Publications (7)9.49 Total impact
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Article: Effects of SU5416 and a vascular endothelial growth factor neutralizing antibody on wear debris-induced inflammatory osteolysis in a mouse model.
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ABSTRACT: The development of highly vascularized and inflammatory periprosthetic tissue characterizes the progress of aseptic loosening, a major complication of joint arthroplasty. Vascular endothelial growth factor (VEGF) is an important cell signaling protein involved in angiogenesis. The purpose of this study was to investigate whether R2/Fc (a VEGF neutralizing antibody) and SU5416 (a VEGF receptor II [Flk-1] inhibitor) could ameliorate particle-induced inflammatory osteolysis in a mouse model. Ultrahigh molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches in BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Drug treatment was started 2 weeks after bone implantation, and mice without drug treatment were included as controls. Pouch tissues were harvested 4 weeks after bone implantation for molecular and histological analysis, and implanted bone degradation was analyzed by microcomputed tomography. Exposure to UHMWPE particles induced inflammatory osteolysis, which was associated with increased expression of VEGF/Flt-1 proteins. Treatment with R2/Fc significantly improved UHMWPE particle-induced inflammatory osteolysis, and reduced the expression of VEGF/Flt-1 proteins. However, SU5416 treatment showed no effect on UHMWPE particle-induced inflammatory osteolysis. Our findings indicate that VEGF signaling exerts a regulatory effect on the development of UHMWPE-induced inflammatory osteolysis, through its unique Flt-1, rather than Flk-1, receptor located on monocyte/macrophage cell lineages. These data provide a biological rationale for a VEGF/Flt-1-targeted treatment strategy, especially during the early stages of the wear debris-induced inflammatory response.Journal of Inflammation Research 01/2011; 4:29-38. -
Article: Efficacy of periprosthetic erythromycin delivery for wear debris-induced inflammation and osteolysis.
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ABSTRACT: We have reported that oral erythromycin (EM) inhibits periprosthetic tissue inflammation in a group of patients with aseptic loosening. The purpose of this study was to assess the efficacy of local, periprosthetic EM delivery in a rat model. Uncoated Ti pins were press-fit into the right tibia of fourteen Sprague-Dawley rats following an intramedullar injection of UHMWPE (ultra high molecular weight polyethylene) particles. Revision surgeries were performed 2 months after the primary surgery. EM was applied to the Peri-Apatite™ (PA) layer of the titanium (Ti) pins. The previously implanted Ti pins were withdrawn and replaced with Ti pins coated either with (n = 7) or without (n = 7) EM. The rats were killed 1 month after "revision surgery". The EM efficacy was evaluated by (MicroCT) μCT and histology. μCT analysis showed that bone volume percentage (BV/TV) was significantly higher in the EM-treated group compared to the untreated group (p < 0.05). Histological analysis showed that EM treatment inhibits UHMWPE particle-induced periprosthetic tissue inflammation compared to the untreated group. This study demonstrated that periprosthetic EM delivery reduced periprosthetic inflammation and improved the quality of surrounding bone.Agents and Actions 12/2010; 59(12):1091-7. · 1.59 Impact Factor -
Article: Effects of hydroxyapatite on titanium foam as a bone ingrowth surface in acetabular shells: a canine study.
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ABSTRACT: This study investigated a highly porous titanium foam with and without a PeriApetite coating as an alternative surface for implant fixation. Twelve mongrel canines received staged total hip replacements under International Animal Care and Use Committee (IACUC) approval from our institution. Animals were randomly placed in three- or six-month groups for sacrifice. Seventeen total hips were available for evaluation. The area and depth of ingrowth was measured by SEM. At three months, PeriApetite Ti foam had 37% more depth and almost 10% more bone ingrowth. Both groups were found not to be different at the six-month mark with over 36% of ingrowth calculated on SEM. The results prove not only that titanium foam is a viable ingrowth surface but also that PA coating can enhance the time to bony incorporation.Journal of Long-Term Effects of Medical Implants 01/2010; 20(1):35-42. -
Article: An in vivo evaluation of bone response to three implant surfaces using a rabbit intramedullary rod model.
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ABSTRACT: Our study was designed to evaluate osseointegration among implants with three surface treatments: plasma-sprayed titanium (P), plasma-sprayed titanium with hydroxyapatite (PHA), and chemical-textured titanium with hydroxyapatite (CHA). Average surface roughness (Ra) was 27 microns for the P group, 17 microns for the PHA group, and 26 microns for the CHA group. Bilateral distal intramedullary implants were placed in the femora of thirty rabbits. Histomorphometry of scanning electron microscopy images was used to analyze the amount of bone around the implants at 6 and 12 weeks after implantation. Greater amounts of osseointegration were observed in the hydroxyapatite-coated groups than in the noncoated group. For all implant surfaces, osseointegration was greater at the diaphyseal level compared to the metaphyseal level. No significant differences were seen in osseointegration between the 6 and 12 week time points. Although the average surface roughness of the P and the CHA groups was similar, osseointegration of the CHA implants was significantly greater. The results of this in vivo lapine study suggest that the presence of an hydroxyapatite coating enhances osseointegration despite similarities in average surface roughness.Journal of Orthopaedic Surgery and Research 01/2010; 5:57. -
Article: Inhibitory effects of erythromycin on wear debris-induced VEGF/Flt-1 gene production and osteolysis.
