Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin : evaluation in a rat segmental defect model

Objective To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 μg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.

Multiphasic construct studied in an ectopic osteochondral defect model

In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials.

On natures of sub-gap photoelectric and optical spectra in nitrogen-contaminated nanocrystalline diamond

Experimentally observed optical and photoelectrical spectra of nitrogen-contaminated (unintentionally doped) nano-crystalline CVD diamond films are simulated using semi-empirical adiabatic General Skettrup Model (GSM), which presumes dominant contributions of defect states from sp 3-coordinated intra-granular carbon atoms to intra-band single electron spectrum N(E) of the material. This picture disagrees with a common viewpoint that the N(E) spectrum of the gap states in diamond powders and polycrystalline CVD films mainly originates from π and π* bonds of sp2-coordinated carbon atoms, which are distributed nearly uniformly over outer surfaces and/or interfaces of the diamond grains. The GSM predicts as well strong effect of granular morphology on the density of intra-band defect states in polycrystalline diamonds.

Nano-scale morphology and electron spectrum of defect states in low-k SiOCH films

Results of experimental investigations on the relationship between nanoscale morphology of carbon doped hydrogenated silicon-oxide (SiOCH) low-k films and their electron spectrum of defect states are presented. The SiOCH films have been deposited using trimethylsilane (3MS) - oxygen mixture in a 13.56 MHz plasma enhanced chemical vapor deposition (PECVD) system at variable RF power densities (from 1.3 to 2.6 W/cm2) and gas pressures of 3, 4, and 5 Torr. The atomic structure of the SiOCH films is a mixture of amorphous-nanocrystalline SiO2-like and SiC-like phases. Results of the FTIR spectroscopy and atomic force microscopy suggest that the volume fraction of the SiC-like phase increases from ∼0.2 to 0.4 with RF power. The average size of the nanoscale surface morphology elements of the SiO2-like matrix can be controlled by the RF power density and source gas flow rates. Electron density of the defect states N(E) of the SiOCH films has been investigated with the DLTS technique in the energy range up to 0.6 eV from the bottom of the conduction band. Distinct N(E) peaks at 0.25 - 0.35 eV and 0.42 - 0.52 eV below the conduction band bottom have been observed. The first N(E) peak is identified as originated from E1-like centers in the SiC-like phase. The volume density of the defects can vary from 1011 - 1017 cm-3 depending on specific conditions of the PECVD process.

A kinetic model for an argon plasma containing dust grains

A complex low-pressure argon discharge plasma containing dust grains is studied using a Boltzmann equation for the electrons and fluid equations for the ions. Local effects, such as the spatial distribution of the dust density and external electric field, are included, and their effect on the electron energy distribution, the electron and ion number densities, the electron temperature, and the dust charge are investigated. It is found that dust particles can strongly affect the plasma parameters by modifying the electron energy distribution, the electron temperature, the creation and loss of plasma particles, as well as the spatial distributions of the electrons and ions. In particular, for sufficiently high grain density and/or size, in a low-pressure argon glow discharge, the Druyvesteyn-like electron distribution in pristine plasmas can become nearly Maxwellian. Electron collection by the dust grains is the main cause for the change in the electron distribution function.

Defect healing and enhanced nucleation of carbon nanotubes by low-energy ion bombardment

Structural defects inevitably appear during the nucleation event that determines the structure and properties of single-walled carbon nanotubes. By combining ion bombardment experiments with atomistic simulations we reveal that ion bombardment in a suitable energy range allows these defects to be healed resulting in an enhanced nucleation of the carbon nanotube cap. The enhanced growth of the nanotube cap is explained by a nonthermal ion-induced graphene network restructuring mechanism.

