Nanoscale Surface Modifications Research Articles

Enhancing the osteoblastic differentiation through nanoscale surface modifications.

Human mesenchymal stem cells (MSCs) showed larger differentiation into osteoblasts on nanoscale amorphous titanium oxide (TiO2 ) coatings in comparison to polycrystalline TiO2 coatings or native oxide layers. In this article, we showed that the subtle alterations in the surface properties due to a different atomic ordering of titanium oxide layers could substantially modify the osteoblastic differentiation of MSCs. Amorphous (a) and polycrystalline (c) TiO2 coatings were deposited on smooth (PT) and microstructured sandblasted/acid-etched (SLA) Ti substrates using a magnetron sputtering system. The surface roughness, water contact angle, structure, and composition were measured using confocal microscopy, drop sessile drop, X-ray diffraction, and X-ray photoelectron spectroscopy, respectively. The ∼70-nm-thick coatings presented a well-passivated and uniform TiO2 (Ti4+ ) surface composition, while the substrates (native oxide layer) showed the presence of Ti atoms in lower valence states. The polycrystalline TiO2 -coated surfaces (cPT and cSLA) showed the same cell attachment as the uncoated metallic surfaces (PT and SLA), and in both cases, it was lower on the rough than on the smooth surfaces. However, attachment and differentiation were significantly increased on the amorphous TiO2 -coated surfaces (aPT and aSLA). The amorphous coated Ti surfaces presented the highest expression of integrins and production of osteogenic proteins in comparison to the uncoated and crystalline-coated Ti surfaces. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 498-509, 2017.

Bone Tissue Engineering: Nanomedicine Approaches

Tissue engineering focuses on the use of cellular and material-based therapies aimed at targeted tissue regeneration caused by traumatic, degenerative, and genetic disorders. Current treatments for bone injuries and defects that will not spontaneously heal employ replacement rather than regeneration, which is accompanied by long-term complications. In this chapter, attention is focused on state-of-the-art research techniques and materials that are aimed at alleviating these complications by inducing bone-healing rather than bone-substitution; specifically, the use of nanoscale materials and surface modifications in order to closely mimic the microenvironment of bone. Today, these nanoscale technologies are coming to the forefront in medicine because of their biocompatibility, tissue-specificity, and integration and ability to act as therapeutic carriers. Keywords: bone tissue engineering; nanomedicine; regenerative medicine; biomaterials; surface modification

Controlled implant/soft tissue interaction by nanoscale surface modifications of 3D porous titanium implants.

Porous titanium implants are widely employed in the orthopaedics field to ensure good bone fixation. Recently, the use of porous titanium implants has also been investigated in artificial larynx development in a clinical setting. Such uses necessitate a better understanding of the interaction of soft tissues with porous titanium structures. Moreover, surface treatments of titanium have been generally evaluated in planar structures, while the porous titanium implants have complex 3 dimensional (3D) architectures. In this study, the determining factors for soft tissue integration of 3D porous titanium implants were investigated as a function of surface treatments via quantification of the interaction of serum proteins and cells with single titanium microbeads (300-500 μm in diameter). Samples were either acid etched or nanostructured by anodization. When the samples are used in 3D configuration (porous titanium discs of 2 mm thickness) in vivo (in subcutis of rats for 2 weeks), a better integration was observed for both anodized and acid etched samples compared to the non-treated implants. If the implants were also pre-treated with rat serum before implantation, the integration was further facilitated. In order to understand the underlying reasons for this effect, human fibroblast cell culture tests under several conditions (directly on beads, beads in suspension, beads encapsulated in gelatin hydrogels) were conducted to mimic the different interactions of cells with Ti implants in vivo. Physical characterization showed that surface treatments increased hydrophilicity, protein adsorption and roughness. Surface treatments also resulted in improved adsorption of serum albumin which in turn facilitated the adsorption of other proteins such as apolipoprotein as quantified by protein sequencing. The cellular response to the beads showed considerable difference with respect to the cell culture configuration. When the titanium microbeads were entrapped in cell-laden gelatin hydrogels, significantly more cells migrated towards the acid etched beads. In conclusion, the nanoscale surface treatment of 3D porous titanium structures can modulate in vivo integration by the accumulative effect of the surface treatment on several physical factors such as protein adsorption, surface hydrophilicity and surface roughness. The improved protein adsorption capacity of the treated implants can be further exploited by a pre-treatment with autologous serum to render the implant surface more bioactive. Titanium microbeads are a good model system to observe these effects in a 3D microenvironment and provide a better representation of cellular responses in 3D.

