Manganese-containing Bioactive Glass Enhances Osteogenic Activity of TiO2 Nanotube Arrays.

Titanium and its alloys are the most used biomaterials for orthopedic and dental applications. However, up to 10% of these medical devices still fail, mostly due to implant loosening and suboptimal integration at the implant site. The biomaterial surface plays a critical role in promoting osseointegration, which can reduce the risk of device failure. In this study, we propose a novel surface modification on titanium to improve osteogenic differentiation by depositing manganese-containing bioactive glass (BG) on TiO2 nanotube arrays. The surfaces were characterized by scanning electron microscopy, energy dispersive X-ray spectrometer, contact angle goniometry, and X-ray photoelectron spectroscopy. Cell toxicity, viability, adhesion, and proliferation of adipose-derived stem cells on the surfaces were investigated up to 7 days. To evaluate the osteogenic properties of the surfaces, alkaline phosphatase activity, total protein, osteocalcin expression, and calcium deposition were quantified up to 28 days. The results indicate that TiO2 nanotube arrays modified with BG promote cell growth and induce increased osteocalcin and calcium contents when compared to unmodified TiO2 nanotube arrays. The deposition of manganese-containing bioactive glass onto TiO2 nanotubes demonstrates the ability to enhance osteogenic activity on titanium, showing great potential for use in orthopedic and dental implants.

Crystallinity of TiO2 nanotubes and its effects on fibroblast viability, adhesion, and proliferation.

Titanium and titanium alloys are widely used as a biomaterial due to their mechanical strength, corrosion resistance, low elastic modulus, and excellent biocompatibility. TiO2 nanotubes have excellent bioactivity, stimulating the adhesion, proliferation of fibroblasts and adipose-derived stem cells, production of alkaline phosphatase by osteoblasts, platelets activation, growth of neural cells and adhesion, spreading, growth, and differentiation of rat bone marrow mesenchymal stem cells. In this study, we investigated the functionality of fibroblast on titania nanotube layers annealed at different temperatures. The titania nanotube layer was fabricated by potentiostatic anodization of titanium, then annealed at 300, 530, and 630 °C for 5 h. The resulting nanotube layer was characterized using SEM (Scanning Electron Microscopy), TF-XRD (Thin-film X-ray diffraction), and contact angle goniometry. Fibroblasts viability was determined by the CellTiter-Blue method and cytotoxicity by Lactate Dehydrogenase test, and the cell morphology was analyzed by scanning electron microscopy. Also, cell adherence, proliferation, and morphology were analyzed by fluorescence microscopy. The results indicate that the modification in nanotube crystallinity may provide a favorable surface fibroblast growth, especially on substrates annealed at 530 and 630 °C, indicating that these properties provide a favorable template for biomedical implants.

Bactericidal Pectin/Chitosan/Glycerol Films for Food Pack Coatings: A Critical Viewpoint.

Pectin and chitosan films containing glycerol (Gly) at 5, 10, 15, 20, 30, and 40 wt % were prepared in an aqueous HCl solution (0.10 M) by the solvent evaporation method. The unwashed film (UF) containing 40 wt % Gly (UF40) had elongation at break (ε, %) of 19%. Washed films (WFs) had high tensile strength (σ > 46 MPa) and low elongation at break (ε, <5.0%), enabling their use in food packaging applications. The polymers' self-assembling occurred during the washing, increasing the stiffness. The XPS analysis suggests that some HCl is lost during the drying process, resulting in a low acid content on the UF surfaces. The UF40 (at 5.0 mg/mL) exhibits cytocompatibility toward mammalian cells and antimicrobial and anti-adhesive properties against Escherichia coli. The remaining HCl in the UF40 can be a disadvantage for food packaging applications; the UF40 (∅ = 8.5 mm; 55 µm thickness) releases H3O+/HCl, reducing the pH to approximately 3.0 when kept in 200 mL distilled water for approximately 30 min. Therefore, we propose the use of UF40 to coat commercial food packaging. The UF40 has low permeability to water vapor and oxygen and works as a barrier against ultraviolet light. The UF40 is also colorless and completely transparent. The UF40 maintained tomatoes' structural integrity for 18 days at room temperature with no oxidation or microorganism contamination. This paper presents a critical viewpoint concerning chitosan-based films with antimicrobial activities.

