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Background: Craniosynostosis is a developmental disorder characterized by the premature fusion of skull sutures, necessitating repetitive, high-risk neurosurgical interventions throughout infancy. This study used protein-releasing Titania nanotubular implant (TNT/Ti) loaded with glypican 3 (GPC3) in the cranial critical-sized defects (CSDs) in Crouzon murine model ( Fgfr2 c342y/+ knock-in mutation) to address a key challenge of delaying post-operative bone regeneration in craniosynostosis., Materials and Methods: A 3 mm wide circular CSD was created in two murine models of Crouzon syndrome: (i) surgical control (CSDs without TNT/Ti or any protein, n=6) and (ii) experimental groups with TNT/Ti loaded with GPC3, further subdivided into the presence or absence of chitosan coating (on nanotubes) (n=12 in each group). The bone volume percentage in CSDs was assessed 90 days post-implantation using micro-computed tomography (micro-CT) and histological analysis., Results: Nano-implants retrieved after 90 days post-operatively depicted well-adhered, hexagonally arranged, and densely packed nanotubes with average diameter of 120±10 nm. The nanotubular architecture was generally well-preserved. Compared with the control bone volume percentage data (without GPC3), GPC3-loaded TNT/Ti without chitosan coating displayed a significantly lower volume percent in cranial CSDs ( P <0.001). Histological assessment showed relatively less bone regeneration (healing) in GPC3-loaded CSDs than control CSDs., Conclusion: The finding of inhibition of cranial bone regeneration by GPC3-loaded TNT/Ti in vivo is an important advance in the novel field of minimally-invasive craniosynostosis therapy and holds the prospect of altering the whole paradigm of treatment for affected children. Future animal studies on a larger sample are indicated to refine the dosage and duration of drug delivery across different ages and both sexes with the view to undertake human clinical trials., Competing Interests: The authors declare no conflicts of interest in this work.

Introduction: Therapeutics delivery to bones to treat skeletal diseases or prevent postsurgical infections is challenging due to complex and solid bone structure that limits blood supply and diffusion of therapeutics administered by systemic routes to reach effective concentration. Titanium (Ti) and their alloys are employed as mainstream implant materials in orthopedics and dentistry; having superior mechanical/biocompatibility properties which could provide an alternative solution to address this problem., Areas Covered: This review presents an overview of recent development of Ti drug-releasing implants, with emphasis on nanoengineered Titania nanotubes (TNTs) structures, for solving key problems to improve implants osseointegration, overcome inflammation and infection together with providing localized drug delivery (LDD) for bone diseases including cancer. Critical analysis of the advantages/disadvantages of developed concepts is discussed, their drug loading/releasing performances and specific applications., Expert Opinion: LDD to bones can address many disorders and postsurgical conditions such as inflammation, implants rejection and infection. To this end, TNTs-Ti implants represent a potential promise for the development of new generation of multifunctional implants with drug release functions. Even this concept is extensively explored recently, there is a strong need for more preclinical studies using animal models to confirm the long-term safety and stability of TNTs-Ti implants for real-life medical applications.