A systematic study of pool boiling heat transfer on structured porous surfaces: From nanoscale through microscale to macroscale

An experimental study has been conducted to examine the effects of macroscale, microscale, and nanoscale surface modifications in water pool boiling heat transfer and to determine the different heat transfer enhancing mechanisms at different scales. Nanostructured surfaces are created by acid etching, while microscale and macroscale structured surfaces are synthesized through a sintering process. Six structures are studied as individual and collectively integrated surfaces from nanoscale through microscale to macroscale: polished plain, flat nanostructured, flat porous, modulated porous, nanostructured flat porous, and nanostructured modulated porous. Boiling performance is measured in terms of critical heat flux (CHF) and heat transfer coefficient (HTC). Both HTC and CHF have been greatly improved on all modified surfaces compared to the polished baseline. Hierarchical multiscale surfaces of integrated nanoscale, microscale, and macroscale structures have been proven to have the most significant improvements on HTC and CHF. The CHF and HTC of the hierarchical multiscale modulated porous surface have achieved the most significant improvements of 350% and 200% over the polished plain surface, respectively. Experimental results are compared to the predictions of a variety of theoretical models with an attempt to reveal the different heat transfer enhancing mechanisms at different scales. It is concluded that models for the structured surfaces at all scales need to be further developed to be able to have good quantitative predictions of CHFs on structured surfaces.

Nanometer-scale features on micrometer-scale surface texturing: A bone histological, gene expression, and nanomechanical study

Micro- and nanoscale surface modifications have been the focus of multiple studies in the pursuit of accelerating bone apposition or osseointegration at the implant surface. Here, we evaluated histological and nanomechanical properties, and gene expression, for a microblasted surface presenting nanometer-scale texture within a micrometer-scale texture (MB) (Ossean™ Surface, Intra-Lock International, Boca Raton, FL) versus a dual-acid etched surface presenting texture at the micrometer-scale only (AA), in a rodent femur model for 1, 2, 4, and 8weeks in vivo. Following animal sacrifice, samples were evaluated in terms of histomorphometry, biomechanical properties through nanoindentation, and gene expression by real-time quantitative reverse transcription polymerase chain reaction analysis. Although the histomorphometric, and gene expression analysis results were not significantly different between MB and AA at 4 and 8weeks, significant differences were seen at 1 and 2weeks. The expression of the genes encoding collagen type I (COL-1), and osteopontin (OPN) was significantly higher for MB than for AA at 1week, indicating up-regulated osteoprogenitor and osteoblast differentiation. At 2weeks, significantly up-regulated expression of the genes for COL-1, runt-related transcription factor 2 (RUNX-2), osterix, and osteocalcin (OCN) indicated progressive mineralization in newly formed bone. The nanomechanical properties tested by the nanoindentation presented significantly higher-rank hardness and elastic modulus for the MB compared to AA at all time points tested. In conclusion, the nanotopographical featured surfaces presented an overall higher host-to-implant response compared to the microtextured only surfaces. The statistical differences observed in some of the osteogenic gene expression between the two groups may shed some insight into the role of surface texture and its extent in the observed bone healing mechanisms.

Nano-structuring of CaF2 surfaces by slow highly charged ions: simulation and experiment

The impact of individual slow highly charged ions (HCI) on insulators can create nano-scale surface modifications. We present recent experimental results on nano-hillock and etch pit formation on CaF2, where the appearance of surface modifications is observed only above a threshold projectile potential and kinetic energy depending on the type of damage. A proof-of-principle molecular dynamics simulation offers insights into the early stages of damage formation.