Effects of titania nanotube surfaces on osteogenic differentiation of human adipose-derived stem cells.

The surface of an implant is important for successful osseointegration and long-term stability as it can aid in cell migration and proliferation, cell differentiation and allow extracellular matrix production. Earlier studies have shown that nanostructuring the surface of titanium can enhance mesenchymal stem cell (MSC) migration, proliferation, and differentiation. Although many studies have evaluated MSC response on nanostructured surfaces, there are only a few studies that have explored the response of adipose-derived stem cells (ADSC) on titania nanotube surfaces. Because ADSC exhibit great potential in regenerative medicine and have already proven effective in developing new treatments, this study aims to further understand how ADSC interact with titania nanotube surfaces. The results of this study indicate that titania nanotube surfaces enhance ADSC proliferation and differentiation that is also dependent on the size of nanotubes. Additionally, the favorable response of ADSC on nanotube surfaces suggests a potential application in orthopedic tissue regeneration.

Interaction of blood plasma proteins with superhemophobic titania nanotube surfaces.

The need to improve blood biocompatibility of medical devices is urgent. As soon as blood encounters a biomaterial implant, proteins adsorb on its surfaces, often leading to several complications such as thrombosis and failure of the device. Therefore, controlling protein adsorption plays a major role in developing hemocompatible materials. In this study, the interaction of key blood plasma proteins with superhemophobic titania nanotube substrates and the blood clotting responses was investigated. The substrate stability was evaluated and fibrinogen adsorption and thrombin formation from plasma were assessed using ELISA. Whole blood clotting kinetics was also investigated, and Factor XII activation on the substrates was characterized by an in vitro plasma coagulation time assay. The results show that superhemophobic titania nanotubes are stable and considerably decrease surface protein adsorption/Factor XII activation as well as delay the whole blood clotting, and thus can be a promising approach for designing blood contacting medical devices.

Titania (TiO2) nanotube surfaces doped with zinc and strontium for improved cell compatibility.

Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight properties. However, these implants often fail to perform effectively due to poor osseointegration. Nanosurface modification approaches may help to resolve this problem. In this work, TiO2 nanotube (NT) arrays were fabricated on commercially available pure titanium (Ti) surfaces by anodization and annealing. Then, zinc (Zn) and strontium (Sr), important for cell signaling, were doped on the NT surface by hydrothermal treatment. This very simple method of Zn and Sr doping takes less time and energy compared to other complicated techniques. Different surface characterization tools such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), static water contact angle, X-ray diffraction (XRD) and nanoindentation techniques were used to evaluate the modified surfaces. Then, adipose derived stem cells (ADSCs) were cultured with the surfaces to evaluate cell adhesion, proliferation, and growth on the surfaces. After that, the cells were differentiated towards osteogenic lineage to evaluate alkaline phosphatase (ALP) activity, osteocalcin expression, and calcium phosphate mineralization. Results indicate that NT surfaces doped with Zn and Sr had significantly enhanced ADSC adhesion, proliferation, growth, and osteogenic differentiation compared to an unmodified surface, thus confirming the enhanced performance of these surfaces.

Antimicrobial effects of nanofiber poly(caprolactone) tissue scaffolds releasing rifampicin.

This study quantified the antibiotic release kinetics and subsequent bactericidal efficacy of rifampicin (RIF) against Gram-positive and Gram-negative bacteria under in vitro static conditions. Antibiotic-loaded scaffolds were fabricated by electrospinning poly(caprolactone) (PCL) with 10% or 20% (w/w) RIF. Scaffold fiber diameter and RIF loading were characterized, and RIF release kinetics were measured. RIF-releasing and RIF-free scaffolds were inoculated with Pseudomonas aeruginosa and Staphylococcus epidermidis, and the suspended concentration live and dead bacteria were determined by fluorescent microscopy. Adherent bacteria and biofilm formation were examined using scanning electron microscopy. Mean fiber diameters were 557 ± 399 nm for RIF-free, 402 ± 225 nm for 10% RIF, and 665 ± 402 nm for 20% RIF scaffolds. RIF release kinetics exhibited a short-burst release during the first hour, followed by a 7 h, zero-order release during which both RIF scaffolds released ~50% of their initial RIF mass loading. P. aeruginosa and S. epidermidis suspended cell populations proliferated in accordance with logarithmic growth models when exposed to control scaffolds; however both RIF-containing scaffolds completely inhibited bacterial growth in suspension and, subsequently, prevented biofilm formation within the scaffolds through the first 6 h.

