO (poly(EO-co-Gly)-CHO), was designed and synthesized for the first time, and was applied as a cross-linker to develop an injectable hydrogel system. Simply mixing two aqueous precursor solutions of glycol chitosan (GC) and poly(EO-co-Gly)-CHO led to the formation of chemically cross-linked hydrogels under physiological conditions in situ. The cross-linking was attributed to a Schiff's base reaction between amino groups of GC and aldehyde groups of poly(EO-co-Gly)-CHO. The gelation time, water uptake, mechanical properties and network morphology of the GC/poly(EO-co-Gly) hydrogels were well modulated by varying the concentration of poly(EO-co-Gly)-CHO. Degradation of the in situ formed hydrogels was confirmed both in vitro and in vivo. The integrity of the GC/poly(EO-co-Gly) hydrogels was subcutaneously maintained for up to 12 weeks in ICR mice. The feasibility of encapsulating chondrocytes in the GC/poly(EO-co-Gly) hydrogels was assessed. Live/Dead staining assay demonstrated that the chondrocytes were highly viable in the hydrogels, and no dedifferentiation of chondrocytes was observed after 2 weeks of in vitro culture. Cell counting kit-8 assay gave evidence of the remarkably sustained proliferation of the encapsulated chondrocytes. Maintenance of the chondrocyte phenotype was also confirmed with an examination of characteristic gene expression. These features suggest that GC/poly(EO-co-Gly) hydrogels hold potential as an artificial extracellular matrix for cartilage tissue engineering.

Processable conducting graphene/chitosan hydrogels for tissue engineering

Abstract: Composites of graphene in a chitosan–lactic acid matrix were prepared to create conductive hydrogels that are processable, exhibit tunable swelling properties and show excellent biocompatibility. The addition of graphene to the polymer matrix also resulted in significant improvements to the mechanical strength of the hydrogels, with the addition of just 3 wt% graphene resulting in tensile strengths increasing by over 200%. The composites could be easily processed into three-dimensional scaffolds with finely controlled dimensions using additive fabrication techniques and fibroblast cells demonstrate good adhesion and growth on their surfaces. These chitosan–graphene composites show great promise for use as conducting substrates for the growth of electro-responsive cells in tissue engineering.

Engineering highly stretchable lignin-based electrospun nanofibers for potential biomedical applications

Abstract: Lignin, one of the most abundant biopolymers on Earth, has been recognized as a renewable alternative to traditional petroleum-based plastics. The integration of lignin with synthetic and engineering plastics is an important approach to develop sustainable polymers. However, it is challenging to blend lignin with other polymers due to its brittle nature and poor dispersion in many composites. In order to improve the miscibility and compatibility of lignin with other plastics, a series of poly(methyl methacrylate) (PMMA) grafted lignin copolymers were prepared from atom transfer radical polymerization. The chain length of PMMA oligomers and glass transition temperature of the lignin copolymers was controlled by varying the lignin: methyl methacrylate ratio. The lignin mass fractions in the copolymers varied from 5.6% to 46.1%. These lignin–PMMA copolymers were further blended with poly(e-caprolactone) (PCL) and engineered into nanofibrous composites by electrospinning. Tensile test and dynamical mechanical analysis showed that the incorporation of lignin–PMMA copolymers significantly improved the tensile strength, Young's modulus, and storage modulus of the resulting nanofibrous composites. The length of the PMMA chain played a crucial role in the miscibility of lignin in PCL, and therefore enhanced the stiffness and ultimate elongation of the resulting nanofibers. Cell culture studies suggested that these PCL/lignin–PMMA nanofibers were biocompatible and promoted the proliferation, attachment and interactions of human dermal fibroblasts. With reinforced mechanical properties and good biocompatibility, these green and stretchable electrospun nanofibers are potentially useful as biomaterial substrates for biomedical applications.

Enhanced colloidal stability and antibacterial performance of silver nanoparticles/cellulose nanocrystal hybrids.