Nanoscale Surface Modifications by Magnetic Field-Assisted Finishing

A magnetic field-assisted finishing (MAF) process has been developed to reduce the sidewall surface roughness of the 5–20 μm wide curvilinear pores of microelectromechanical systems micropore X-ray optics to <1 nm Rq. Although the feasibility of this process has been demonstrated on these optics, a clear understanding of the MAF process' material removal mechanisms has not been attained. In an attempt to discover these mechanisms, the MAF process is applied to a flat workpiece, allowing for direct observation and tracking of changes to distinctive surface features before and after MAF. Atomic force microscopy, field-emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy are used to analyze the surface morphology and composition with respect to finishing time. These observations suggest that the MAF process modified the surface, reducing surface roughness (from 0.8 nm to 0.6 nm Rz on silicon) by removing relatively low-wavelength surface features. Moreover, the MAF process appears to modify the surface mechanically.

Gene Expression Profiling and Histomorphometric Analyses of The Early Bone Healing Response Around Nanotextured Implants

While in vitro studies have shown that nanoscale surface modifications influence cell fate and activity, there is little information on how they modulate healing at the bone-implant interface. This study aims to investigate the effect of nanotopography at early time intervals when critical events for implant integration occur. Untreated and sulfuric acid/hydrogen peroxide-treated machined-surface titanium alloy implants were placed in rat tibiae. Samples were processed for DNA microarray analysis and histomorphometry. At both 3 and 5 days, the gene expression profile of the healing tissue around nanotextured implants differed from that around machined-surface implants or control empty holes, and were accompanied by an increase in bone-implant contact on day 5. While some standard pathways such as the immune response predominated, a number of unclassified genes were also implicated. Nanotexture elicits an initial gene response that is more complex than suspected so far and favors healing at the bone-implant interface.

Eluting combination drugs from stents

Cardiovascular diseases (CVD) are one of the leading causes of death across the globe. Pathogenesis of coronary artery disease (CAD) is lead by the progression of atherosclerotic lacerations in coronary arteries. Percutaneous coronary intervention (PCI) using balloon angioplasty was introduced in 1979 and was majorly used in the treatment of these lesions. Introduction of bare metal stents (BMS) has revolutionized stenting procedures overcoming elastic recoil and reducing restenosis commonly associated with balloon angioplasty, but follow up studies have shown 20-30% prevalence of in-stent restenosis (ISR), this led to the development of drug eluting stents (DES). But long-term follow up studies have shown increased liability of stent thrombosis. Boosting the development of safer and effective DES expounding for therapies like biodegradable polymer based DES, polymer free DES, bioresorbable DES and combination DES to collectively reduce neointimal hyperplasia and promote endothelial healing. In dual-DES development, a combination employing an anti-restenotic agent (for preventing VSMC's proliferation), which is released for the first few weeks, and then the second drug a pro-healing agent (promoting re-endothelialization) released after a month would be ideal. Growing understanding in the areas of polymer therapeutics, nanoscale surface modifications and gene therapy would assist in the delivery of multiple drugs, which would further help in the design of promising therapeutic strategies for the treatment of CAD using stent based therapies.

Phase Diagram for NanostructuringCaF2Surfaces by Slow Highly Charged Ions

The impact of individual slow highly charged ions (HCI) on alkaline earth halide and alkali halide surfaces creates nano-scale surface modifications. For different materials and impact energies a wide variety of topographic alterations have been observed, ranging from regularly shaped pits to nanohillocks. We present experimental evidence for the creation of thermodynamically stable defect agglomerations initially hidden after irradiation but becoming visible as pits upon subsequent etching. A well defined threshold separating regions with and without etch-pit formation is found as a function of potential and kinetic energies of the projectile. Combining this novel type of surface defects with the previously identified hillock formation, a phase diagram for HCI induced surface restructuring emerges. The simulation of the energy deposition by the HCI in the crystal provides insight into the early stages of the dynamics of the surface modification and its dependence on the kinetic and potential energies.

Nanoscale surface modifications to control capillary flow characteristics in PMMA microfluidic devices

Polymethylmethacrylate (PMMA) microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC) film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization) through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices.

