Nanoceria as Antioxidant: Synthesis and Biomedical Applications.

The therapeutic application of nanomaterials has been a focus of numerous studies in the past decade. Due to its unique redox properties, cerium oxide (ceria) is finding widespread use in the treatment of medical disorders caused by the reactive oxygen intermediates (ROI). The radical-scavenging role of ceria nanoparticles (nanoceria) have been established, as well as the autocatalytic ability of nanoceria to regenerate under various environmental conditions. The synthesis of nanoceria in biocompatible media has also been reported along with cell viability in order to determine the potential use of nanoceria in biomedical applications.

Laser microfabrication of hydroxyapatite-osteoblast-like cell composites.

We have developed a novel approach for layer-by-layer growth of tissue-engineered materials using a direct writing process known as matrix assisted pulsed laser evaporation direct write (MAPLE DW). Unlike conventional cell-seeding methods, this technique provides the possibility for cell-material integration prior to artificial tissue fabrication. This process also provides greater flexibility in selection and processing of scaffold materials. In addition, MAPLE DW offers rapid computer-controlled deposition of mesoscopic voxels at high spatial resolutions. We have examined MAPLE DW processing of zirconia and hydroxyapatite scaffold materials that can provide a medical device with nearly inert and bioactive implant-tissue interfaces, respectively. We have also demonstrated codeposition of hydroxyapatite, MG 63 osteoblast-like cells, and extracellular matrix using MAPLE DW. We have shown that osteoblast-like cells remain viable and retain the capacity for proliferation when codeposited with bioceramic scaffold materials. Our results on MG 63-hydroxyapatite composites can be extended to develop other integrated cell-scaffold structures for medical and dental applications.

Nanostructured GaN nucleation layer for light-emitting diodes.

This paper addresses the formation of nanostructured gallium nitride nucleation (NL) or initial layer (IL), which is necessary to obtain a smooth surface morphology and reduce defects in h-GaN layers for light-emitting diodes and lasers. From detailed X-ray and HR-TEM studies, researchers determined that this layer consists of nanostructured grains with average grain size of 25 nm, which are separated by small-angle grain boundaries (with misorientation approximately 1 degrees), known as subgrain boundaries. Thus NL is considered to be single-crystal layer with mosaicity of about 1 degrees. These nc grains are mostly faulted cubic GaN (c-GaN) and a small fraction of unfaulted c-GaN. This unfaulted Zinc-blende c-GaN, which is considered a nonequilibrium phase, often appears as embedded or occluded within the faulted c-GaN. The NL layer contained in-plane tensile strain, presumably arising from defects due to island coalescence during Volmer-Weber growth. The 10L X-ray scans showed c-GaN fraction to be over 63% and the rest h-GaN. The NL layer grows epitaxially with the (0001) sapphire substrate by domain matching epitaxy, and this epitaxial relationship is remarkably maintained when c-GaN converts into h-GaN during high-temperature growth.

Biological properties of carbon nanotubes.

Carbon nanotubes are novel materials with unique physical and chemical properties, and have been considered for use in numerous technological applications. More recently, attention has turned to the unique biological and medical properties of these materials. In this review, the processing, chemical properties, physical properties, nucleic acid interaction, cell interaction, and toxicologic properties of nanotubes are described. Finally, future directions in this area are discussed.

Two photon induced polymerization of organic-inorganic hybrid biomaterials for microstructured medical devices.

Three-dimensional microstructured medical devices, including microneedles and tissue engineering scaffolds, were fabricated by two photon induced polymerization of Ormocer organic-inorganic hybrid materials. Femtosecond laser pulses from a titanium:sapphire laser were used to break chemical bonds on Irgacure 369 photoinitiator within a small focal volume. The radicalized starter molecules reacted with Ormocer US-S4 monomers to create radicalized polymolecules. The desired structures are fabricated by moving the laser focus in three dimensions using a galvano-scanner and a micropositioning system. Ormocer surfaces fabricated using two photon induced polymerization demonstrated acceptable cell viability and cell growth profiles against B35 neuroblast-like cells and HT1080 epithelial-like cells. Lego-like interlocking tissue engineering scaffolds and microneedle arrays with unique geometries were created using two photon induced polymerization. These results suggest that two photon induced polymerization is able to create medical microdevices with a larger range of sizes, shapes, and materials than chemical isotropic etching, injection molding, reactive ion etching, surface micromachining, bulk micromachining, polysilicon micromolding, lithography-electroforming-replication, or other conventional microfabrication techniques.

