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Available from: Shinji Kuroda, Sep 09, 2014
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    ABSTRACT: Controversy exists over the potency of bone healing in the aged skeleton, and there is concern that enhancement of bone regeneration after use of bone-stimulating growth factors may not be effective in the aged. In this study, 30 skeletally mature beagles (1-2 or 10-12 years old) had titanium implants placed bilaterally in the proximal humerus for a period of 4 weeks in a model of intramembranous bone regeneration. A bony defect made at the time of surgery created a 3-mm gap between the implant surface and the host bone. Some of the implants were treated with recombinant human TGFbeta2 (rhTGFbeta2) at various does (0.32-35 microg per implant), and some served as paired controls. The dose response was similar in young and old animals. The most effective dose, 35 microg, led to a 3-fold increase in the volume fraction of new bone within the gap in both the young (p = 0.001) and old (p = 0.002) animals. At this dose, there was a 5-fold increase in osteoblast surface. While age did not significantly affect the quantity of new bone formed as assessed by backscatter scanning electron microscopy, the older animals had thinner regenerated trabeculae that tended to be spaced more closely than the younger animals. Coupled with the finding that the increase in osteoid was greater in the old animals compared with the young animals, these qualitative differences suggest that there may have been a slight delay in the rate or a defect of mineralization in the old animals.
    Journal of Bone and Mineral Research 05/2003; 18(4):730-6. DOI:10.1359/jbmr.2003.18.4.730 · 6.83 Impact Factor
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    ABSTRACT: The purpose of the present study was to determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated implants and gap healing around the implants. In the presence of a 3-mm gap between the implant and host bone, porous-coated implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs. In three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in buffer at a dose of 100 microg/implant (n=5), 400 microg/implant (n=6), or 800 microg/implant (n=5) and placed in the left humerus. In these same animals, an internal control implant was treated only with HA/TCP and buffer and placed in the right humerus. These groups were compared with a previously reported external control group of seven animals in which no growth factor was delivered [J. Orthop. Res. 19 (2001) 85]. The BMP treated implants in the two lower dose groups had significantly more bone ingrowth than the external controls with the greatest effect in the 100 g/implant group (a 3.5-fold increase over the external control, p=0.008). All three dose groups had significantly more bone formation in the 3-mm gap surrounding the BMP treated implants than the external controls with the greatest effect in the 800 microg group (2.9-fold increase, p<0.001). Thus, application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth and gap healing. The enhancement of bone formation within the implant (bone ingrowth) was inversely related to dose.
    Journal of Orthopaedic Research 01/2004; 22(1):58-65. DOI:10.1016/S0736-0266(03)00127-X · 2.99 Impact Factor
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    ABSTRACT: The repair of hemopoietic bone marrow following evacuation of the tibial or femoral cavity of the rat was sequentially studied with the light microscope. A stereotyped train of histologic events occurred. These were capillary invasion of the cavity, appearance of primitive mesenchymal cells, osteoblastic proliferation, cancellous bone formation, development of sinusoids, reappearance of hemopoietic tissue and resorption of cancellous bone. The studies suggest that restoration of marrow sinusoids takes place only in the interstices of cancellous bone. Mechanical disruption of the sinusoidal system is one method of triggering cancellous bone formation. The cancellous bone which appeared after injury was thought to be produced by endosteal osteoblasts and osteoblasts derived from cells residing in normal hemopoietic tissue. Localized radiation of the tibia followed by mechanical disruption of hemopoietic tissue demonstrated that cancellous bone production and the repair process were unimpaired by 1,000 r but were completely blocked by 4,000 r. This would imply that the cell which can differentiate into an osteoblast is resistant to 1,000 r.
    The Anatomical Record 05/1969; 164(1):101-11. DOI:10.1002/ar.1091640107
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