New type of prosthesis combined with rhBMP-2 delivery system

结合rhBMP-2输送系统的新型假体

基本信息

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

项目摘要

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

尽管有潜在的机械松动和不可避免的修订手术风险，但总髋关节置换术被广泛接受，以重建受损的髋关节。在这样的修订手术中，我们经常在股骨近端或髋臼中遇到各种级别的肢体骨缺陷，即使使用自动或同种异性骨嫁接和各种生物材料，这通常很难获得新的髋关节假体的稳定设置。为了解决这个问题，我们设计了新的方法来通过使用生长因子骨形态蛋白2的人类类型修复骨缺损，该方法由DNA重组（RHBMP-2）与新的合成生物降解聚合物（PLA-DX-PEG）结合使用，作为RHBMP-2递送的载体材料。在本报告中，我们介绍了RHBMP-2保留假体以在犬模型中重建骨缺损的效率。在此模型中，股骨头和股骨近端的一半是通过手术切除的，以使BON…更多的E缺陷要修复。以及部分多孔结构表面的假体，该表面被RHBMP-2（100μ，500μg或1000μg）/PLA-DX-PEG（100 mg）复合浸渍。在对照动物中，将没有RHBMP-2的PLA-DX-PEG聚合物填充到多孔表面。在手术后2、4、8和12周，通过常规X线照相检查近端骨缺损处的新骨形成。在100、500μg和1,000μgRHBMP-2组（分别为n = 4）中，定义的放射性阴影在4周内沿着骨缺损出现，而放射性区域的大小取决于Rhbmp-2剂量。在8周改变手术时，Radiopaque阴影变得更加明显。在对照动物中，在实验期间，骨骼缺陷未发现辐射阴影。手术后12周，处死动物并收获近端股骨。在宏观组织学和放射学上，对500和1,000mμgRHBMP-2组的原始骨骼缺损进行了完全修复，并且F假体在近端股骨内得到了很好的固定。在100μg组中，将缺陷用薄的新骨部分修复。在对照组中，缺陷未修复并被纤维组织覆盖。在光学显微镜检查中，新形成的骨头在12周内重塑为层状骨。总而言之，这种类型的假体与RHBMP-2递送系统相结合，可能为我们提供了一种新的方式来恢复骨缺损或在不骨移植的情况下遇到的骨骼缺陷或失去的骨骼质量。较少的