Nanoscale surface modifications and formation of conical structures at aluminum surface induced by single shot exposure of soft x-ray laser pulse

We irradiated the soft x-ray laser (SXRL) pulses having a wavelength of 13.9 nm, a duration time of 7 ps, and fluences of up to 27 mJ/cm2 to aluminum (Al) surface. After the irradiation process, the modified surface was observed with the visible microscope, the scanning electron microscope, and the atomic force microscope. The surface modifications caused by the SXRL pulses were clearly seen, and it was found that the conical structures having about 70–150 nm in diameters were formed under a single pulse shot. The conical structures were formed in the features with the average depth of about 40 nm, and this value was in accordance with the attenuation length of the SXRL beam for Al. However, those conical structures were deconstructed under the multiple pulse shots exposure. Thermomechanical modeling of SXRL laser interaction with Al surface, which explains nanostructure surface modification, was provided.

Nanoscale surface modifications of medically relevant metals: state-of-the art and perspectives.

Evidence that nanoscale surface properties stimulate and guide various molecular and biological processes at the implant/tissue interface is fostering a new trend in designing implantable metals. Cutting-edge expertise and techniques drawn from widely separated fields, such as nanotechnology, materials engineering and biology, have been advantageously exploited to nanoengineer surfaces in ways that control and direct these processes in predictable manners. In this review, we present and discuss the state-of-the-art of nanotechnology-based approaches currently adopted to modify the surface of metals used for orthopedic and dental applications, and also briefly consider their use in the cardiovascular field. The effects of nanoengineered surfaces on various in vitro molecular and cellular events are firstly discussed. This review also provides an overview of in vivo and clinical studies with nanostructured metallic implants, and addresses the potential influence of nanotopography on biomechanical events at interfaces. Ultimately, the objective of this work is to give the readership a comprehensive picture of the current advances, future developments and challenges in the application of the infinitesimally small to biomedical surface science. We believe that an integrated understanding of the in vitro and particularly of the in vivo behavior is mandatory for the proper exploitation of nanostructured implantable metals and, indeed, of all biomaterials.

Nanostripe patterning of glass surface by nanoimprint using self-organized oxide mold

We investigated nanoscale surface modifications of silicate glass plates by applying a thermal nanoimprint technique, in which self-organized nanopattern molds of sapphire (α-Al 2O 3 single crystal) wafer were used. Nanopatterns of the sapphire mold exhibited regularly arranged straight atomic-steps with a uniform height of 0.2 nm and atomically flat terraces about 80 nm in width. We succeeded in forming subnanometer-stepped surfaces of glass. By pressing the glass plate over the mold and then slowly cooling (3 °C/min), a three-dimensional nanostriped pattern (periodic distance of 60–85 nm and peak-to-valley height of 8 nm) was obtained on the glass plate. Softening behavior of the nanopatterned glass morphology was observed at temperatures about 20 °C lower than the glass transition temperature of the bulk glass. The Vickers hardness of the nanostriped glass was estimated to be higher than that of non-patterned glass, and the surface of the nanostriped glass was more hydrophobic than that of non-patterned glass.

Slow highly charged ions for nanoscale surface modifications

With the Dresden EBIT (electron beam ion trap) a room temperature, compact and long-term stable source of slow highly charged ions (HCIs) has been developed and prepared for small series production. A wide spectrum of ions such as Ar 18+, Fe 24+ and Xe 44+ have been produced and extracted with energies less than q×10 keV ( q – ion charge). At ion–surface interactions the high neutralization energy of the ionic projectiles leads to high power densities of 10 12–10 13 W/cm 2 at the surface. Thus, these ions can produce nanoscale material modifications and can be used for surface analysis techniques as well. Examples of extracted and magnetically analyzed ion beams are given. Fields of applications of slow highly charged ions are summarized.

Scanning tunneling nanolithography of amorphous GeSb2Te4 films

Nanoscale surface modifications have been induced using a scanning tunneling microscope in a chalcogenide film GeSb2Te4, which is employed for optical phase change memories. Depressions and expansions appear when the surface is scanned with positive and negative tip voltages under relative humidity higher than ∼50%. It is plausible that the depression and the expansion are produced through electrochemical reactions and anodic oxidation processes.