Improved hemocompatibility and reduced bacterial adhesion on superhydrophobic titania nanoflower surfaces.

Thrombosis formation and bacterial infection are key challenges for blood-contacting medical devices. When blood components encounter a device's surface, proteins are adsorbed, followed by the adhesion and activation of platelets as well as an immune response. This culminates in clot formation via the trapping of red blood cells in a fibrin matrix, which can block the device's function and cause severe complications for the patient. In addition, bacteria may adhere to a device's surface. This can lead to the formation of a biofilm, a protective layer for bacteria that significantly increases resistance to antibiotics. Despite years of research, no long-term solutions have been discovered to combat these issues. To impede thrombosis, patients often take antiplatelet drugs for the life of their device, which can cause excess bleeding and other complications. Patients can take antibiotics to fight bacterial infection, but these are often ineffective if biofilms are formed. Superhydrophobic surfaces show promise in reducing both thrombosis and bacterial infection on devices by impeding contact between biological components and the biomaterial. In this study, superhydrophobic titania nanoflower surfaces were successfully fabricated on a titanium alloy Ti-6Al-4V substrate with hydrothermal synthesis and vapor-phase silanization. The surface topography, surface wettability, surface chemistry, and surface crystallography of the surfaces was subsequently characterized. Surface hemocompatibility was investigated through lactate dehydrogenase (LDH) cytotoxicity analysis, blood-plasma protein adsorption, platelet and leukocyte adhesion and activation, and whole blood clotting analysis. Surface bacterial infection was characterized through Gram-positive and Gram-negative bacterial adhesion and biofilm morphology. The results indicated a reduction of protein adsorption, platelet and leukocyte adhesion and activation, bacterial adhesion, and biofilm formation as well as improved contact angle stability compared to control surfaces.

Bone morphogenetic protein-2 delivery from polyelectrolyte multilayers enhances osteogenic activity on nanostructured titania.

Incomplete osseointegration is primary cause of failure for orthopedic implants. New biomaterials that present stable signals promoting osteogenesis could reduce failure rates of orthopedic implants. In this study bone morphogenetic protein-2 (BMP-2) was delivered from titania nanotubes (Nt) modified with chitosan/heparin polyelectrolyte multilayers (PEMs). The surfaces were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. BMP-2 release from the surfaces was measured in vitro for up to 28 days. After an initial burst release of BMP-2 during the first 2 days, most of the BMP-2 remained on the surface. To determine the osteogenic properties of these surfaces, they were seeded with rat bone marrow cells; alkaline phosphatase (ALP) activity, total protein, calcium deposition, and osteocalcin were measured up to 4 weeks in vitro. When compared to Nt surfaces, the surfaces with BMP-2 induce greater osteocalcin and calcium deposition. PEMs provide sustained presentation of BMP-2, from a biomimetic surface. This enhances the osteogenic properties of the surface without requiring supraphysiologic growth factor dose. This growth factor delivery strategy could be used to improve bone healing outcomes and reduce complications for recipients of orthopedic implants.

Enhanced blood coagulation and antibacterial activities of carboxymethyl-kappa-carrageenan-containing nanofibers.

Ideal wound dressings should be biocompatible, exhibit high antibacterial activity, and promote blood coagulation. To impart these imperative functions, carboxymethyl-kappa-carrageenan was incorporated into poly(vinyl alcohol) nanofibers (PVA-CMKC). The antibacterial activity of the nanofibers was evaluated. Adsorption of two important blood proteins, fibrinogen and albumin, was also assessed. The adhesion and activation of platelets, and the clotting of whole blood were evaluated to characterize the ability of the nanofibers to promote hemostasis. Adhesion and morphology of both Staphylococcus aureus and Pseudomonas aeruginosa were evaluated using fluorescence microscopy and scanning electron microscopy. CMKC-containing nanofibers demonstrated significant increases in platelet adhesion and activation, percentage of coagulation in whole blood clotting test and fibrinogen adsorption, compared to PVA nanofibers, showing blood coagulation activity. Incorporating CMKC also reduces adhesion and viability of S. aureus and P. aeruginosa bacteria after 24 h of incubation. PVA-CMKC nanofibers show potential application as dressings for wound healing applications.

