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生長因子在臨床口腔重建之應用
牙周疾病經常會造成許多組織的缺損及型態上的變異,影響的層面不但是在美觀上難以讓患者接受,在功能上也會使得治療的效
果大打折扣。因此在1982年Dr.Nyman1成功的在人體上誘導再生些許牙周組織後,各種組織再生的術式及材料便不斷的推陳出新
2-4。一般說來,組織再生療法是採取下面兩種方式;其一是將骨移植材料( bone replacement
materials)填入缺損區5,6,期望 能引導骨細胞長入將骨移植材料( bone replacement
materials)填入缺損區5,6,期望能引導骨細胞長入移植物的縫隙,進而在 移植材料吸收後取而代之型成新的齒槽骨。這些移植材料包括了自體骨(autogenous
bone)以及一些他種生物骨骼或是人工聚合物 經過工業程序處理的顆粒狀生化材料(biomaterials)。第二種策略則是把希望將來新生組織所在位置的空間騰出7,8,加入生長因
子以引導細胞分化,並形成新的組織填補舊有的缺損。在臨床治療上也有許多同時運用上述兩種策略的治療方式及相關的研究報告
9,10。
雖然誘導牙周組織再生已有一定的成效,但是在誘導骨再生方面,尤其是顎骨的垂直誘導生長一直無法有效的突破,即使加入了許
多人工移植材料離真正的顎骨再生仍有一大段距離11-14。
生長因子(growth factor)泛指一些可以增進細胞分裂(mitogenesis)的胜太鏈化合物,其中更有一些特殊的生長因子還具有吸引未分化幹細胞趨化(chemotaxis)
,以及趨使這些幹細胞分化(differentiation)為成熟組織細胞的能力。早期生長因子的來源通常是由生物組織提煉而來,不但難以增加產量15,也存在著病源傳染的疑慮16,17。隨著生物科技的發達,再加上人類基因的解碼,一些藥廠已經能採用生化合成的技術大量製造純度高的特定生長因子18。部份生長因子已經可以應用在組織再生的治療上了,許多的文獻也記載了在某些特定的情況下,生長因子確實能加快傷口癒合的速度和增加局部組織再生的能力19-21。
目前在牙醫科學方面有較深入的研究並進入人體試驗階段的包括了BMP
(bone morphogenetic protein), PDGF (platelet-derived
growth factors), 和 EMD (enamel matrix derivative)。生長因子在人體上的臨床應用包括牙周再生
(Periodontal Regeneration)、顱顏重建(Maxillofacial Reconstruction)、牙脊保存和增高術(Ridge
Preservation and Augmentation)、與上顎竇增進術 (Sinus Augmentation)
22-30。其中EMD已經商品化(Emdogain Gel )並已廣泛的運用在牙周組織再生的治療中了 31。
雖然許多動物實驗證實了生長因子的正面成效,但是在人體試驗的效果評估中卻沒辦法得到穩定的結果,這可能是因為受試者並不是在嚴格控管的實驗室生活,以及高等哺乳類動物常有的個體差異性
(individual variety) 造成的32,33,這包括了對外來生長因子的免疫反應,及本身幹細胞的多寡或分化能力等種種因素。此外,目前並無許多長期研究的證據可以顯示這些經由生長因子引導而生成的組織是否會產生其他的變化,以及是否具有長期的穩定性等等問題。
對於生長因子在牙醫科學上的應用,學界是以樂觀其成的態度來面對,但現階段則是由謹慎評估的方向來切入,小心求證,期待生長因子能在人體的臨床應用上達到安全及效果兼備的治療目的。
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註一: 本文同步刊載於
中華民國牙周病醫學會雜誌 第九卷第四期291頁
註二: 本頁有其它連結至賓州牙周暨顱顏再生應用技術實驗室(LAPCR)
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