Abstract: The aggregation of nanoparticles has been shown to significantly reduce the activity of nanomaterials, resulting in inferior performance. As an alternative to the use of traditional capping agents, stabilization of unstable nanoparticles with water-dispersible and biocompatible carriers is a promising strategy. A bioinspired coating strategy was developed and the hybrid nanoparticles displayed excellent colloidal stability that significantly improved antibacterial activity when silver nanoparticles (AgNPs) were used as a model. Cellulose nanocrystals (CNCs) were first modified with dopamine, followed by in situ generation and anchoring of AgNPs on the surface of CNCs through the reduction of silver ions by polydopamine coated CNCs. The results indicated that the dispersion stability of AgNPs was significantly enhanced by the CNC, which in turn resulted in more than fourfold increase in antibacterial activity based on antibacterial studies using Escherichia coli and Bacillus subtilis.

An enzyme–inorganic hybrid nanoflower based immobilized enzyme reactor with enhanced enzymatic activity

Abstract: A facile approach for the synthesis of enzyme–inorganic hybrid nanoflowers and their application as an immobilized α-chymotrypsin (ChT) reactor (IMER) for highly efficient protein digestion was described. The hybrid nanoflowers were room-temperature synthesized in aqueous solution using calcium phosphate (Ca3(PO4)2) as the inorganic component and ChT as the organic component. The effects of reaction parameters on the formation of the enzyme-embedded hybrid nanoflowers and their growth mechanism were investigated systematically. By monitoring the reaction of N-benzoyl-L-tyrosine ethyl ester (BTEE), the enzymatic activity of the immobilized ChT was calculated and the results showed 266% enhancement in enzymatic activity. The performance of such a nanoreactor was further demonstrated by digesting bovine serum albumin (BSA) and human serum albumin (HSA), with a stringent threshold for unambiguous identification of these digests, the yielding sequence coverages for nanoflower-based digestion were 48% and 34%, higher than those obtained with the free enzyme. The digestion time of BSA and HSA in the former case was less than 2 min, about 1/360 of that performed in the latter case (12 h). Furthermore, the residual activity of the nanoflowers decreased slightly even after eight repeated use, demonstrating promising stability. In addition, the hybrid nanoflower-based IMER was applicable to the digestion of a complex human sample, showing great promise for proteome analysis.

Rational design and applications of conducting polymer hydrogels as electrochemical biosensors

Abstract: Conducting polymer hydrogels (CPHs) are conducting polymer-based materials that contain high water content and have physical properties, resembling the extracellular environment. Synergizing the advantages of both the organic conductors and hydrogels, CPHs emerged to be candidates for high performance biosensors by providing advantageous interfaces for electrochemical bio-electrodes. Examples include the following: (1) the interface between a biomaterial and an artificial inorganic electrode material; (2) the hybrid electronic interface between an ionic carrier and an electron charge carrier; and (3) the extension of the planar electrode surface to a three-dimensional (3D) porous surface. CPHs with rationally designed 3D nanostructures and molecular structures are advantageous for enhancing the biocompatibility of the electrode, improving enzyme immobilization, creating protective layers to control diffusion, and wiring the electron transference. This review presents a brief overview of the current state-of-the-art research in electrochemical biosensors based on CPHs and describes future directions.

3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration

Abstract: When large engineered tissue structures are used to achieve tissue regeneration, formation of vasculature is an essential process. We report a technique that combines 3D printing with spatial and temporal control of dual growth factors to prevascularize bone tissue. Human dental pulp stem cells (DPSCs) that have both osteogenic and vasculogenic potential were printed with bone morphogenetic protein-2 (BMP-2) in the peripheral zone of the 3D printed construct, and with the vascular endothelial growth factor (VEGF) in the central zone, in which a hypoxic area forms. The structure was implanted in the back of a mouse and tissue regeneration was assessed after 28 d. Microvessels were newly formed in the hypoxic area of the printed large volume structure, and angiogenesis from the host tissue was also observed. Bone regeneration was faster in prevascularized structures than in nonvascularized structures. The 3D-printed prevascularized structure could be a promising approach to overcome the size limitation of tissue implants and to enhance bone regeneration.

Gold-graphene nanocomposites for sensing and biomedical applications.

