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ACS Nano (1)
Medical engineering & physics (1)
McGill, Lawrence D. (3)
Bachus, Kent N. (1)
Chase, Kevin (1)
Ghandehari, Hamidreza (1)
Greish, Khaled (1)
Isackson, Dorthyann (1)
Lark, Karl G. (1)
Lawler, Dennis F. (1)
Miller, Shawn (1)
Nielsen, Mark (1)
Ray, Abhijit (1)
Yu, Tian (1)
Year of Publication
Influence of Geometry, Porosity and Surface Characteristics of Silica Nanoparticles on Acute Toxicity: Their Vasculature Effect and Tolerance Threshold
Silica nanoparticles (SiO2) are widely used in biomedical applications such as drug delivery, cell tracking and gene transfection. The capability to control the geometry, porosity, and surface characteristics of SiO2 further provides new opportunities for their applications in nanomedicine. Concerns however remain about the potential toxic effects of SiO2 upon exposure to biological systems. In the present study, the acute toxicity of SiO2 of systematically varied geometry, porosity and surface characteristics was evaluated in immune-competent mice when administered intravenously. Results suggest that in vivo toxicity of SiO2 was mainly influenced by nanoparticle porosity and surface characteristics. The maximum tolerated dose (MTD) increased in the following order: Mesoporous SiO2 (aspect ratio 1, 2, 8) at 30 – 65 mg/kg < amine-modified mesoporous SiO2 (aspect ratio 1, 2, 8) at 100 – 150 mg/kg < unmodified or amine-modified nonporous SiO2 at 450 mg/kg. The adverse reactions above MTDs were primarily caused by the mechanical obstruction of SiO2 in the vasculature that led to congestion in multiple vital organs and subsequent organ failure. It was revealed that hydrodynamic sizes of SiO2 post protein exposure had an important implication in relating SiO2 physicochemical properties with their vasculature impact and resultant tolerance threshold, as the larger the hydrodynamic size in the presence of serum protein, the lower the MTD. This study sheds light on the rational design of SiO2 to minimize in vivo toxicity and provides a critical guideline in selecting SiO2 as the appropriate system for nanomedicine applications.
Silica nanoparticles; mesoporous; geometry; acute toxicity
Age relationships of postmortem observations in Portuguese Water Dogs
Lawler, Dennis F.
Lark, Karl G.
A dog model has been used to evaluate histological changes arising from senescence. Autopsies of 145 Portuguese Water Dogs have been used to evaluate the individual and group “state of health” at time of death. For each dog, weights or dimensions of organs or tissues were obtained, together with histological evaluation of tissues. Twenty-three morphological metrics correlated significantly to age at death. Many of these involved muscles; others were associated with derivatives of embryonic foregut. The latter included lengths of the small intestine and trachea as well as weights of the stomach and some lung lobes. Nearly all of the dogs examined had histological changes in multiple tissues, ranging from two to 12 per dog. Associations among pathologies included inflammatory bowel disease with osteoporosis and dental calculus/periodontitis with atherosclerosis and amyloidosis. In addition, two clusters of histological changes were correlated to aging: hyperplasia, frequency of adenomas, and hemosiderosis constituted one group; inflammation, plasmacytic and lymphocytic infiltration, fibrosis, and atrophy, another. Heritability analysis indicated that many of the changes in tissue/organ morphology or histology could be heritable and possibly associated with IGF1, but more autopsies will be required to substantiate these genetic relationships.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-010-9181-5) contains supplementary material, which is available to authorized users.
Age of death; Autopsy; Dog; Pathology; Histology
Percutaneous Implants with Porous Titanium Dermal Barriers: An In Vivo Evaluation of Infection Risk
Bachus, Kent N.
Medical engineering & physics
Osseointegrated percutaneous implants are a promising prosthetic alternative for a subset of amputees. However, as with all percutaneous implants, they have an increased risk of infection since they breach the skin barrier. Theoretically, host tissues could attach to the metal implant creating a barrier to infection. When compared with smooth surfaces, it is hypothesized that porous surfaces improve the attachment of the host tissues to the implant, and decrease the infection risk. In this study, 4 titanium implants, manufactured with a percutaneous post and a subcutaneous disk, were placed subcutaneously on the dorsum of eight New Zealand White rabbits. Beginning at four weeks post-op, the implants were inoculated weekly with 108 CFU Staphylococcus aureus until signs of clinical infection presented. While we were unable to detect a difference in the incidence of infection of the porous metal implants, smooth surface (no porous coating) percutaneous and subcutaneous components had a 7-fold increased risk of infection compared to the implants with a porous coating on one or both components. The porous coated implants displayed excellent tissue ingrowth into the porous structures; whereas, the smooth implants were surrounded with a thick, organized fibrotic capsule that was separated from the implant surface. This study suggests that porous coated metal percutaneous implants are at a significantly lower risk of infection when compared to smooth metal implants. The smooth surface percutaneous implants were inadequate in allowing a long-term seal to develop with the soft tissue, thus increasing vulnerability to the migration of infecting microorganisms.
Surface texture; Titanium; In vivo; Bacteria; Percutaneous
Results 1-3 (3)
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