The success of implantation of materials into bone is governed by effective osseointegration, requiring biocompatibility of the material and the attachment and differentiation of osteoblastic cells. To enhance cellular function in response to the implant surface, micro- and nano-scale topography have been suggested as essential. In this study, we present bone implants based on 3D-printed titanium alloy (Ti6Al4V), with a unique dual topography composed of micron-sized spherical particles and vertically aligned titania nanotubes. The implants were prepared by combination of 3D-printing and anodization processes, which are scalable, simple and cost-effective. The osseointegration properties of fabricated implants, examined using human osteoblasts, showed enhanced adhesion of osteoblasts compared with titanium materials commonly used as orthopaedic implants. Gene expression studies at early (day 7) and late (day 21) stages of culture were consistent with the Ti substrates inducing an osteoblast phenotype conducive to effective osseointegration. These implants with the unique combination of micro- and nano-scale topography are proposed as the new generation of multi-functional bone implants, suitable for addressing many orthopaedic challenges, including implant rejection, poor osseointegration, inflammation, drug delivery and bone healing. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Titania nanotubes (TNTs) engineered on titanium (Ti) surfaces (i.e. TNT/Ti) and loaded with specific drugs have been recognised as a promising solution for localised therapeutic delivery to address several medical problems not feasible with conventional drug administration. We propose the use of TNT/Ti protein-releasing implants to treat paediatric craniofacial abnormality in craniosynostosis caused by premature fusion of cranial sutures. In this study, we have analysed the biological response of human suture mesenchymal cells (SMCs), extracted from two different patients undergoing craniofacial reconstruction surgery, at the TNT/Ti implant surface. The experimental groups included large-diameter TNT/Ti implants, with and without biopolymer surface coating (Chitosan and Pluronic-F127) while the controls comprised of flat Ti disc and tissue culture plastic. The non-loaded implant surfaces and the cellular interactions at the implant-cell interface were characterised using scanning electron microscopy (SEM). The SMC adhesion, viability and proliferation were determined by MTT assay and manual cell counting at day 1 and day 3 of cell incubation. SEM showed significant reduction in initial attachment and adhesion of SMCs at TNT-cell biointerface compared with the control Ti discs. Subsequent cell proliferation results also revealed a decrease in the number of viable cells on the TNT surfaces. The nanotopography and structural features along with the surface chemistry dictated the cellular response, with nanotubular surfaces (with and without polymer coating) impeding cell adhesion and proliferation. Our findings hold promise for the use of TNT-based cranial implants as a delivery system to prevent sutural bone growth for advanced craniosynostosis therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach. Previously, we reported the design and fabrication of nano-engineered 3D titanium wire based implants with titania (TiO2) nanotube arrays (Ti-TNTs) for applications such as bone integration by using in-vitro culture systems. The aim of present study is to demonstrate the feasibility of using such Ti-TNTs loaded with anti-cancer agent for localized cancer therapy using pre-clinical cancer models and to test local drug delivery efficiency and anti-tumour efficacy within the tumour environment. TNF-related apoptosis-inducing ligand (TRAIL) which has proven anti-cancer properties was selected as the model drug for therapeutic delivery by Ti-TNTs. Our in-vitro 2D and 3D cell culture studies demonstrated a significant decrease in breast cancer cell viability upon incubation with TRAIL loaded Ti-TNT implants (TRAIL-TNTs). Subcutaneous tumour xenografts were established to test TRAIL-TNTs implant performance in the tumour environment by monitoring the changes in tumour burden over a selected time course. TRAIL-TNTs showed a significant regression in tumour burden within the first three days of implant insertion at the tumour site. Based on current experimental findings these Ti-TNTs wire implants have shown promising capacity to load and deliver anti-cancer agents maintaining their efficacy for cancer treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Titanium implants can fail due to inappropriate biomechanics at the bone-implant interface that leads to suboptimal osseointegration. Titania nanotubes (TNTs) fabricated on Ti implants by the electrochemical process have emerged as a promising modification strategy to facilitate osseointegration. TNTs enable augmentation of bone cell functions at the bone-implant interface and can be tailored to incorporate multiple functionalities including the loading of active biomolecules into the nanotubes to target anabolic processes in bone conditions such as osteoporotic fractures. Advanced functions can be introduced, including biopolymers, nanoparticles and electrical stimulation to release growth factors in a desired manner. This review describes the application of TNTs for enhancing osteogenesis at the bone-implant interface, as an alternative approach to systemic delivery of therapeutic agents.

Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs-induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy.

