New type of prosthesis combined with rhBMP-2 delivery system

结合rhBMP-2输送系统的新型假体

• 批准号: 12671403
• 负责人: SAITO Naoto
• 金额: $ 2.11万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671403/
• 关键词: Bone morphogenetic protein; Carrier; Drug delivery system; Biodegradable polymer; Hip prosthesis; Bone; サイトカイン

Total hip arthroplasty is widely accepted for reconstruction of damaged hip joints in spite of potential risk for mechanical loosening and inevitable revision surgery. In such revision surgeries, we often encounter peri-prosthetic bone defects of various grades either in proximal femur or in acetabulum, which often make difficult to obtain stable setting of a new hip prosthesis even if with use of auto- or allogenous bone grafting and various biomaterials. In order to address this problem, we devised new method to repair the bone defect with use of a growth factor bone morphogenetic protein-2 of human type, produced by DNA recombination ( rhBMP-2) in combination with a new synthetic biodegradable Polymer( PLA-DX-PEG ) as a carrier material for the rhBMP-2 delivery. In this report we present the efficacy of the rhBMP-2 retaining prosthesis to reconstruct bone defect in a canine model. In this model, femoral head and medial halfofthe proximal femur was surgically resected to make the bon … More e defect to be repaired. And the prosthesis with partially porous structured Surface which was impregnated with rhBMP-2 ( 100 μ, 500 μ g or 1000 μ g )/PLA-DX-PEG( 100mg ) composite. In control animals, PLA-DX-PEG polymer without rhBMP-2 was packed into the porous surface. New bone formation at the proximal bone defects was examined by routine radiography at 2, 4, 8 and 12 weeks after surgery. In 100, 500μ g and 1,000 μ g rhBMP-2 groups ( n=4 respectively ) definite radiopaque shadows appeared along the bone defects in 4 week and the sizes of the radiopaque area were depended on the rhBMP-2 doses. The radiopaque shadows became more obvious at 8 weeks alter surgery. In control animals, no radiopaque shadow was noted at the bone defect over the experimental period of time. At 12 weeks after surgery, the animals were sacrificed and proximal femurs were harvested. On macroscopic histology and radiology, original bone defects in 500 and 1,000m μ g rhBMP-2 groups were completely repaired and thef prostheses were well fixed within the proximal femurs. In 100 μ g group, the defects were partially repaired with thin new bone. In controls, the defects were left un-repaired and covered by fibrous tissue. On light microscopic examination, the newly formed bone was remodeled to lamellar bone in 12 weeks. In summary, this type of prosthesis combined with rhBMP-2 delivery system might provide us a new modality to restore bone defect or lost bone mass encountered in revision arthroplasty without bone grafting. Less

全髋关节置换术被广泛接受用于重建受损的髋关节，尽管存在潜在的机械松动风险和不可避免的翻修手术。在这种翻修手术中，我们经常会遇到股骨近端或髋臼中各种级别的假体周围骨缺损，这通常使得即使使用自体或同种异体骨移植和各种生物材料也难以获得新髋关节假体的稳定设置。为了解决这个问题，我们设计了一种新的方法来修复骨缺损，使用的生长因子骨形态发生蛋白-2的人型，通过DNA重组（rhBMP-2）与一种新的合成的可生物降解的聚合物（PLA-DX-PEG）作为载体材料的rhBMP-2的交付。在这份报告中，我们提出了有效的rhBMP-2保留假体重建骨缺损的犬模型。在该模型中，手术切除股骨头和股骨近端的内侧半， ...更多信息 缺陷需要修复。分别用rhBMP-2（100 μ g、500 μ g、1000 μ g）/PLA-DX-PEG（100 mg）复合材料浸渍部分多孔结构的假体。在对照动物中，将不含rhBMP-2的PLA-DX-PEG聚合物填充到多孔表面中。术后2、4、8、12周行常规X线片检查骨缺损近端新骨形成情况。100、500和1,000 μ g rhBMP-2组（n=4）4周后骨缺损处沿着出现一定的不透射线影，不透射线影的大小与rhBMP-2剂量有关。术后8周，不透射线阴影变得更加明显。在对照组动物中，在实验期间，在骨缺损处未观察到不透射线阴影。术后12周，处死动物并收获近端股骨。大体组织学和X线片显示，500和1,000 μ g rhBMP-2组骨缺损完全修复，假体与股骨近端固定良好。100 μ g组骨缺损部分被较薄的新骨修复。在对照组中，缺损未修复，并被纤维组织覆盖。光镜下观察，12周后新生骨改建为板层骨。总之，这种类型的假体结合rhBMP-2输送系统可能为我们提供一种新的模式，以恢复骨缺损或骨量丢失的翻修关节置换术中遇到的不植骨。少

项目成果

Murakami N, Saito N, et al.: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. (in press).

Murakami N、Saito N 等人：“磷酸二酯酶抑制剂 4 咯利普兰对重组人骨形态发生蛋白 2 形成新骨的影响”骨。

Kinoshita T,Kobayashi S, et al.: "Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice."Bone. 27. 811-817 (2000)

Kinoshita T、Kobayashi S 等人：“磷酸二酯酶抑制剂己酮可可碱和咯利普兰主要通过促进正常小鼠的骨形成来增加骨量。”骨。

Horiuchi H,Saito N, et al.: "Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline."Bone. (in press).

Horiuchi H、Saito N 等人：“通过磷酸二酯酶抑制剂己酮可可碱增强小鼠骨形态发生蛋白 2 诱导的新骨形成。”骨。

Kobayashi S, Saito N, et al.: "Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty"Lancet. 355. 1499-1504 (2000)

Kobayashi S、Saito N 等人：“骨质量或髋部结构不良是影响全髋关节置换术存活的危险因素”《柳叶刀》。

Horiuchi,H., Saito,N., et al: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. in press.

Horiuchi,H.、Saito,N. 等人：“磷酸二酯酶抑制剂 4 咯利普兰对重组人骨形态发生蛋白 2 形成新骨的影响”Bone。