Reducing bubble defect on the outsole production process in the footwear manufacturing industry

The purpose of this study is to discover the significant factors causing the bubble defect on the outsoles manufactured by the Case Company. The bubble defect occurs approximately 1.5 per cent of the time or in 36 pairs per day. To understand this problem, experimental studies are undertaken to identify various factors such as injector temperature, mould temperature; that affects the production of waste. The work presented in this paper comprises a review of the relevant literature on the Six Sigma DMAIC improvement process, quality control tools, and the design of the experiments. After the experimentation following the Six Sigma process, the results showed that the defect occurred in approximately 0.5 per cent of the products or in 12 pairs per day; this decreased the production cost from 6,120 AUD per month to 2,040 AUD per month. This research aimed to reduce the amount of waste in men’s flat outsoles. Hence, the outcome of research presented in this paper should be used as a guide for applying the appropriate process for each type of outsole.

Low delta18O zircon grains in the Neoarchean Rum Jungle Complex, northern Australia: An indicator of emergent continental crust

The timing of widespread continental emergence is generally considered to have had a dramatic effect on the hydrological cycle, atmospheric conditions, and climate. New secondary ion mass spectrometry (SIMS) oxygen and laser-ablation–multicollector–inductively coupled plasma–mass spectrometry (LA-MC-ICP-MS) Lu-Hf isotopic results from dated zircon grains in the granitic Neoarchean Rum Jungle Complex provide a minimum time constraint on the emergence of continental crust above sea level for the North Australian craton. A 2535 ± 7 Ma monzogranite is characterized by magmatic zircon with slightly elevated δ18O (6.0‰–7.5‰ relative to Vienna standard mean ocean water [VSMOW]), consistent with some contribution to the magma from reworked supracrustal material. A supracrustal contribution to magma genesis is supported by the presence of metasedimentary rock enclaves, a large population of inherited zircon grains, and subchondritic zircon Hf (εHf = −6.6 to −4.1). A separate, distinct crustal source to the same magma is indicated by inherited zircon grains that are dominated by low δ18O values (2.5‰–4.8‰, n = 9 of 15) across a range of ages (3536–2598 Ma; εHf = −18.2 to +0.4). The low δ18O grains may be the product of one of two processes: (1) grain-scale diffusion of oxygen in zircon by exchange with a low δ18O magma or (2) several episodes of magmatic reworking of a Mesoarchean or older low δ18O source. Both scenarios require shallow crustal magmatism in emergent crust, to allow interaction with rocks altered by hydrothermal meteoric water in order to generate the low δ18O zircon. In the first scenario, assimilation of these altered rocks during Neoarchean magmatism generated low δ18O magma with which residual detrital zircons were able to exchange oxygen, while preserving their U-Pb systematics. In the second scenario, wholesale melting of the altered rocks occurred in several distinct events through the Mesoarchean, generating low δ18O magma from which zircon crystallized. Ultimately, in either scenario, the low δ18O zircons were entrained as inherited grains in a Neoarchean granite. The data suggest operation of a modern hydrological cycle by the Neoarchean and add to evidence for the increased emergence of continents by this time

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Vertically-aligned graphene flakes on nanoporous templates: morphology, thickness, and defect level control by pre-treatment

Various morphologies of the vertically-aligned graphene flakes were fabricated on the nanoporous templates treated with metal ions in solutions, as well as coated with a thin gold layer and activated in the low-temperature Ar plasma. The thickness and level of structural defects in the graphene flakes could be effectively controlled by a proper selection of the pre-treatment method. We have also demonstrated that various combinations of the flake thickness and defect levels can be obtained, and the morphology and density of the graphene pattern can be effectively controlled. The result obtained could be of interest for various applications requiring fabrication of large graphene networks with controllable properties.

