多巴胺改質生醫材料應用於關節軟骨與硬骨組織工程

Abstract

鑑於軟骨自我修復以及大型骨頭創傷再生能力上的限制，組織工程的治療對於軟骨與硬骨的修復相對於獲取組織以用於傳統的移植手術來說，是另一種更好的選擇方法。使用具有生物活性表面的仿生材料已被廣泛應用於軟骨與硬骨組織工程。在本研究中，我們希望藉由多巴胺修飾的生醫材料能促進細胞的增生與功能，並且對於軟骨與硬骨組織工程上的應用能具有良好的潛力。 在本研究中，我們藉由將生醫材料聚胺基甲酸酯(PU)、聚己內酯(PCL)、聚乳酸-甘醇酸(PLGA)與聚左旋乳酸(PLLA)沉浸於鹼性(pH=8.5) 的多巴胺溶液以塗佈在各種高分子膜與支架的表面上做為軟骨與硬骨組織工程上的應用。多巴胺修飾在各種高分子表面的時間只進行幾秒到數分鐘之久，接著再分別將軟骨或骨母細胞植佈在這些不同多巴胺塗佈時間的材料表面上。在含有血清培養基的環境下，與未經多巴胺修飾的材料相比，多巴胺塗佈在這些材料表面的時間皆僅僅需要幾秒到數分鐘的時間就足以很明顯的促進軟骨及骨母細胞的貼附及增生。多巴胺修飾的三維PU支架不僅能促進軟骨細胞增生，還可增進細胞外間質的合成包含糖胺聚糖(GAGs)的沉積與膠原蛋白(collagen)的分泌。此外，經由多巴胺修飾的PCL膜除了促進骨母細胞增生外，還能增進細胞基質的礦化，不過多巴胺並無法有效的增進鹼性磷酸酶(ALP)的活性。 本研究成功以簡單有效的方法製備具有生物活性表面的多巴胺修飾材料，並能促進軟骨與骨母細胞的貼附、增生與功能。因此，多巴胺在軟骨與硬骨組織工程上的應用能具有良好的潛力。 關鍵字：多巴胺、生醫材料、軟骨組織工程、硬骨組織工程

Due to the limited repair capabilities of cartilage and regeneration of large traumatic bone defects, tissue-engineered therapies for cartilage or bone repair are the alternative strategy to harvested tissues for the conventional transplantation. The use of biomimetic biomaterials with bioactive surfaces has been considered for the application of cartilage and bone tissue engineering. We hope that the dopamine-deposited biomaterials can promote cell proliferation, function, and be good candidates for cartilage and bone tissue engineering. We use a method to coat the dopamine on various films or scaffolds including PU, PCL, PLGA and PLLA by simple immersion in the alkaline dopamine solution (pH= 8.5). The time required for dopamine modification on various polymer surfaces were only from few seconds to several minutes. Chondrocytes and osteoblasts were cultured on the surfaces with different dopamine coating times. Only few seconds to minutes was sufficient for the coating time of dopamine modification on various surfaces compared with unmodified surfaces to significantly facilitate the cell adhesion and proliferation for both chondrocytes and osteoblasts under serum medium condition. The dopamine-deposited 3-D PU scaffolds are able to augment not only chondrocytes proliferation but also synthesis of extracellular matrix including the GAGs deposition and collagen secretion. Furthermore, it was displayed that the dopamine-deposited PCL films are able to promote not only osteoblasts proliferation but also the matrix mineralization although the dopamine does not improve the ALP activity on PCL films. Through this research, a simple and efficient strategy to produce the dopamine-modified biomaterials with bioactive surfaces can enhance both chondrocytes and osteoblasts for cell adhesion, proliferation and function. Hence, dopamine may be the good candidate for the application of cartilage and bone tissue engineering. Key words: dopamine; biomaterials; cartilage tissue engineering; bone tissue engineering