Abstract: Recent developments in materials science and nanotechnology have propelled the development of a plethora of materials with unique chemical and physical properties for biomedical applications. Graphitic nanomaterials such as carbon nanotubes, fullerenes and, more recently, graphene oxide (GO) and reduced graphene oxide (rGO) have received a great deal of interest in this domain. Besides the exceptional physico-chemical features of these materials, another advantage is that they can be easily produced in good quantities. Moreover, the presence of abundant functional groups on their surface and good biocompatibility make them highly suitable for biomedical applications. Many research groups have utilized GO and rGO nanocargos to effectively deliver insoluble drugs, nucleic acids and other molecules into cells for bioimaging and therapeutic purposes. Gold nanostructures (Au NSs), on the other hand, have also attracted great attention owing to their applications in biomedical fields, organic catalysis, etc. Loading of GO and rGO sheets with Au NSs generates a new class of functional materials with improved properties and thus provides new opportunities in the use of such hybrid materials for catalytic biosensing and biomedical applications. This review article is aimed at providing an insight into the important features of gold–graphene nanocomposites, the current research activities related to the different synthetic routes to produce these nanocomposites, and their potential applications in sensing and biomedical therapy, notably photothermal therapy (PTT).

Low temperature synthesis of phosphorous and nitrogen co-doped yellow fluorescent carbon dots for sensing and bioimaging

Abstract: Phosphorous and nitrogen co-doped carbon dots (P,N-CDs) with satisfactory quantum yield have been prepared through one-step acidic oxidation of pumpkin by H3PO4 at low temperature (90 °C). The as-prepared P,N-CD is relatively monodisperse with a narrow size distribution. The P,N-CD displays a remarkable emission enhancement in the yellow fluorescence region (λem = 550 nm) when the pH is increased from 1.5 to 7.4. The pKa value of P,N-CDs was found to be 4.17 and it shows linear response to the physiological range of pH 4.7–7.4, which is valuable for near-neutral cytosolic pH research. It is observed that P,N-CDs are superior fluorescent bioimaging agents in animals and cells thanks to their excellent solubility and ultra-low toxicity. In addition, P,N-CDs display a notably large Stokes shift of 125 nm, good reversibility and could effectively avoid the influence of autofluorescence in biological systems. The confocal fluorescent microscopic images of subcellular distribution and the detection of pH in MCF-7 cells were achieved successfully, suggesting that P,N-CDs have excellent cell membrane permeability and are further applied successfully to monitor pH fluctuations in live cells with negligible autofluorescence.

Polymeric multifunctional nanomaterials for theranostics

Abstract: Nanocarriers provide a platform to integrate therapy and diagnostics, which is an emerging direction in medical practice. Beyond simply therapeutic functionality, theranostic nanomaterials have been designed to deliver multiple components and imaging agents, facilitating simultaneous and synergistic diagnosis and therapies. In this article, polymeric materials with diverse functionalities and properties for manufacturing theranostic nanomaterials are discussed and compared. We focused on recent advancements in polymeric multifunctional nanomaterials for synergistic theranostics. The drugs and imaging agents were encapsulated within and/or conjugated to the surface of the nanocarriers, according to the fabrication process and carrier type. In parallel with therapy, polymeric multifunctional nanomaterials can be exploited to exhibit distinctive magnetic, electrical, and optical properties for concomitant imaging. This has been accomplished by incorporating various imaging agents, such as fluorescent dyes, biomarkers, quantum dots, metal composites, and magnetic nanoparticles. We discussed theranostic nanomaterial synthesis, carrier fabrication and its applications. By presenting this comprehensive review of the state-of-the-art, we demonstrated that polymeric multifunctional nanomaterials exhibit distinctive advantages and features in theranostics.

A colorimetric and ratiometric fluorescent probe for ClO- targeting in mitochondria and its application in vivo.

Abstract: A colorimetric and ratiometric fluorescent probe PMN–TPP for imaging mitochondrial ClO− was prepared. The selectivity of PMN–TPP was excellent and the detection would not be influenced by other ROS. The limit of detection (LOD = 3σ/slope) for ClO− was evaluated to be 0.43 μM, suggesting the probe's high sensitivity to ClO−. For the biological applications, PMN–TPP performed well in detecting endogenous HClO in living RAW264.7 macrophage cells. A co-localization study employing Mito Tracker green revealed that PMN–TPP was specifically located in the mitochondria of living RAW264.7 macrophage cells. In the in vivo experiment, a nude mouse with acute inflammation stimulated by lipopolysaccharide (LPS) was employed. After injection of PMN–TPP, the fluorescence signal changed gradually in 30 min and then remained unchanged in the injection region, demonstrating that PMN–TPP could detect the endogenous HClO in living animals.

