含有矽奈米顆粒仿生支架用於臨界尺寸骨缺損組織再生之研究

Biomimetic Scaffold Containing Silicon Nanoparticles for Critical-Sized Bone Defect Regeneration

詹皓宇(Hao-Yu Chan)

指導教授 ： 宋信文

國立清華大學/工學院/化學工程學系/碩士(2021年)

摘要

臨界尺寸骨缺損(critical-sized bone defect)的治療至今仍是臨床骨科中面臨的難題，由於大量的骨質流失，結構不穩定及缺血導致傷處產生大量的ROS及發炎反應，對整體癒合進程產生不良影響。一般以自體骨移植或同種異體骨移植作為兩種主要的治療方式，其仍有許多限制如:取得體積有限、具感染風險或不具骨誘導性等。在本研究中，我們將礦化膠原蛋白(mineralized collagen)結合矽奈米顆粒(silicon nanoparticles)製備為仿生骨組織工程支架，並利用控制溫度梯度製備出具有放射狀排列的纖維結構。本研究分為三部份，在材料方面，我們合成出的礦化膠原蛋白表現出近似生物骨的組成，並透過比較結構差異、機械強度、孔隙度及骨傳導性等條件找到最適合動物實驗之支架配方，而摻雜於支架內的矽奈米顆粒能夠在體外釋放具抗發炎能力的氫氣及具骨誘導性之矽酸。在細胞實驗中，含有矽奈米顆粒之支架具有降低免疫細胞內ROS及促炎細胞因子的水平、促進成骨細胞分化及誘導細胞遷移至支架中心等效果。在動物實驗中，我們將支架植入大於臨界尺寸之小鼠顱骨缺損內，證實此含有矽奈米顆粒之骨仿生支架能夠有效提高新骨生成比例，顯示其應用於臨界尺寸骨缺損再生的潛力。

關鍵字

臨界尺寸骨缺損 ； 矽奈米顆粒 ； 仿生骨支架 ； 纖維排列

並列摘要

Treatment of critical-sized bone defects is still a difficult problem in clinical orthopaedics due to massive bone loss. Structural instability and ischemia result in high ROS and inflammatory response in the defect area, which adversely affects the overall healing process. Autograft or allograft are the two choices of treatment, which still have many limitations, such as limited volume acquisition, risk of infection, or lack of osteoinductive properties. In this study, we prepared mineralized collagen combined with silicon nanoparticles as a biomimetic bone tissue engineering scaffold, under controlled temperature gradients, to produce a radially aligned fibrous scaffold. The as-synthesized mineralized collagen, which exhibited a composition similar to that of biological bone, and compared the structural differences, mechanical strength, porosity, and osteoconductivity to find the most suitable scaffold formulation for animal experiments, while the silicon nanoparicles incorporated in the scaffold were able to release anti-inflammatory hydrogen and osteoinductive silicic acid. In cellular experiments, the silicon nanoparticles-containing scaffold could effectively reduce the levels of ROS and pro-inflammatory cytokines in immune cells, promote osteoblast differentiation, and induce cell migration to the scaffold center. In an animal study, we implanted the scaffold into a mouse cranial defect larger than the critical size and demonstrated that the silicon nanoparticles-containing bone biomimetic scaffold was effective in increasing the rate of new bone formation, demonstrating its potential for the repair of critical-sized bone defects.

並列關鍵字

critical-sized bone defect ； silicon nanoparticles ； biomimetic bone scaffold ； fiber alignment

參考文獻

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