Here, we report on the development of advanced biopolymer-coated drug-releasing implants based on titanium (Ti) featuring titania nanotubes (TNTs) on its surface. These TNT arrays were fabricated on the Ti surface by electrochemical anodization, followed by the loading and release of a model antibiotic drug, gentamicin. The osteoblastic adhesion and antibacterial properties of these TNT-Ti samples are significantly improved by loading antibacterial payloads inside the nanotubes and modifying their surface with two biopolymer coatings (PLGA and chitosan). The improved osteoblast adhesion and antibacterial properties of these drug-releasing TNT-Ti samples are confirmed by the adhesion and proliferation studies of osteoblasts and model Gram-positive bacteria (Staphylococcus epidermidis). The adhesion of these cells on TNT-Ti samples is monitored by fluorescence and scanning electron microscopies. Results reveal the ability of these biopolymer-coated drug-releasing TNT-Ti substrates to promote osteoblast adhesion and proliferation, while effectively preventing bacterial colonization by impeding their proliferation and biofilm formation. The proposed approach could overcome inherent problems associated with bacterial infections on Ti-based implants, simultaneously enabling the development of orthopedic implants with enhanced and synergistic antibacterial functionalities and bone cell promotion., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Here, we report a detailed and systematic approach for studying the in vitro nanotoxicity study of high aspect ratio (HAR) nanomaterials using anodic alumina nanotubes (AANTs) as a nanomaterial model. AANTs with bio-inert properties and tailored aspect ratios ranging from 7.8 to 63.3 were synthesized by an electrochemical pulse anodization process. Cytotoxicity studies were conducted with RAW 264.7 mouse macrophage cells and MDA-MB 231-TXSA human breast cancer cells through several toxicity parameters, including cell viability and morphology, pro-inflammatory response, mitochondrial depolarization, lysosomal membrane permeabilization (LMP), induction of autophagy and endoplasmic reticulum (ER) stress. The resulting toxicity patterns were cell-type dependent and strongly related with AANTs dose, length of time, and importantly the AR of AANTs. Long AANTs triggered enhanced cell death, morphological changes, tumor necrosis factor α (TNF-α) release, LMP and ER stress than short AANTs. The toxic AR window of AANTs was determined to be 7.8, which is shorter than that of other previously reported HAR nanomaterials. This toxic AR window provides a promising opportunity to control the nanotoxicity of HAR nanomaterials for their advanced drug delivery application., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Titania nanotube (TNTs) arrays engineered by simple and scalable electrochemical anodization process have been extensively explored as a new nanoengineering approach to address the limitations of systemic drug administration. Due to their outstanding properties and excellent biocompatibility, TNTs arrays have been used to develop new drug-releasing implants (DRI) for emerging therapies based on localized drug delivery (DD). This review highlights the concepts of DRI based on TNTs with a focus on recent progress in their development and future perspectives towards advanced medical therapies., Areas Covered: Recent progress in new strategies for controlling drug release from TNTs arrays aimed at designing TNTs-based DRI with optimized performances, including extended drug release and zero-order release kinetics and remotely activated release are described. Furthermore, significant progress in biocompatibility studies on TNTs and their outstanding properties to promote hydroxyapatite and bone cells growths and to differentiate stem cells are highlighted. Examples of ex vivo and in vivo studies of drug-loaded TNTs are shown to confirm the practical and potential applicability of TNTs-based DRI for clinical studies. Finally, selected examples of preliminary clinical applications of TNTs for bone therapy and orthopedic implants, cardiovascular stents, dentistry and cancer therapy are presented., Expert Opinion: As current studies have demonstrated, TNTs are a remarkable material that could potentially revolutionize localized DD therapies, especially in areas of orthopedics and localized chemotherapy. However, more extensive ex vivo and in vivo studies should be carried out before TNTs-based DRI could become a feasible technology for real-life clinical applications. This will imply the implementation of different approaches to overcome some technical and commercial challenges.

Here, we report a study on the biocompatibility, cell uptake and in vitro delivery of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) by new nano-carriers called anodic alumina nanotubes (AANTs) for potential cancer therapy. AANTs were electrochemically engineered by a unique pulse anodization process, which enables precise control of the nanotube geometry, and used here as nano-carriers for drug delivery. In vitro cytotoxicity and cell uptake of AANTs was assessed using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells. AANTs exhibited excellent biocompatibility in both cell lines over a time course of five days even at a maximum concentration of AANTs of 100 μgmL(-1). Transmission electron microscopy and fluorescence microscopy confirmed a significant uptake of AANTs by RAW 264.7 cells and breast cancer cells. AANTs loaded with the pro-apoptotic protein Apo2L/TRAIL showed exceptional loading capacity (104 ± 14.4 μgmg(-1) of AANTs) and demonstrated significant decrease in viability of MDA-MB231-TXSA cancer cells due to apoptosis induction. These results demonstrate that AANTs are promising nano-carriers for drug delivery applications., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Aim: This study aimed to demonstrate radiofrequency (RF)-triggered release of drugs and drug carriers from drug-eluting implants using gold nanoparticles as energy transducers., Materials & Methods: Titanium wire with a titania nanotube layer was used as an implant loaded with indomethacin and micelles (tocopheryl PEG succinate) as a drug and drug carrier model. RF signals were generated from a customized RF generator to trigger in vitro release., Results & Discussion: Within 2.5 h, 18 mg (92%) of loaded drug and 14 mg (68%) of loaded drug carriers were released using short RF exposure (5 min), compared with 5 mg (31%) of drug and 2 mg (11%) of drug carriers without a RF trigger. Gold nanoparticles can effectively function as RF energy transducers inside titania nanotubes for rapid release of therapeutics at arbitrary times., Conclusion: The results of this study show that RF is a promising strategy for triggered release from implantable drug delivery systems where on-demand delivery of therapeutics is required.