Fibrous wound dressings encapsulating essential oils as natural antimicrobial agents

Abstract: Preventing infections is one of the main focuses of wound care. The colonisation of wounds by microorganisms can in fact have negative consequences on the healing process, delaying it. Here, we propose the use of essential oils as natural antimicrobial agents for cellulose-based fibrous dressings. We demonstrate the production of composite electrospun fibres that effectively encapsulate three different types of essential oils (cinnamon, lemongrass and peppermint). The fibrous scaffolds are able to inhibit the growth of Escherichia coli, even when small amounts of essential oils were used. At the same time, they are not cytotoxic, as proved by biocompatibility assays on skin cell models. The created dressings are promising as advanced biomedical devices for topical treatments.

Engineering and functionalization of biomaterials via surface modification

Abstract: It is imperative to control the interactions between biomaterials and living tissues to optimize their therapeutic effects and disease diagnostics. Because most biomaterials do not have the perfect surface properties and desirable functions, surface modification plays an important role in tailoring the surface of biomaterials to allow better adaptation to the physiological surroundings and deliver the required clinical performance. This paper reviews recent progress pertaining to the surface treatment of implantable macro-scale biomaterials for orthopedic and dental applications as well as micro- and nano-biomaterials for disease diagnosis and drug/gene delivery. Recent advances in surface modification techniques encompassing adsorption, deposition, ion implantation, covalent binding, and conversion have spurred more expeditious development of new-generation biomaterials.

Enzymatic electrochemical glucose biosensors by mesoporous 1D hydroxyapatite-on-2D reduced graphene oxide

Abstract: A novel hydrothermal process was used for the preparation of hydroxyapatite (HAp) nanorods on two-dimensional reduced graphene oxides (RGO). The hydrothermal reaction temperature improves the crystallinity of HAp and partially reduces graphene oxide (GO) to RGO. The crystalline structure, chemical composition and morphology of the prepared nanocomposites were characterized by using various analytical techniques. Nanorods of HAp with a diameter and length of ∼32 and 60–85 nm were grown on basal planes and edges of the layered RGO sheets. The estimated specific surface area and pore-size distribution are 120 m2 g−1 and 5.6 nm, respectively. We also report the direct electrochemistry of glucose oxidase (GOx) on 1D HAp-on-2D RGO nanocomposite-modified glassy carbon electrode (GCE) for glucose sensing. The electrocatalytic and electroanalytical applications of the proposed RGO/HAp/GOx-modified GCE were studied by cyclic voltammetry (CV) and amperometry. The increased electron rate constant of 3.50 s−1 was obtained for the modified GCE. The reported biosensor exhibits a superior detection limit and higher sensitivity ca. 0.03 mM and 16.9 μA mM−1 cm−2, respectively, with a wide linear range of 0.1–11.5 mM. The tremendous analytical parameters of the reported sensor surpass those of related modified electrodes and are promising for practical industrial applications.

Green preparation of fluorescent carbon dots from lychee seeds and their application for the selective detection of methylene blue and imaging in living cells

Abstract: A green approach was developed for the preparation of fluorescent carbon dots (CDs) by using lychee seeds as precursors. The preparation of CDs was performed by simple pyrolysis. The quantum yield of as-prepared CDs was 10.6% by using quinine sulfate as the reference. The CDs were employed as fluorescence probes for the detection of methylene blue (MB). This sensing system exhibits excellent sensitivity and selectivity toward MB, and a detection limit of 50 mM is achieved. The possible application of as-prepared CDs for imaging in living cells was also explored. The inherent cytotoxicity of CDs was evaluated using HepG2 cell, and the cell viabilities were estimated to be greater than 90% upon addition of the CDs over a wide concentration range of 0-1000 μg mL-1. It was then successfully applied for the fluorescence imaging of HepG2 cells.