Biocompatible Crosslinked Nanofibers of Poly(Vinyl Alcohol)/Carboxymethyl-Kappa-Carrageenan Produced by a Green Process.

This study presents a new type of biocompatible nanofiber based on poly(vinyl alcohol) (PVA) and carboxymethyl-kappa-carrageenan (CMKC) blends, produced with no generation of hazardous waste. The nanofibers are produced by electrospinning using PVA:CMKC blends with ratios of 1:0, 1:0.25, 1:0.4, 1:0.5, and 1:0.75 (w/w PVA:CMKC) in aqueous solution, followed by thermal crosslinking. The diameter of the fibers is in the nanometer scale and below 300 nm. Fourier transform infrared spectroscopy shows the presence of the carboxyl and sulfate groups in all the fibers with CMKC. The nanofibers from water-soluble polymers are stabilized by thermal crosslinking. The incorporation of CMKC improves cytocompatibility, biodegradability, cell growth, and cell adhesion, compared to PVA nanofibers. Furthermore, the incorporation of CMKC modulates phenotype of human adipose-derived stem cells (ADSCs). PVA/CMKC nanofibers enhance ADSC response to osteogenic differentiation signals and are therefore good candidates for application in tissue engineering to support stem cells.

Recent trends in natural polysaccharide based bioinks for multiscale 3D printing in tissue regeneration: A review.

Biofabrication by three-dimensional (3D) printing has been an attractive technology in harnessing the possibility to print anatomical shaped native tissues with controlled architecture and resolution. 3D printing offers the possibility to reproduce complex microarchitecture of native tissues by printing live cells in a layer by layer deposition to provide a biomimetic structural environment for tissue formation and host tissue integration. Plant based biomaterials derived from green and sustainable sources have represented to emulate native physicochemical and biological cues in order to direct specific cellular response and formation of new tissues through biomolecular recognition patterns. This comprehensive review aims to analyze and identify the most commonly used plant based bioinks for 3D printing applications. An overview on the role of different plant based biomaterial of terrestrial origin (Starch, Nanocellulose and Pectin) and marine origin (Ulvan, Alginate, Fucoidan, Agarose and Carrageenan) used for 3D printing applications are discussed elaborately. Furthermore, this review will also emphasis in the functional aspects of different 3D printers, appropriate printing material, merits and demerits of numerous plant based bioinks in developing 3D printed tissue-like constructs. Additionally, the underlying potential benefits, limitations and future perspectives of plant based bioinks for tissue engineering (TE) applications are also discussed.

Antimicrobial and cytocompatible chitosan, N,N,N-trimethyl chitosan, and tanfloc-based polyelectrolyte multilayers on gellan gum films.

In this work free-standing gels formed from gellan gum (GG) by solvent evaporation are coated with polysaccharide-based polyelectrolyte multilayers, using the layer-by-layer approach. We show that PEMs composed of iota-carrageenan (CAR) and three different natural polycationic polymers have composition-dependent antimicrobial properties, and support mammalian cell growth. Cationic polymers (chitosan (CHT), N,N,N-trimethyl chitosan (TMC), and an amino-functionalized tannin derivative (TN)) are individually assembled with the anionic iota-carrageenan (CAR) at pH 5.0. PEMs (15-layers) are alternately deposited on the GG film. The GG film and coated GG films with PEMs are characterized by infrared spectroscopy with attenuated total reflectance (FTIR-ATR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and water contact angle (WCA) measurements. The TN/CAR coating provides a hydrophobic (WCA = 127°) and rough surface (Rq = 243 ± 48 nm), and the TMC/CAR coating provides a hydrophilic surface (WCA = 78°) with the lowest roughness (Rq = 97 ± 12 nm). Polymer coatings promote stability and durability of the GG film, and introduce antimicrobial properties against Gram-negative (Salmonella enteritidis) and Gram-positive (Staphylococcus aureus) bacteria. The films are also cytocompatible. Therefore, they have properties that can be further developed as wound dressings and food packaging.

