骨成形蛋白併用生物相容載體在牙周骨組織工程應用之現況

Combination of Bone Morphogenetic Proteins with Biocompatible Scaffolds in Periodontal Tissue Engineering: Current Status

組織工程學的領域橫跨工程及生命科技兩個學門，藉由隔離培養細胞或製造相容替代品、加入誘導生長因子、植入生物相容支架載體等方法，以達到組織器官的修補、置換、或是再生。應用在牙周病治療的領域則是以骨組織再生為主，由於傳統治療術式並不能提供可預期的再生結果，自1961年起，即有許多學者進行牙周再生移植物質的研究；而在生物相容支架載體的研究，則是由1982年濾膜的使用建構出導引組織再生手術的觀念開始，再生骨組織替代物（同種及異種骨、硬腦膜、骨膜、氫氧磷灰石製品等）之應用，經過多年的改良，目前的兩大主流載體是以膠原蛋白為主的天然產物、和以多乳酸類聚合物或以多乳酸和甘醇酸共同聚合物為主的合成產物。而隨著生物科技的進展，具誘導生長之活性分子物質，如富含血小板血漿、牙釉基質蛋白、以及多種骨成形蛋白等成為目前臨床研究上最具發展潛力之誘導再生物質。這些具有誘導再生之活性物質必須藉由有良好生物相容性的載體方可發揮持續性釋放而延長其作用時間和功效。依目前最新文獻之報導，常用的膠原蛋白載體則有其吸收快、機械強度性質不足的缺點；而多乳酸類聚合物或多乳酸與甘醇酸之共同聚合物則其仍有疏水性、蛋白質結合力量不佳、聚合物載體內加入活性因子分佈不均等缺點。因此現今在牙周骨組織再生醫學領域中，如何改良載體性質並使加入的活性因子或蛋白能均勻分佈而且緊密結合，並且兼顧其生物相容性和逐漸分解性以達到加入之因子可持續釋放足夠之局部濃度，實為未來最重要的研究課題。

Abstract: in order to repair, regenerate, and replace damaged tissue or organ induced either by diseases or trauma, various fields of emerging biotechnology and biomaterials are converging into the discipline of tissue engineering. Currently, the term ‘‘tissue engineering’’ has come to integrate tissue substitutes or isolated cells, scaffold materials, and bioactive peptides or molecules and is, at the beginning, used to guide repair, replacement or new formation of a wide variety of tissues. Osteogenesis is a pivotal issue in the field of periodontal regeneration. Traditional periodontal treatment is unable to fulfill our goals in tissue regeneration. Clinical research in bone substitute graft for treatment of periodontal osseous defects had been started in early 1960. However, clinical results are not predictable. In 1982, Nyman proposed a “cell exclusion technique by membrane barrier” and successfully used Millipore as a barrier membrane to protect the bone defects, and finally gained bone regeneration of the defects (the concept of “Guided Tissue Regeneration”). Thereafter, various bone substitutes, and implanted scaffolds with or without active peptide or factors, irrespective of natural materials or biosynthetic, are subjected to intensive investigation. Today, the most prevalent implanted materials for guided tissue regeneration and regenerative medicine are collagen-related and high molecular weight biosynthetic materials including polylactic acid polymers, or copolymer of polylactic acid and polyglycolic acid. Due to a rapid progress of knowledge and technique in the field of biotechnology, the bioactive peptides or factors, such as platelet-rich plasma (PRP), enamel matrix-derived protein, and many bone morphogenetic proteins, have been actively integrated into clinical application and become the most important potential scaffold candidates in regenerative medicine. To effectively utilize the biological activity of these bioactive peptides, combination of them with biocompatible scaffold is mandatory. However, there are still many shortcomings in their chemical and biological properties such as rates of resorption, sustained release of incorporated peptides, mechanical strength etc., no matter of natural or synthetic scaffold. The future work in the field of periodontal tissue engineering must be focused on the improvement of physical, chemical, and mechanical properties of these scaffolds when they are used in combination with bioactive peptides.