Biomedical subjects

Renwen Zhang

Publications and source records attributed to Renwen Zhang.

5 recordsLinked to original sources

PubMed2007

Blockade of vascular endothelial growth factor activity suppresses wear debris-induced inflammatory osteolysis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Animals↗

PubMed2006

Association between UHMWPE particle-induced inflammatory osteoclastogenesis and expression of RANKL, VEGF, and Flt-1 in vivo.

Wear debris-induced vascularized granulomatous periprosthetic tissue may augment the progress of prosthetic loosening, a major clinical problem after total joint replacement. The purpose of this study is to investigate the association of ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced inflammatory osteoclastogenesis and expression of RANK/RANKL and VEGF/VEGF receptors (Flt-1 and Flk-1) using a mouse osteolysis model. UHMWPE particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Mice were injected with either recombinant VEGF or VEGF inhibitor (VEGF R2/F(c) Chimera). Mice without drug treatment, as well as mice injected with saline alone were included. Each group contains 10 mice. Pouch tissues were harvested 2 weeks after bone implantation for histological and molecular analysis. UHMWPE stimulation significantly increased VEGF gene expression, and exerted a lower enhancement effect on the gene expression of Flt-1 and Flk-1. UHMWPE-stimulated VEGF production was markedly reduced by VEGF inhibitor treatment. Immunofluorescent staining indicated that pouch tissue macrophages were the main source of both VEGF and Flt-1 production. A positive association was observed between tissue inflammation and the levels of VEGF and Flt-1 gene transcripts. Both RANK and RANKL gene transcripts were significantly increased by UHMWPE stimulation, which was subsequently reduced by VEGF inhibitor treatment (p<0.05). VEGF treatment increased TRAP(+) cells in pouches either with or without UHMWPE particle stimulation, and VEGF inhibitor treatment caused a significant reduction in the number of TRAP(+) cells in UHMWPE-containing pouches. This study suggests that VEGF has a role in the regulation of RANK/RANKL-mediated osteoclastogenesis, and warrant future investigations to elucidate the role of VEGF signaling in the pathogenesis of prosthetic loosening.

Animals↗

PubMed2005

Tendon reattachment to a metallic implant using an allogenic bone plate augmented with rhOP-1 vs. autogenous cancellous bone and marrow in a canine model.

Functionality of endoprosthetic reconstruction may be improved through secure and lasting soft tissue reattachment directly to the metallic implant surface. Tendon reattachment to the metallic surface of a titanium implant (enhanced tendon anchor, ETA) using autogenous bone plate as an interpositional structure between the tendon and metal, augmented with autogenous bone chips and marrow, provided successful mechanical and functional outcome. However, preparation of the autogenous bone plate is not practical in a clinical setting, but application of an allogenic bone plate could be an alternative. The autogenous cancellous bone and marrow may also be substituted by bone growth factors so that no autogenous bone graft is required. We hypothesized that the reconstitution of the direct tendon-bone insertion morphology in tendon reattachment to metallic implant could be achieved using allogenic cancellous bone plate augmented with autogenous cancellous bone and marrow, and that the autogenous bone grafts could be replaced by recombinant human osteogenic protein-1 (rhOP-1). In two canine groups the supraspinatus tendon was reattached unilaterally to a modified ETA implant with a highly porous metallic surface known as Tritanium Dimensionalized Metal. Allogenic bone plates saturated with rhOP-1-collagen putty were used in the OP-1 (OP) group, while plates saturated with autogenous cancellous bone and marrow were used in the bone marrow (BM) group. Functional, radiographical, mechanical and histomorphological analysis results were compared between both groups. At 15 weeks, gait analysis showed 78% and 81% recovery of preoperative weight-bearing in OP and BM groups, respectively. The calcified area around the tendon in OP group was 5.2 times larger than that in BM group (p<0.001). The ultimate tensile strength of the reattachment was 24% and 38% of the intact contralateral side in OP and BM groups, respectively, without significant difference between them. There was evidence of tendon-bone insertion transitional zones, tissue ingrowth and adhesion to the metallic surface in both groups. In conclusion, the use of the allograft combined with rhOP-1 had a similar effect as combined with autogenous cancellous bone and marrow in the tendon reattachment to the metallic surface.

Animals↗

PubMed2004

Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatite.

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.

Absorption↗

PubMed2004

Osteogenic protein-1 enhances osseointegration of titanium implants coated with peri-apatite in rabbit femoral defect.

This study evaluated the effect of osteogenic protein-1 (OP-1) carried by Peri-Apatite (PA) on bone healing in the gap surrounding implants in a rabbit model. Cylindrical titanium implants (3 x 9 mm) were uniformly coated with PA precipitated from a calcium and phosphate solution. OP-1 solution containing 60 microg OP-1 was directly loaded on the implants immediately before implantation for the experimental group, whereas buffer solution was loaded on the implants for the control. The implant was placed in the distal femur and surrounded by a 1-mm gap. The implants were retrieved and examined 6 weeks after implantation. Mechanical testing (push-out) data showed that OP-1 enhanced implant fixation by 80%. Histomorphometric measurements indicated that bone ingrowth in the initial gap expressed as a percentage of the whole gap was significantly higher in the specimens treated with OP-1 than the control group (25.4% vs. 8.9%, p < 0.05). The percentage of the surface of implants, which was covered by bone, was significantly higher in the OP-1-treated group compared to the control group (65% vs. 25%, p < 0.05). This study suggests that OP-1 can be loaded on orthopedic implants through PA to enhance the osseointegration of orthopedic implant.

Alloys↗