2012-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644708摘要：先天或是後天之骨骼缺損一直是骨科醫學治療上之一大難題。由於人體骨骼再生能力有限並侷限於較小之骨骼缺損，因此外傷、骨髓炎或是人工植入物鬆脫後造成之大範圍骨缺損，常常需要外科進行介入性手術治療。PLGA-PEG-PLGA copolymer 為一種生物可降解之溫度敏感性水膠(Thermal-sensitive Hydrogel)；而第二型骨形成蛋白(BMP-2， Bone MorphologenicProtein-2)為骨骼再生過程中占重要角色；且已經被證明具有促進骨骼生長之作用。於本研究計畫中， 我們將使用疏水性聚酯類化合物(Hydrophobic PolyesterCompound)BOX 嵌入PLGA-PEG-PLGA 長鏈中，藉以提高其分子間疏水性，形成含有BOX 結構之水膠 (BOX Hydrogel)；並將BOX 水膠與第二型骨形成蛋白混合使用於大範圍骨隔缺損隻動物模式中；嘗試去證明利用BOX 分子與第二型骨形成蛋白之間的疏水親和力，能夠局部有效地控制骨形成蛋白質釋放，促進更優良之骨再生作用。我們將於大鼠動物模式中，於其橈骨幹中段創造一個 5-mm 長之骨骼缺損；並將24 隻實驗大鼠分為三組：僅於局部加第二型骨形成蛋白(local application of 8 μg BMP-2in type I collagen sponge)、於局部加含第二型骨形成蛋白之水膠(Col-I/BOX hydrogelsponge) 、控制組只加膠原蛋白(sham operated group with type I collagen sponge only).之後，我們將以放射線檢查(Radiographic evaluation)、組織切片(histological stains) 以及螢光染色(epifluorescence microscopy)加以評估各組骨骼再生之速度。經由本計畫之研究，我們將可以釐清膠原蛋白/ BOX 水膠是否可以有效地將骨形成蛋白控制於局部釋放並促進骨骼之再生。<br> Abstract: Congenital or acquired bone defects are major problems in orthopedic surgery. Largebone defects resulting from trauma, tumors, osteomyelitis or implant loosening usuallyrequire surgical treatment because spontaneous regeneration is limited to relatively smalldefects. PLGA-PEG-PLGA copolymer is a kind of thermal-sensitive hydrogel, and it’s alsoa well-known biodegradable material. BMP-2 plays an important role in bone formation andhas an anabolic effect on the skeleton and reportedly enhances bone ingrowth. In this study,we conjugated a hydrophobic polyester compound, BOX, into PLGA-PEG-PLGAcopolymer (BOX hydrogel). We also use an in vivo critical bone defect model to test thehypothesis that the application of BOX-hydrogel collagen can locally control the release ofBMP-2 and promotes better bone healing.A 5-mm segmental bone defect was created in the radial shaft in a rat model.Twenty-four rats were assigned to three groups: local application of 8 μg BMP-2 in type Icollagen sponge, Col-I/BOX hydrogel sponge, or sham operated group with type I collagensponge only. Radiographic evaluation, histological stains, and epifluorescence microscopywere performed.Through this project, we can validate the efficiency of collagen sponges and BOXhydrogel cooperating with BMP-2 on the critical-sized defect healing.