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去礦物質骨基質與成骨蛋白之骨誘導及其臨床應用

A Review of Demineralized Bone Matrix and Bone Morphogenetic Protein Induced Osteogenesis and Their Clinical Application

摘要


早在古希臘時期,醫學之父希波格拉底(Hippocrates)便已知道骨組織具有強力的再生與修復能力。骨移植已有三百多年的歷史(1682年至今),而Senn(1889年)則是率先將鹽酸脫鈣之骨組織應用於臨床的學者。研究顯示去礦物質骨(或骨基質)種植在骨骼外部位,可誘導新骨形成;Unist等,進一步證實骨中有一非膠原性(noncollagenous)蛋白質,即成骨蛋白(bone morphogenetic protein, BMP),具有誘導新骨形成的能力。成骨蛋白應用於臨床的瓶頸,在於萃取工作難以進行,而且骨中所含的量不多。目前萃取上的困難已泰半解決,並可從牛、老鼠、兔子、人等不同動物及骨肉瘤組織中取得成骨蛋白。至於量不足的問題,則可應用遺傳工程技術,進行大量的養殖,製造出高純度的成骨蛋白;此外,可利用癌細胞不斷複製的特性,由人類骨肉瘤(osteo sarcoma)組織建立一株能夠產生成骨蛋白的細胞株(cell line)。當然,去礦物質骨基質或成骨蛋白應用於臨床時,疾病傳染的防制是最基本也是最重要的課題之一。亦即從骨組織的收集、處理、製造到應用於患者身上,必須謹慎篩選、小心應用,才能將疾病傳染的機會降到最低。本文主要介紹去礦物質骨與成骨蛋白所誘導之骨生成及其臨床應用之展望。

並列摘要


The remarkable potential for regeneration and repair in bone has been known from the days of Hippocrates in ancient Greece. A report in 1682 described the use f bone graft to repair osseous defects. And the use of HCl-demineralized implant for osseous reconstruction was reported in 1889 by Senn. Implantation of demineralized bone matrix (DMBM) in extraskeletal sites stimulates new bone formation. Urist and coworkers presented substantial evidence that there is a noncollagenous protein (i.e. bone morphogenetic protein, BMP) that has an ability to induced bone formation. Bone morphogenetic protein has derived from rabbit dentin; from rat, rabbit, bovine and human bone matrix; and from mouse and human osteosarcoma tissues. The potential applications for bone morphogenetic protein are numerous. At present, the main limiting factors are the small amount of purified BMP, and the large expense associated with isolation and purification. To obtain large amount of BMP, the practical approaches include: (1) using of recombinant DNA technology to isolate and express human protein from a highly purified preparation BMP. (2) establishment of a cell line producing bone morphogenetic protein from human osteosarcoma tissue. Finally, prevention of infectious diseases is one of the most important issues associated with application of demineralized bone matrix and morphogenetic protein. This paper is a review of DMBM and BMP induced osteogenesis and their clinical application.

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