Amelogenin and Enamel Biomimetics.

Abstract: Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great interest. Considering the importance of amelogenin protein in dental enamel formation, its ability to control apatite mineralization in vitro, and its potential to be applied in fabrication of future bio-inspired dental material this review focuses on two major subjects: amelogenin and enamel biomimetics. We review the most recent findings on amelogenin secondary and tertiary structural properties with a focus on its interactions with different targets including other enamel proteins, apatite mineral, and phospholipids. Following a brief overview of enamel hierarchical structure and its mechanical properties we will present the state-of-the-art strategies in the biomimetic reconstruction of human enamel.

A redox-responsive drug delivery system based on RGD containing peptide-capped mesoporous silica nanoparticles

Abstract: In this paper, an intracellular glutathione (GSH) responsive mesoporous silica nanoparticle (MSN-S-S-RGD) was developed as a drug nanocarrier by immobilizing the gatekeeper (RGD containing peptide) onto MSNs using disulfide bonds. The antitumor drug, DOX was loaded onto the porous structure of the MSNs and the DOX@MSN-S-S-RGD system has been proved to be an effective nanocarrier. It was determined that most of the drug could be entrapped with only a slight leakage. After being accumulated in tumor cells via the receptor-mediated endocytosis, the surface peptide layer of DOX@MSN-S-S-RGD was removed to trigger the release of the entrapped drug to kill the tumor cell due to the cleavage of the disulfide bonds by intracellular GSH.

Poly(glycerol sebacate) biomaterial: synthesis and biomedical applications

Abstract: The recently developed poly(glycerol sebacate) (PGS) has been gaining attraction as a biomaterial for tissue engineering applications. Reported in 2002, a simple polycondensation method was developed to synthesize PGS for soft tissue engineering applications. It has since become a highly sought after biomaterial due to its soft, robust and flexible characteristics and it is relatively low cost compared to other biodegradable elastomers currently available in the market. We summarise in this review, the various synthetic approaches of PGS and highlight selected applications in nerve guidance, soft tissue regeneration, vascular and myocardial tissue regeneration, blood vessel reconstruction, drug delivery, and the replacement of photoreceptor cells. A critical assessment of the material is provided as a scope for future improvement. The future outlook of this material is also provided at the end of this review.

A rhodamine B-based lysosomal pH probe

Abstract: A novel rhodamine B-based fluorescent probe (RML) for lysosomal pH was developed by integrating a 4-(2-aminoethyl)morpholine moiety, which is a lysosome-targetable group, into a rhodamine B fluorophore, which is associated with rhodamine B dyes possessing spirocyclic (non-fluorescent) and ring-opening (fluorescent) forms with response to pH. The probe responded to acidic pH at low concentration in a short amount of time. In addition, RML showed good membrane permeability and brilliant selectivity among various amino acids and metal cations. RML exhibited an 80-fold increase in fluorescence intensity at 583 nm throughout the pH range of 7.40–4.00 with a pKa of 5.16, which indicates that RML is valuable for studying intracellular acidic organelles. Moreover, RML has been successfully applied in HeLa cells, and the results demonstrated that RML could selectively stain lysosomes in living HeLa cells. Note that RML could be used to detect the pH increase in lysosomes induced by bafilomycin A1 within HeLa cells.

Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery

Abstract: Here, we report the development of a multifunctional nanocarrier consisting of paramagnetic graphene quantum dots (GQDs), folate, and doxorubicin (Dox), used as delivery vehicles, a targeting ligand, and a chemotherapeutic drug, respectively. The paramagnetic GQDs, named folate–GdGQDs, were successfully prepared by covalently conjugating diethylenetriaminepentaacetic acid gadolinium and folic acid onto the surface of GQDs. The resultant folate–GdGQDs, which showed a longitudinal relaxivity r1 of 11.49 mM−1 s−1, greatly enhanced the brightness of the T1-weighted magnetic resonance (MR) images, indicating their potential for use as positive contrast agents for MR imaging (MRI). The feasibility of utilizing the folate–GdGQDs with strong luminescence emissions for targeted imaging of HeLa cells was also evaluated. An in vitro cell (HeLa and HepG2 cells) viability assay and in vivo evaluation of toxicity to the embryonic development of zebrafish showed that these folate–GdGQDs exhibited negligible cytotoxicity and excellent biocompatibility within the given range of concentrations. More importantly, strong therapeutic activity was achieved by loading Dox onto the surfaces of folate–GdGQDs through π–π stacking and hydrophobic interactions, leading to the formation of folate–GdGQD/Dox multifunctional nanocarriers. Approximately 80% of the loaded Dox was released from the folate–GdGQD/Dox nanocarriers under mild acidic conditions (pH 5.0), whereas only 20% of Dox was released at pH 7.0 after 48 h. Furthermore, these multifunctional nanocarriers could efficiently induce an inhibitory effect on HeLa cells, as confirmed by an in vitro cytotoxicity assay. The combined flow cytometry analysis and confocal laser scanning microscopic observation showed that these nanocarriers were efficiently taken up by the cancer cells overexpressing folate receptors. Taken together, these results suggested that the multifunctional nanocarriers could be used as promising targeted drug delivery vehicles for the diagnosis and image-guided chemotherapy of various cancers.

Thermo/redox/pH-triple sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogels for anticancer drug delivery.

Abstract: The clinical application of doxorubicin (DOX), like other anticancer drugs, is limited by insufficient cellular uptake and the numerous drug resistance mechanisms existing in cells. The development of smart nanomaterials capable of carrying the drugs into the cells and of releasing them under the control of the microenvironment is an interesting approach that may increase the success of the anticancer drugs currently in use. Herein, we report an easy process to prepare biocompatible nanogels (NGs) with thermo/redox/pH-triple sensitivity, which are highly effective in the intracellular delivery of DOX. Redox-sensitive/degradable NGs (PNA-BAC) and nondegradable NGs (PNA-MBA) were prepared through in situ polymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of sodium dodecyl sulfate (SDS) as a surfactant, using N,N′-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker or N,N′-methylene bisacrylamide (MBA) as a nondegradable crosslinker, respectively. After that, the cationic DOX drug was loaded into the NGs through electrostatic interactions, by simply mixing them in aqueous solution. Compared to nondegradable PNA-MBA NGs, PNA-BAC NGs not only presented a higher DOX drug loading capacity, but also allowed a more sustainable drug release behavior under physiological conditions. More importantly, PNA-BAC NGs displayed thermo-induced drug release properties and an in vitro accelerated release of DOX under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The thermo/redox/pH multi-sensitive NGs can quickly be taken up by CAL-72 cells (an osteosarcoma cell line), resulting in a high DOX intracellular accumulation and an improved cytotoxicity when compared with free DOX and DOX-loaded nondegradable PNA-MBA NGs. The developed NGs can be possibly used as an effective platform for the delivery of cationic therapeutic agents for biomedical applications.

Synthesis of silver nanoparticles for the dual delivery of doxorubicin and alendronate to cancer cells

Abstract: We present the synthesis of a silver nanoparticle (AgNP) based drug-delivery system that achieves the simultaneous intracellular delivery of doxorubicin (Dox) and alendronate (Ald) and improves the anticancer therapeutic indices of both drugs. Water, under microwave irradiation, was used as the sole reducing agent in the size-controlled, bisphosphonate-mediated synthesis of stabilized AgNPs. AgNPs were coated with the bisphosphonate Ald, which templated nanoparticle formation and served as a site for drug attachment. The unreacted primary ammonium group of Ald remained free and was subsequently functionalized with either Rhodamine B (RhB), through amide formation, or Dox, through imine formation. The RhB-conjugated NPs (RhB–Ald@AgNPs) were studied in HeLa cell culture. Experiments involving the selective inhibition of cell membrane receptors were monitored by confocal fluorescence microscopy and established that macropinocytosis and clathrin-mediated endocytosis were the main mechanisms of cellular uptake. The imine linker of the Dox-modified nanoparticles (Dox–Ald@AgNPs) was exploited for acid-mediated intracellular release of Dox. We found that Dox–Ald@AgNPs had significantly greater anti-cancer activity in vitro than either Ald or Dox alone. Ald@AgNPs can accommodate the attachment of other drugs as well as targeting agents and therefore constitute a general platform for drug delivery.