論文名稱:

以局部基因治療方法合併給予骨形成蛋白四號及血管內皮生長因子對顱顏骨缺損的影響

 

The effect of combined BMP-4 and VEGF local gene therapy in craniofacial osseous defects

研究生:

陳建鈞  Jian-Jyun Chen

 

(以作者名查詢陽明大學館藏系統)

 

(以作者名查詢全國圖書書目資訊網)

指導教授:

陳恆理  Hen-Li Chen

        學位類別:

碩士

        學校名稱:

國立陽明大學

系所名稱:

口腔生物研究所

            學號:

39217006

          學年度:

93

          語文別:

中文

          出版年:

94

關鍵字:

活化基因基質  GAMs

全文說明:

(本論文 20070824 對校內公開)

 

電子全文

        論文頁數:

89

摘要:

顱顏骨缺損是牙科臨床上常見的情形,傳統骨移植治療往往仍無法達到理想結果。研究指出骨形成蛋白 (BMPs) 及血管內皮生長因子 (VEGF) 均可促進骨生成,且可有協同作用。活化基因基質 (GAM) 技術是一種非病毒性的基因療法,雖基因轉移之效率一般不如病毒性基因療法,但曾被用來局部產生骨生成因子而促進長骨缺損骨再生,其安全性高,應適於治療顱顏骨缺損等不具生命危險性的狀況,惟至今在膜內骨之相關研究仍甚少。本計畫目的在探討藉GAM技術合併給予BMP-4VEGF165 在顱顏骨缺損的作用。在40隻大鼠顱頂骨製做直徑8毫米之骨缺損,每組10隻利用GAM技術分別未給予因子(控制組)或給予BMP-4VEGF165BMP-4/VEGF1658週後觀察其結果。實驗結果顯示相較於控制組,實驗組均有較多新生血管,且在BMP-4/VEGF165組最多,似有協同作用,但促進骨再生作用卻均未有明顯增加。已知BMP-4VEGF165均有促進血管新生的作用,故本研究顯示以GAM技術給予之因子在顱顏骨的缺損內確有活性,為使用GAM技術於牙科骨再生治療提供一有利支持。

   
 

Craniofacial osseous defects are common findings in dentistry. Current bone grafting treatments often lead to suboptimal healing. Previous studies indicated that both bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) can promote bone healing and can act synergistically. Gene-activated matrix (GAM) technology is a non-viral gene therapy strategy. Though with less impressive gene transfer efficiency than viral gene therapy, it has been used to deliver osteogenic factors locally and promote bone regeneration in long bones. The minimal safety concerns of GAM support its use in non-life-threatening conditions such as craniofacial osseous defects. However, the uses of GAM technology in intramembranous bone are largely unexplored. The purpose of this study was to determine the effects of combined delivery of BMP-4 and VEGF165 via GAM technology in craniofacial osseous defects. Eight-millimeter-diameter calvarial osseous defects were created in 40 rats. Ten rats per group were given control GAM (without encoding factor), BMP4-GAM, VEGF165-GAM and the BMP4/VEGF165-GAM respectively. The effects of GAMs were determined 8 weeks after treatment. Results indicated that all experimental groups, demonstrated much apparent new blood vessel formation than the control group. The angiogenic effect is greatest in of BMP4/VEGF165 group which suggested a synergistic effect of BMP4 and VEGF165. In promoting bone regeneration, the effects of GAM-delivered BMP4 and VEGF165 are not statistically significant. It is known that BMP4 and VEGF165 are capable of enhancing neovascularization. Thus, our results indicated that the GAM-delivered factors are active in intramembranous osseous defect site which provided a favorable support for the future use of GAM technology in bone regeneration therapy in dentistry.