Conformational studies of covalently grafted poly(ethylene glycol) on modified solid matrices using X-ray photoelectron spectroscopy.

Amine functionalized poly(ethylene glycols) (PEGs) with molecular weights 2000 and 4000 Da were covalently grafted onto carboxy modified hydrophilic Sephadex derivatives and hydrophobic polystyrene derivatives using anhydrous amine conjugation methods. Varying PEG surface concentration and layer thickness were achieved by controlling the reaction parameters and were analyzed by X-ray photoelectron spectroscopy (XPS). C-O intensities obtained from high resolution C 1s scans were correlated using the standard overlay model to study the grafting kinetics as well as conformational properties of grafted polymer chains. A detailed and systematic comparison of PEG layer thickness and distance between grafted chains with the Flory radius of surface grafted PEG resulted in valuable information regarding conformational behavior of the polymer. The influence of the nature of the solid matrix on grafting kinetics and conformational properties of the grafted polymer chain was also established from the XPS results.

Carboxymethyl-kappa-carrageenan: A study of biocompatibility, antioxidant and antibacterial activities.

Chemical modification of polysaccharides is an important route to enhance, develop or change polysaccharide properties. In this study, carboxymethylation of kappa-carrageenan (KC) with monochloroacetic acid was performed to achieve different degrees of substitution (DS) of carboxymethyl-kappa-carrageenan (CMKC). The degree of substitution ranged from 0.8 to 1.6 and was calculated from the 1H NMR spectra. The chemical structure of the CMKCs was further characterized by FT-IR, and 13C NMR. FT-IR confirmed the carboxymethylation. Carboxymethylation increased viscosity of KC in water and decreased viscosity of KC in synthetic human sweat. Tests with human adipose derived stem cells showed higher viability and lower cytotoxicity for CMKCs when compared to KC. CMKCs showed no hemolytic activity to human red blood cells. CMKCs have increased antioxidant activity compared to KC. In antibacterial assays, CMKCs with DS of 0.8, 1.0 and 1.2 exhibited growth inhibition against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. CMKC with DS ranging from 1.0 to 1.2 are good candidate biomaterials for cell-contacting applications.

Enhanced hemocompatibility and antibacterial activity on titania nanotubes with tanfloc/heparin polyelectrolyte multilayers.

Biomaterial-associated thrombus formation and bacterial infection remain major challenges for blood-contacting devices. For decades, titanium-based implants have been largely used for different medical applications. However, titanium can neither suppress blood coagulation, nor prevent bacterial infections. To address these challenges, tanfloc/heparin polyelectrolyte multilayers on titania nanotubes array surfaces (NT) were developed. The surfaces were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and water contact angle measurements. To evaluate the hemocompatibility of the surfaces, fibrinogen adsorption, Factor XII activation, and platelet adhesion and activation were analyzed. The antibacterial activity was investigated against Gram-negative P. aeruginosa and Gram-positive S. aureus. Bacterial adhesion and morphology, as well as biofilm formation, were analyzed using fluorescence microscopy and SEM. The anti-thrombogenic properties of the surfaces were demonstrated by significant decreases in fibrinogen adsorption, Factor XII activation, and platelet adhesion and activation. Modifying NT with tanfloc/heparin also reduces the adhesion and proliferation of P. aeruginosa and S. aureus bacteria after 24 hr of incubation, with no biofilm formation. The modified NT surfaces with tanfloc/heparin polyelectrolyte multilayers are a promising biomaterial for use on implant surfaces because of their enhanced blood biocompatibility and antibacterial properties.

Polyelectrolyte multilayers containing a tannin derivative polyphenol improve blood compatibility through interactions with platelets and serum proteins.