Histopathological features of bone regeneration in a canine segmental ulnar defect model

Background Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopaedic surgeions and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. The present study has been designed in vivo to evaluate the effects of cellular auto-transplantation of tail vertebrae on healing of experimental critical bone defect in a dog model. Methods Six indigenous breeds of dog with 32 ± 3.6 kg average weight from both sexes (5 males and 1 female) received bilateral critical-sized ulnar segmental defects. After determining the health condition, divided to 2 groups: The Group I were kept as control I (n = 1) while in Group II (experimental group; n = 5) bioactive bone implants were inserted. The defects were implanted with either autogeneic coccygeal bone grafts in dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. Animals were euthanized at 16 weeks and analyzed by histopathology. Results Histological evaluation of this new bone at sixteen weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. And also reformation cortical compartment and reconstitution of marrow space were observed at the graft-host interface together with graft resorption and necrosis responses. Finally, our data were consistent with the osteoconducting function of the tail autograft. Conclusions Our results suggested that the tail vertebrae autograft seemed to be a new source of autogenous cortical bone in order to supporting segmental long bone defects in dogs. Furthermore, cellular autotransplantation was found to be a successful replacement for the tail vertebrae allograft bone at 3-4 cm segmental defects in the canine mid- ulna. Clinical application using graft expanders or bone autotransplantation should be used carefully and requires further investigation.

Defect production due to quenching through a multicritical point

We study the generation of defects when a quantum spin system is quenched through a multicritical point by changing a parameter of the Hamiltonian as t/tau, where tau is the characteristic timescale of quenching. We argue that when a quantum system is quenched across a multicritical point, the density of defects (n) in the final state is not necessarily given by the Kibble-Zurek scaling form n similar to 1/tau(d nu)/((z nu+1)), where d is the spatial dimension, and. and z are respectively the correlation length and dynamical exponent associated with the quantum critical point. We propose a generalized scaling form of the defect density given by n similar to 1/(tau d/(2z2)), where the exponent z(2) determines the behavior of the off-diagonal term of the 2 x 2 Landau-Zener matrix at the multicritical point. This scaling is valid not only at a multicritical point but also at an ordinary critical point.

Defect-selective photothermal imaging: a sensitive tool for damage mapping in optical coatings

A defect-selective photothermal imaging system for the diagnostics of optical coatings is demonstrated. The instrument has been optimized for pump and probe parameters, detector performance, and signal processing algorithm. The imager is capable of mapping purely optical or thermal defects efficiently in coatings of low damage threshold and low absorbance. Detailed mapping of minor inhomogeneities at low pump power has been achieved through the simultaneous action of a low-noise fiber optic photothermal beam defection sensor and a common-mode-rejection demodulation (CMRD) technique. The linearity and sensitivity of the sensor have been examined theoretically and experimentally, and the signal to noise ratio improvement factor is found to be about 110 compared to a conventional bicell photodiode. The scanner is so designed that mapping of static or shock sensitive samples is possible. In the case of a sample with absolute absorptance of 3.8 x 10(-4), a change in absorptance of about 0.005 x 10(-4) has been detected without ambiguity, ensuring a contrast parameter of 760. This is about 1085% improvement over the conventional approach containing a bicell photodiode, at the same pump power. The merits of the system have been demonstrated by mapping two intentionally created damage sites in a MgF2 coating on fused silica at different excitation powers. Amplitude and phase maps were recorded for thermally thin and thick cases, and the results are compared to demonstrate a case which, in conventional imaging, would lead to a deceptive conclusion regarding the type and location of the damage. Also, a residual damage profile created by long term irradiation with high pump power density has been depicted.

Stability of Fe3+ -VO defect pairs in polycrystalline Pb(Ti,Zr)O3

The intensity of the EPR signal with g = 5.985 arising from a ferric ion â oxygen vacancy defect pair (Fe3+ â VO) in PbTiO3, varies with the extent of PbO nonstoichiometry at constant Fe3+ content due to an increased oxygen vacancy concentration. In PZT solid solutions, the signal intensity decreases with an increase in Zr. A lower intensity is also noticed for Fe3+ â VO signals in PbZrO3. This behaviour is explained on the basis of PbO nonstoichiometry arising from independent Pb- and O-vacancies as well as the randomly distributed crystallographic shear (CS) plane defects. The contribution to PbO nonstoichiometry from CS planes is larger in high zirconium compositions of PZT.

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4-5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.