Three-dimensional direct writing of B35 neuronal cells.

We have demonstrated two-dimensional and three-dimensional transfer of B35 neuronal cells onto and within polymerized Matrigel substrates, using matrix-assisted pulsed laser evaporation-direct write (MDW). The B35 cells were transferred from a quartz ribbon to depths of up to 75 microm by systematically varying the fluence emitted from the ArF (lambda = 193 nm) laser source. MDW-transferred cells were examined using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), 4',6-diamidino-2-phenylindole (DAPI), and alpha-tubulin staining. Confocal microscopy has shown that the transferred B35 cells extended their axons outward in three dimensions within the polymerized Matrigel substrate. The B35 cells made axonal connections and formed a three-dimensional neural network within 72 h after MDW transfer. In addition, TUNEL staining demonstrated that only 3% of the B35 cells underwent apoptosis after being transferred using the MDW process. MDW and other emergent direct write processes may provide unique approaches for creating layered, heterogeneous, three-dimensional cell-seeded scaffolds for use in peripheral nerve repair.

Defect mediated photocatalytic decomposition of 4-chlorophenol on epitaxial rutile thin films under visible and UV illumination.

We show that pure rutile TiO(2) can be photo-responsive even under low energy visible light after annealing in vacuum where we envisage that the point defects, i.e. oxygen vacancies and titanium interstitials, serve an important role. In this study, single crystal rutile films were grown by the pulsed laser deposition technique and then vacuum annealed under different oxygen pressures to introduce defects into their lattices. 4-chlorophenol was selected as a model material and decomposed by the annealed TiO(2) films where the maximum photocatalytic reaction rate constants were determined as 0.0107 and 0.0072 min(-1) under UV and visible illumination. Epitaxial growth along the [200] direction was confirmed by φ-scan and 2θ-scan XRD and the epitaxial relationship between the rutile film and the c-sapphire substrate was explained as (100)[010](R) [parallel] (0001)[12[combining overline]10](S). The formation of atomically sharp interfaces and the epitaxial growth were ascertained by annular dark-field STEM imaging. Based on the XPS, UV-vis and PL spectroscopy results, it was found that the defect concentration increased after annealing under lower pressures, e.g. 5 × 10(-6) Torr. In contrast, more perfect crystals were obtained when the films were annealed under high oxygen pressures, namely 5 × 10(1) Torr. The morphology of the films was also investigated by employing an AFM technique. It was observed that increase of the annealing pressure results in the formation of larger grains. It was also found that the electrical resistivity of the rutile films strongly increased by about three orders of magnitude when the annealing pressure increased from 5 × 10(-4) to 5 × 10(1) Torr.

Laser ablation imparts controlled micro-scale pores in electrospun scaffolds for tissue engineering applications.

Electrospun scaffolds have been used extensively for tissue engineering applications due to the simple processing scheme and versatility. However, many additional benefits can be imparted to these materials via post-processing techniques. Specifically the addition of structured pores on the micro-scale can offer a method to enable patterned cell adhesion, enhanced diffusional properties, and/or guide vascular infiltration upon implantation in vivo. In this study, we laser ablated electrospun poly(L: -lactic acid) (PLA) scaffolds and assessed the ablation process and cellular interaction by examining human adipose-derived stem cell (hASC) viability and proliferation on laser micro-machined scaffolds. Laser ablated pores of 150, 300, and 600 µm diameter were micro-machined through electrospun PLA scaffolds. Laser ablation parameters were varied and it was determined that the aperture and z-travel direction of the laser linearly correlated with the ablated pore diameter. To assess cytocompatibility of the micro-machined scaffolds, hASCs were seeded on each scaffold and cell viability was assessed on day 7. Human ASCs were able to adhere around the micro-machined features. DNA content was quantified on all scaffolds and it was determined that hASCs were able to proliferate on all scaffolds. The process of laser ablation could impart many beneficial features to electrospun scaffolds by increasing mass transport and mimicking micro-scale features and assisting in patterning of cells around micro-machined features.

