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1.  Mesenchymal Stem Cells Increase Collagen Infiltration and Improve Wound Healing Response to Porous Titanium Percutaneous Implants 
Medical engineering & physics  2012;35(6):743-753.
Epidermal downgrowth, commonly associated with long-term percutaneous implants, weakens the skin-implant seal and greatly increases the vulnerability of the site to infection. To improve the skin attachment and early tissue integration with porous metal percutaneous implants, we evaluated the effect of bone marrow-derived mesenchymal stem cells (BMMSCs) to provide wound healing cues and vascularization to the dermal and epidermal tissues in establishing a barrier with the implant. Two porous metal percutaneous implants, one treated with BMMSCs and one untreated, were placed subdermally on the dorsum of Lewis rats. Implants were evaluated at 0, 3, 7, 28, and 56 days after implantation. Histological analyses evaluated cellular infiltrates, vascularization, quantity and quality of tissue ingrowth, epidermal downgrowth, and fibrous encapsulation. The amount of collagen infiltrating the porous coating was significantly greater for the BMMSC-treated implants at 3 and 28 days post implantation compared to untreated implants. There was an early influx and resolution of cellular inflammatory infiltrates in the treated implants compared to the untreated, though not statistically significant. Vascularization increased over time in both treated and untreated implants, with no statistical significance. Epidermal downgrowth was minimally observed in all implants with or without the BMMSC treatment. Our results suggest that BMMSCs can influence an early and rapid resolution of acute and chronic inflammation in wound healing, and can stimulate early collagen deposition and granulation tissue associated with later stages of wound repair. These findings provide evidence that BMMSCs can stimulate a more rapid and improved barrier between the skin and porous metal percutaneous implant.
PMCID: PMC3529992  PMID: 22940446
Porous titanium; in vivo; mesenchymal stem cells; percutaneous implant
2.  Influence of Geometry, Porosity and Surface Characteristics of Silica Nanoparticles on Acute Toxicity: Their Vasculature Effect and Tolerance Threshold 
ACS Nano  2012;6(3):2289-2301.
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.
PMCID: PMC3357903  PMID: 22364198
Silica nanoparticles; mesoporous; geometry; acute toxicity
3.  Age relationships of postmortem observations in Portuguese Water Dogs 
Age  2010;33(3):461-473.
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.
PMCID: PMC3168605  PMID: 20845083
Age of death; Autopsy; Dog; Pathology; Histology
4.  Percutaneous Implants with Porous Titanium Dermal Barriers: An In Vivo Evaluation of Infection Risk 
Medical engineering & physics  2010;33(4):418-426.
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.
PMCID: PMC3071885  PMID: 21145778
Surface texture; Titanium; In vivo; Bacteria; Percutaneous

Results 1-4 (4)