A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin)., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Titania nanotube (TNT) arrays fabricated by electrochemical anodization of titanium are currently one of the most attractive nanomaterials due to their remarkable properties. In this review, we highlight recent research activities that are focused on the application of the TNT arrays for local drug delivery, specifically for addressing problems associated with orthopedic implants. The advantages of drug-releasing implants based on TNT arrays for local delivery of therapeutics in bone related to these challenging problems including inflammation, infection and osseointegration are discussed. An overview of recent research to advance the drug-releasing performance of TNT arrays and the potential of their future applications and development are presented.

A multi-drug delivery system with sequential release based on titania nanotube arrays and polymer micelles as drug carriers is presented. Delivery of multiple water insoluble and soluble drugs required for combined local therapy is demonstrated.

Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery, Methods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT-Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0-5 mm) and horizontal (0-10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days., Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT-Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT-Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone., Conclusion: These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.

Nanotubular titanium oxide (TiO(2)) produced by self-ordering processes using electrochemical anodization have been extensively explored in recent years as a new biomaterial for implants, drug delivery systems, cell growth, biosensors, immunoisolations, bioartificial organs and tissue engineering. Chemical inertness is the main weakness of this material when placed in contact with biological systems and surface modification is a possible solution of this problem. The aim of this study is to develop a flexible and facile method for surface modification of TiO(2) nanotubes to tailor new interfacial properties important in many biomedical applications. TiO(2) nanotubes were prepared by electrochemical anodization of titanium foil using ethylene glycol: NH(4)F electrolyte (2% water and 0.3% NH(4)F). Plasma surface modification using allylamine (AA) as a precursor has been applied to generate a thin and chemically reactive polymer (AAPP) film rich in amine groups on top of the TiO(2) nanotube surface. This initial polymer film was used for further surface functionalization by attachment of desired molecules. Two modification techniques were used to demonstrate the flexibility for building of new functionalities on titania nanotube surface: electrostatic adsorption of poly(sodium styrenesulfonate) (PSS) as an example of layer-by-layer assembly (LbL), and covalent coupling of poly(ethylene glycol) (PEG) as an example of creating a protein-resistant surface. These approaches for tailoring the surface chemistry and wettability of TiO(2) nanotubes offer considerable prospects for advancing their interfacial properties to improve existing and develop new functional biomaterials for diverse biomedical applications.

Abstract Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies. This study presents the application of nanoengineered TNT/Ti implants loaded with recombinant glypicans for craniosynostosis therapy. By using Dual luciferase Reporter assay, we tested the biofunctionality of eluted glypicans from the TNT/Ti implants for BMP2 bioactivity regulation in C2C12 murine myoblast cell line. BMP2 activity was inhibited significantly for up to 15 days by the glypicans released from polymer-coated TNT/Ti implants, indicating their potential application in adjunctive craniosynostosis treatment. Graphical Abstract Titania nanotube- based protein delivery implants have been assessed in vitro to provide a sustained release of bone inhibiting glypicans (rGPC1 and rGPC3). The bioactivity of released glypicans was confirmed by downregulation of BMP2 expression in transfected C2C12 cells. Image 1 Highlights • Titania nanotubes (TNTs) implants have been engineered by electrochemical process. • TNTs glypican releasing implants have been prepared and evaluated. • BMP2 activity was inhibited significantly for up to 15 days by these implants. • The potential for craniosynostosis therapy is proposed by this approach. [ABSTRACT FROM AUTHOR]

This work presents template synthesis of ordered arrays of nickel, cobalt and nickel hexacyanoferrates (NiHCF) with several distinct morphologies such as dots, rods, and tubes. Anodic alumina oxide (AAO) with preferred pore diameters and thickness was fabricated by electrochemical anodization of aluminum used as template. Ni and Co nanostructures inside AAO template were prepared by electrodeposition using galvanostatic method. NiHCF nanostructures were prepared by electrochemical oxidation of Ni using cyclic voltametry (CV) in the presence of hexacyanoferrate ions. The morphology, chemical, and functional properties of prepared nanostructures were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray microscopy (EDAX), and electrochemical methods. The electrocatalytic properties of NiHCF nanorod arrays electrode and their potential for the detection of hydrogen peroxide and biosensing application were demonstrated. [ABSTRACT FROM AUTHOR]