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ABSTRACT: A highly vascularized and inflammatory periprosthetic tissue augments the progress of aseptic loosening, a major clinical problem after total joint replacement. The purpose of this study is to investigate the effect of erythromycin (EM) on ultra high molecular weight polyethylene (UHMWPE) particle-induced VEGF/VEGF receptor 1 (Flt-1) gene production and inflammatory osteolysis in a mouse model. UHMWPE particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. EM treatment started 2 weeks after bone implantation (5 mg/kg day, i.p. injection). Mice without drug treatment as well as mice injected with saline alone were included. Pouch tissues were harvested 2 weeks after bone implantation. Expression of VEGF, Flt-1, RANKL, IL-1, TNF and CD68 was measured by immunostain and RT-PCR, and implanted bone resorption was analyzed by micro-CT (muCT). Exposure to UHMWPE induced pouch tissue inflammation, increase of VEGF/Flt-1 proteins, and increased bone resorption. EM treatment significantly improved UHMWPE particle-induced tissue inflammation, reduced VEGF/Flt-1 protein expression, and diminished the number of TRAP(+) cells, as well as the implanted bone resorption. This study demonstrated that EM inhibited VEGF and Flt-1 gene expression. The molecular mechanism of EM action on VEGF/Flt-1 signaling-mediated osteoclastogenesis warrants further investigation.Agents and Actions 04/2009; 58(7):413-21. · 1.59 Impact Factor -
Article: Blockade of vascular endothelial growth factor activity suppresses wear debris-induced inflammatory osteolysis.
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ABSTRACT: Aseptic loosening is a common complication of total joint replacement in humans. Our study examined the hypothesis that wear debris may influence vascular endothelial grow factor (VEGF) expression, and that blocking VEGF bioactivity might improve wear debris-induced inflammatory osteolysis in a mouse model. Ultra high molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Mice were treated with recombinant VEGF, or VEGF inhibitor (VEGF R2/Fc chimera) or vehicle control, and mice without UHMWPE stimulation were also included. Pouch tissues were harvested 2 weeks after bone implantation for molecular and histological analyses. Exposure of UHMWPE particles increased VEGF expression at both mRNA and protein levels in pouch tissues. Immunostaining revealed intense VEGF staining predominantly in UHMWPE deposit foci surrounded by inflammatory cells. VEGF inhibitor treatment strongly attenuated tissue inflammation (cellular infiltration, membrane proliferation, and expression of interleukin 1beta and tumor necrosis factor-alpha in UHMWPE-stimulated pouch tissues). Further, VEGF inhibitor treatment caused a significant reduction in the number of TRAP+ cells, and effectively prevented UHMWPE particle-induced bone resorption of implanted calvaria (assessed by extent of collagen depletion and frequency of bone erosions). The observation that VEGF inhibitor treatment prevented UHMWPE particle-induced inflammatory osteolysis opens new possibilities for treatment of aseptic loosening, especially at an early stage.The Journal of Rheumatology 02/2007; 34(1):27-35. · 3.69 Impact Factor -
Article: Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatite.
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ABSTRACT: Solution precipitation of calcium and phosphate is a technique to generate hydroxyapatite [Peri-Apatitetrade mark (PA), Stryker Orthopaedics, Mahwah, NJ] on metal substrate. This study was carried out to determine the capacity of PA to adsorb osteogenic protein-1 (OP-1) and the time course of release, and to determine the osteoinductive activity of OP-1. The adsorption and release studies were conducted with (125)I-labeled OP-1- and PA-coated titanium alloy disks. The results indicate that the adsorption of OP-1 on the PA-coated disks is linear with the concentration of OP-1 up to 5 mg/mL. There is an initial release of 75% to 80% of adsorbed OP-1 within the first hour, and 92% of OP-1 is released in 3 days. The osteoinductive activity of OP-1 was determined in the rat intramuscular ectopic bone formation assay. A total of 24 titanium alloy disks were evenly divided into 3 groups with different treatments for implantation, plain disks (group A), disks coated with PA (group B), and disks coated with PA plus 40 microg OP-1 (group C). Osteogenic protein-1, 40 microg in solution, was injected into the muscle pouch in animals of group D (n = 8). The rats were sacrificed 3 weeks postoperatively and the implants were retrieved. Ectopic bone formation was evaluated with radiography and histology. Results demonstrated that OP-1 induced ectopic bone in all the animals of group C and group D. The titanium alloy disks were surrounded by trabecular bone and marrow tissue. None of the animals of group A or group B showed any evidence of osteoinduction. Our findings indicate that PA can deliver OP-1 directly to titanium alloy implants and maintain the osteoinductive activity of OP-1.Journal of Biomedical Materials Research Part A 01/2005; 71(3):412-8. · 2.63 Impact Factor
Top co-authors
Top Journals
Institutions
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2010
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University of Tennessee
Knoxville, TN, USA
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2005
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Stryker Corporation
Kalamazoo, MI, USA
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