- 學位論文
天然高分子複合凍膠於齒槽骨增生之應用
Application of Natural Polymeric Composite Cryogel in Alveolar Bone Regeneration
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摘要
齒槽骨由膠質、礦物質、纖維蛋白及基質所構成，與牙齒是互相共同存在的關係，因此當牙齒拔除後就會出現齒槽骨慢慢萎縮的現象並逐漸消失。為了拔牙術後傷口感染及減緩齒槽骨萎縮，在拔牙後建議立即置入牙創填補物以防止牙槽骨損失和縮短整個治療期。目前臨床上所使用牙創材大多為單一成分，而且降解速度過快，使得齒槽骨增生效果有限，因此，如何開發出更適合拔牙術後減緩齒槽骨持續流失的牙創材為本研究動機。凍膠為多孔網狀結構，在多孔結構中可充滿介質液體，當內部移除液體後，體積會逐漸縮小，若重新吸收液體後，則體積會再膨脹變大。因凍膠具有很好的膨潤性，於拔牙後立即使用凍膠，當凍膠放入齒槽骨窩洞並吸附血水膨脹後回復到原本大小時，可以預留空間讓齒槽骨生長並預防齒槽骨過度萎縮，膨脹後的凍膠也能以物理的方式對傷口進行止血的作用，也能達到預防感染、減少疼痛的效果。明膠為膠原蛋白質水解後的產物，具有良好生物相容性，可使細胞聚集增生，以促進傷口癒合，同時明膠亦具有止血功能，因此本研究將以明膠 (Gelatin)為凍膠基材。透明質酸是廣泛分佈在細胞外基質中的水溶性多醣，對於細胞的聚集、遷移、增生及分化具有重要的影響；硫酸軟骨素通過與生長因子的硫酸化依賴性結合過程促進細胞發育及生長；而絲素蛋白具有優異的機械性能。因此，本研究目的以明膠為基材混摻透明質酸、硫酸軟骨及絲素蛋白製作成複合凍膠，探 討凍膠做為齒槽骨修復的可行性。研究結果顯示，含水量是以明膠為基材(A組)以 及添加透明質酸的凍膠(B組)，這兩個組別的含水量較為顯著，膨潤率也是以A、B兩個組別較為顯著，降解速率則以添加明膠、絲素蛋白、透明質酸與硫酸軟骨素， 四種複合式凍膠(H組)有較低的降解速率。在細胞毒性測試顯示，所有的材料對細胞皆沒有毒性，在骨性細胞培養測試顯示添加了絲素蛋白與透明質酸有助於細胞的增生，以第七天最為顯著。實驗結果顯示天然高分子的添加確實改變且改善了原材料的不足與應用，其中添加了硫酸軟骨素的組別皆顯示促進骨細胞增生與分化的能力。期望本研究的結果可以帶給臨床更多的選擇。
並列摘要
The alveolar bone and the teeth are coexisting with each other. The alveolar bone is composed of colloid, minerals, fibrin and matrix. Therefore, when the tooth is extracted, it will absorb and gradually disappear. Use cryogel immediately after tooth extraction. When the cryogel is put into the cavity of the alveolar bone and absorbs blood and swells to its original size, it can reserve space for the growth of the alveolar bone and prevent excessive atrophy of the alveolar bone. The expanded cryogel can also physically treat the wound. Hemostasis can also prevent infection and reduce pain. The successful treatment of the wound requires ensuring a reduction in the amount of necrotic tissue and prevention of microbial intrusion, so immediate placement after extraction is recommended to prevent alveolar bone loss and shorten the overall treatment period. Therefore, the purpose of this study was to use gelatin as the base material to mix hyaluronic acid, sulfated cartilage and silk fibroin to make composite cryogel, and to explore the feasibility of cryogel as alveolar bone repair. Natural biomaterials such as gelatin, chondroitin sulfate and hyaluronic acid are essential components in the extracellular matrix. Chondroitin sulfate contains disaccharide units of sulfate and carboxyl groups to which positively charged growth factors can attach, hyaluronic acid is a water-soluble polysaccharide widely distributed in the extracellular matrix, and many different functions of chondroitin sulfate come from their binding The ability of chondroitin sulfate to promote cell development and growth through a sulfate-dependent binding process to growth factors, through the fibroin and Hyaluronic acid and chondroitin sulfate are mixed to make injectable memory hydrogels. The main function of hyaluronic acid is to protect cells from damage during migration, and its concentration also affects cell migration. Make hyaluronic acid and cells form a bridge to make cells aggregate; and when the concentration is high, the bridge between the two will be interrupted to separate cells, so hyaluronic acid is important for cell aggregation, migration, regeneration and differentiation. influences. Therefore, the results of this experiment show that the addition of biomimetic materials does change and improve the deficiencies and applications of raw materials. The results of the study showed that the water content of gelatin as the substrate (group A) and the cryogel added with hyaluronic acid (group B), the water content of these two groups was more significant, and the swelling rate was also the same as that of groups A and B. The surging rate is also significantly increased in the A and B groups. The degradation rate is with the addition of gelatin, silk fibroin, hyaluronic acid and chondroitin sulfate. The four composite gels (group H) had lower degradation rates. The cytotoxicity test showed that all the materials were not toxic to cells, and the addition of silk fibroin and hyaluronic acid in the bone cell culture test showed that the addition of silk fibroin and hyaluronic acid helped the regeneration of cells, the most significant on the seventh day. The experimental results show that the addition of natural polymers does change and improve the deficiencies and applications of raw materials. The chondroitin sulfate-added groups all showed the ability to promote the regeneration and differentiation of osteocytes. The results of this study are expected to bring more options to the clinic.
參考文獻
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