We report the fabrication of highly ordered TiO2 nanotube arrays employing electrochemical anodization of titanium using an organic electrolyte comprised of water, NH4F, and ethylene glycol. To achieve the self-ordering regime of TiO2 nanotube growth and reliable fabrication optimal potential window between 80 and 100 V was determined. We show that anodization voltage can be used not only to control nanotube diameters (70-180 nm) but also to have impact on nanotube growth rate. The anodization voltage and anodization time were used to adjust the length of TiO2 nanotube (thickness of nanotube layer). TiO2 nanotube array films and self-supporting layers with thickness from < 5 μm to > 250 μm were routinely fabricated. [ABSTRACT FROM AUTHOR]

In this paper, we present recent work from our group focussed on the fabrication of nanopore and nanotube arrays using self-ordered electrochemistry, and their application in several key areas including template synthesis, molecular separation, optical sensing, and drug delivery. We have fabricated nanoporous anodic aluminium oxide (AAO) with controlled pore dimensions (20-200nm) and shapes, and used them as templates for the preparation of gold nanorod/nanotube arrays and gold nanotube membranes with characteristic properties such as surface enhanced Raman scattering and selective molecular transport. The application of AAO nanopores as a sensing platform for reflective interferometric detection is demonstrated. Finally, a drug release study on fabricated titania nanotubes confirms their potential for implantable drug delivery applications. [ABSTRACT FROM AUTHOR]

Abstract: Transition metal hexacyanoferrate (MeHCF) have attracted extensive attention because of their outstanding properties including, electrocatalysis, molecular magnetism, biosensing and ion-exchange. This paper describes an approach for fabrication of ordered nanoarrays of Ni hexacyanoferrate (NiHCF) structures with different morphologies such as dots, rods and tubes in order to advance their properties and applications. The method is based on the conversion of Ni into NiHCF nanostructures by electrochemical oxidation in the presence of hexacyanoferrate ions, using nanoporous anodic alumina oxide (AAO) as a template. The structure and morphology of formed Ni and NiHCF nanoarrays were confirmed by scanning electron microscopy (SEM), showing agreement with the pore structures of the AAO template. The electrocatalytic activity of NiHCF nanorod array electrodes showed high catalytic properties for the detection of hydrogen peroxide and the potential to be used as a platform for direct biosensing applications. The ion-exchange ability of fabricated NiHCF nanostructures (nanorods and nanotubes) toward alkali cations such as Na+ has been successfully confirmed. [Copyright &y& Elsevier]

There is considerable interest in combining bioactive polymers such as chitosan with titanium bone implants to promote bone healing and address therapeutic needs. However, the fate of these biodegradable polymers especially on titanium implants is not fully explored. Here we report in situ formation of chitosan microtube (CMT) structures from chitosan films on the implant surface with titania nanotubes (TNTs) layer, based on phosphate buffer-induced transformation and precipitation process. We have comprehensively analyzed this phenomenon and the factors that influence CMT formation, including substrate topography, immersion solution and its pH, effect of coating thickness, and time of immersion. Significance of reported in situ formation of chitosan microtubes on the TNTs surface is possibly to tailor properties of implants with favorable micro and nano morphology using a self-ordering process after the implant's insertion. [ABSTRACT FROM AUTHOR]

Herein, we report on a rational electrochemical approach based on pulse anodization (PA) of aluminum for the fabrication of ultra-short anodic alumina nanotubes (AANTs) with exquisitely controlled dimensions. AANTs with average length 485 ± 180 nm and outer diameter 90 ± 10 nm were fabricated by PA with 0.3 M sulfuric acid and 10% ethanol. Our findings suggest that extensive Joule's heat generation at the nanopore's base is critical for optimized AANTs' liberation from pulse-anodized anodic aluminum oxide (AAO) nanostructure. The heat evolution results in an enhanced oxygen generation and a rapid voltage recovery during PA. While oxygen generation weakens the conjunction between cells, rapid voltage recovery generates asynchronous inner/outer wall structural modulation, which consequently facilitates structural cleavage of nanotubes along mild anodization/hard anodization (MA/HA) interfaces after acid etching. The understanding of AANTs fabrication mechanism enables us for the first time to fabricate ultra-short AANTs by reducing HA duration down to 1 second and using ethanol for enhancing heat generation. The resulting AANTs with controlled dimensions and high liberation yield offer new opportunities for advanced applications such as catalysis, template-assisted nanofabrication, optical sensing and drug delivery. [ABSTRACT FROM AUTHOR]