To develop hemocompatible surfaces, a cationic tannin derivate (TN) was used to prepare polyelectrolyte multilayers (PEMs) with the glycosaminoglycans heparin (HEP) and chondroitin sulfate (CS). The surface chemistry of the PEMs was characterized using X-ray photoelectron spectroscopy and water contact angle measurements. PEMs assembled with chitosan (CHI) and HEP or CS were used as controls. We investigate the hemocompatibility of PEMs by analyzing the adsorption of key blood serum proteins, adhesion and activation of platelets, and blood clotting kinetics. TN- and CHI-based PEMs adsorb similar amounts of albumin, whereas fibrinogen adsorption was more pronounced on TN-based PEMs, due to strong association with catechol groups. However, TN-based PEMs significantly reduce both platelet adhesion and platelet activation, while CHI-based PEMs promote platelet adhesion and activation. The whole-blood clotting kinetics assay also shows lower blood coagulation on TN-based PEMs. TN is an amphoteric, cationic, condensed tannin derivative with resonance structures. It also contains catechol groups, which are similar to those in mussel adhesive protein. These chemical features enable strong association with fibrinogen, which promotes the platelet-repelling effect. This study provides a new perspective for understanding platelet adhesion and activation on biomaterial surfaces, toward the development of new blood-compatible surfaces using a tannin derivative-based polymer.

Chitosan/gellan gum ratio content into blends modulates the scaffolding capacity of hydrogels on bone mesenchymal stem cells.

Here, we have demonstrated the production and characterization of hydrogel scaffolds based on chitosan/gellan gum (CS/GG) assemblies, without any covalent and metallic crosslinking agents, conventionally used to yield non-soluble polysaccharide-based materials. The polyelectrolyte complexes (physical hydrogels called as PECs) are characterized by Fourier-transform infrared spectroscopy, wide-angle X-ray scattering, and scanning electron microscopy. Hydrogels containing chitosan (CS) excesses (ranging from 60 to 80 wt%) were created. Durable polysaccharide-based scaffolds with structural homogeneity and interconnecting pore networks are developed by modulating the CS/GG weight ratio. The CS/GG hydrogel prepared at 80/20 CS/GG weight ratio (sample CS/GG80-20) is cytocompatible, supporting the attachment, growth, and spreading of bone marrow mesenchymal stem cells (BMSCs) after nine days of cell culture. The cytocompatibility is correlated to the swelling capacity of the PEC in PBS buffer (pH 7.4). By controlling the CS content, we can tune the water uptake of the material, enhancing the capacity to serve as a three-dimensional cell scaffold for BMSCs. This work presents for the first time that CS/GG hydrogels can be applied as scaffolds for tissue engineering purposes.

Poly(vinyl alcohol)/cationic tannin blend films with antioxidant and antimicrobial activities.

This study reports the synthesis, characterization and biological properties of films based on poly(vinyl alcohol) (PVA) and a cationic tannin polymer derivative (TN). Films are obtained from polymeric blends by tuning the PVA/TN weight ratios. The materials are characterized through infrared spectroscopy, X-ray photoelectron spectroscopy, contact angle measurements, mechanical analyses, and scanning electron microscopy. More hydrophilic surfaces are created by modulating the PVA and TN concentrations in the blends. Disintegration tests showed that the films present durability in phosphate buffer (pH 7.4) and low stability in simulated gastric fluid (pH 1.2). The film created at 90/10 PVA/TN weight ratio and crosslinked at 109 PVA/glutaraldehyde molar ratio (sample PVA10/TN10) supports the attachment and proliferation of bone marrow mesenchymal stem cells after 7 days of culture. The scaffolding capacity of the PVA10/TN10 surface is compared with titanium, one of the most important biomedical materials used in bone replacements. Also, the PVA/TN films exhibited cytocompatibility, antioxidant and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. These properties make PVA/TN films are candidates for biomedical applications in the tissue engineering field.

Nanostructured tantala as a template for enhanced osseointegration.

The goal of current dental and orthopedic biomaterials research is to design implants that induce controlled and guided tissue growth, and rapid healing. In addition to acceleration of normal wound healing phenomena, these implants should result in the formation of a characteristic interfacial layer with adequate biomechanical properties. To achieve these goals, however, a better understanding of events at the bone-material interface is needed, as well as the development of new materials and approaches that promote osseointegration. Here we present novel nanostructured nanoarrays from tantala that can promote cell adhesion and differentiation. Our results suggest that tantala nanotube arrays enhance osteoblast cell adhesion, proliferation and differentiation. The routes of fabrication of tantala nanotube arrays are flexible and cost-effective, enabling realization of desired platform topologies on existing non-planar orthopedic implants.