Modification of microneedles using inkjet printing.

In this study, biodegradable acid anhydride copolymer microneedles containing quantum dots were fabricated by means of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing. Nanoindentation was performed to obtain the hardness and the Young's modulus of the biodegradable acid anhydride copolymer. Imaging of quantum dots within porcine skin was accomplished by means of multiphoton microscopy. Our results suggest that the combination of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing enables fabrication of solid biodegradable microneedles with a wide range of geometries as well as a wide range of pharmacologic agent compositions.

Electrospun composite poly(L-lactic acid)/tricalcium phosphate scaffolds induce proliferation and osteogenic differentiation of human adipose-derived stem cells.

Development of tissue-engineered bone constructs has recently focused on the use of electrospun composite scaffolds seeded with stem cells from various source tissues. In this study, we fabricated electrospun composite scaffolds consisting of beta-tricalcium phosphate (TCP) crystals and poly(L-lactic acid) (PLA) at varying loading levels of TCP (0, 5, 10, 20 wt%) and assessed the composite scaffolds' material properties and ability to induce proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in the presence of osteogenic differentiating medium. The electrospun scaffolds all exhibited a nonwoven structure with an interconnected porous network. With the addition of TCP, the fiber diameter increased with each treatment ranging from 503.39 +/- 20.31 nm for 0 wt% TCP to 1267.36 +/- 59.03 nm for 20 wt% TCP. Tensile properties of the composite scaffolds were assessed and the overall tensile strength of the neat scaffold (0 wt% TCP) was 847 +/- 89.43 kPA; the addition of TCP significantly decreased this value to an average of 350.83 +/- 38.57 kPa. As the electrospun composite scaffolds degraded in vitro, TCP was released into the medium with the largest release occurring within the first 6 days. Human ASCs were able to adhere, proliferate and osteogenically differentiate on all scaffold combinations. DNA content increased in a temporal manner for each scaffold over 18 days in culture although for the day 12 timepoint, the 10 wt% TCP scaffold induced the greatest hASC proliferation. Endogenous alkaline phosphatase activity was enhanced on the composite PLA/TCP scaffolds compared to the PLA control particularly by day 18. It was noted that at the highest TCP loading levels of 10 and 20 wt%, there was a dramatic increase in the amount of cell-mediated mineralization compared to the 5 wt% TCP and the neat PLA scaffold. This work suggests that local environment cues provided by the biochemical nature of the scaffold can accelerate the overall osteogenic differentiation of hASCs and encourage rapid ossification.

Pulsed laser deposition of antimicrobial silver coating on Ormocer microneedles.

One promising option for transdermal delivery of protein- and nucleic acid-based pharmacologic agents involves the use of microneedles. However, microneedle-generated pores may allow microorganisms to penetrate the stratum corneum layer of the epidermis and cause local or systemic infection. In this study, microneedles with antimicrobial functionality were fabricated using two-photon polymerization-micromolding and pulsed laser deposition.The antibacterial activity of the silver-coated organically modified ceramic (Ormocer)microneedles was demonstrated using an agar diffusion assay. Human epidermal keratinocyte viability on the Ormocer surfaces coated with silver was similar to that on uncoated Ormocer surfaces. This study indicates that coating microneedles with silver thin films using pulsed laser deposition is a useful and novel approach for creating microneedles with antimicrobial functionality.