We report a green approach for synthesis of graphene–carbon nanotube aerogels with three dimensional (3D) interconnected networks prepared from natural graphite rocks. A one-step reaction under the synergic effects of the reduction of graphene oxide (GO) sheets and acid treated carbon nanotubes (CNTs) by ferrous ion is employed eliminating the use of harsh chemicals for the reduction of GO. CNTs are incorporated into the network to increase the robustness and hydrophobicity of aerogels with excellent porosity and oleophilic properties. The prepared aerogels exhibit outstanding adsorption performance for the removal of petroleum products, fats and organic solvents especially under continuous vacuum regime showing adsorption capacity of 28 L of oil per gram of aerogel. The proposed synthetic method is simple and economical for the scalable production of highly porous 3D graphene–carbon nanotube aerogels, which can be successfully used for efficient and cost-effective oil spill clean-up and water purification. [ABSTRACT FROM AUTHOR]

Abstract: This study presents a nanotechnological approach to convert commercially available and non-degradable grocery plastic bags into well-organised carbon nanotube membranes with tuneable molecular transport properties. In this nanotechnological process, plastic bags are used as a carbon source while carbon nanotubes (CNTs) are produced by a catalyst/solvent-free chemical vapour deposition (CVD) approach. Furthermore, CNTs are grown inside nanoporous anodic alumina membranes (NAAMs) featuring hexagonally arranged nanopores, which enable the control over the nanotubes’ organisation and geometry. The transport performance of the resulting CNTs–NAAMs is tested by several dye molecules with positive, negative and neutral charge. These results demonstrate the ability of these membranes to selectively tune molecular transport as a function of the interaction between molecules and inner surface of CNTs. This study proves that an environmentally non-degradable wastematerial as commercial plastic bags can be directly used to produce such sophisticated nanodevices as CNTs membranes. [Copyright &y& Elsevier]

Abstract: This work presents the fabrication of gold nanotube membranes (GNT) using gold deposition on porous anodic aluminum oxide (AAO) template and demonstrates the catalytic properties generated by the nanostructured gold surface. AAO membranes were prepared by electrochemical anodization of Al in 0.3M oxalic acid electrolyte. Electroless gold deposition on AAO was performed via several steps using commercially available gold plating solutions. Scanning electron microscopy (SEM) images confirm that the gold nanotubes formed inside AAO pores have characteristic nanoclustered morphology as a result of the nucleation process during gold deposition. It was found that catalytic properties of GNT membranes depend on the size of gold nanoclusters which can be controlled by pH during nucleation process. The excellent catalytic properties (catalytic rate constant k =0.132min−1) of the GNT membranes were demonstrated by testing catalytic conversion of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) in the presence of NaBH4 as a reductant. The correlation between the size of gold nanoclusters and catalytic activity was verified showing the capability of controlling and further improving catalytic properties of GNT membranes. [Copyright &y& Elsevier]

Abstract: The influence of both nanotube orientation and length on the electrochemical properties of electrodes modified with single-walled carbon nanotubes was investigated. Gold electrodes were modified with either randomly dispersed or vertically aligned nanotubes to which ferrocenemethylamine was attached. Electron transfer kinetics were found to depend strongly on the orientation of the nanotube, with electron transfer between the gold electrode and the ferrocene moiety being 40 times slower through randomly dispersed nanotubes than through vertically aligned nanotubes. The difference is hypothesized to be due to electron transfer being more direct through a single tube than that with electrodes modified with randomly dispersed nanotubes. With the vertically aligned nanotubes the rate constant for electron transfer varied inversely with the mean length of the nanotubes. The results indicate there is an advantage in using aligned carbon nanotube arrays over randomly dispersed nanotubes for achieving efficient electron transfer to bound redox active species such as in the case of bioelectronic or photovoltaic devices. [Copyright &y& Elsevier]