骨骼具有複雜的層次結構以及自我再生的能力，但在臨界尺寸缺陷的情況下，正常骨骼的再生能力會嚴重受損，導致骨骼的不癒合。以骨組織工程的概念能夠有機會解決臨界尺寸的骨缺損相關之挑戰。目前在市場上可獲得的許多生物材料中，矽酸鈣（Calcium silicate，CS）為基材陶瓷因其多功能性和良好的生物活性而被人們所關注。在最近的十年中，科學家們試圖對CS進行改性或添加更多功用，以增強CS的生物活性。例如添加某些金屬離子促進骨頭的生長。據報導，將介孔奈米粒子添加到支架上加載藥物也可以增強支架對於骨的再生能力。而另一方面，以生物支架包覆細胞的是一種有前景的新穎方法，有機會加速組織工程和再生醫學工程技術上的開發及創新以製造出功能化之器官。然而，傳統的3D支架和載有細胞的水膠的製備方法仍然面臨許多困難和挑戰。本研究使用了一種新的生物列印技術和大量未充分利用的海洋副產物的概念來開發用於骨組織工程的新型支架。在本研究的第一部分中，將魚類所提取的明膠與生物活性陶瓷相結合用於骨組織工程，成功地透過光交聯製備了新型甲基丙烯酰化明膠聚合物水膠支架（Fish gelatin methacrylate scaffold，FG），並且將其與摻有鍶的矽酸鈣（Strontium-doped calcium silicate，SrCS）混合列印之，製備含生物陶瓷之水膠支架（FGSr），後續將評估其機械性質、物化性分析、降解特性。此外也在列印過程中將幹細胞摻混入材料一同列印，再將列印後的支架經過體外培養，在不同時間點進行細胞生物相容性、Live/dead細胞染色、鹼性磷酸酶以及骨礦化分析。第二部分的主要目的是進一步以FG為列印基材，並將將骨形態發生蛋白-2（Bone morphogenic protein-2，BMP-2）搭載入摻有鍶的介孔洞矽酸鈣（meso SrCS）結合，期望能夠藉由介孔洞陶瓷粉末，來延長BMP-2釋放的時間，並且同樣使用光固化的列印過程將上述材料製備成三維多孔支架，後續將評估其組成分析、機械強度、以及BMP-2釋放效果。後續也將細胞與材料混合列印，並且測試細胞的生物相容性以及成骨分化相關的基因表現能力。我們也預期這樣的設計，對於骨組織再生的效果將能夠大幅提升，並且評估未來能在臨床上的使用可行性。

Bone has a complex hierarchical structure with the capability of self-regeneration. In the case of critical-sized bone defects, the regeneration capabilities of normal bones are severely impaired, thus causing non-uniform healing of bones. Therefore, bone tissue engineering has since emerged to solve problems relating to critical-sized bone defects. Amongst the many biomaterials available on the market, calcium silicate-based (CS) cements have garnered huge interest due to their versatility and good bioactivity. In the recent decade, scientists have attempted to modify or functionalize CS cement in order to enhance the bioactivity of CS. Reports have also been made, so that the addition of mesoporous nanoparticles onto scaffolds could enhance the bone regenerative capabilities of scaffolds. On the other hand, cell-encapsulated bioscaffold is a promising and novel method to allow for the fabrication of live functional organs for tissue engineering and regenerative medicine. However, traditional fabrication methods of 3D scaffolds and cell-laden hydrogels still face many difficulties and challenges. This study uses 3D fabrication technique and the concept of recycling of an unutilized resource to fabricate a novel scaffold for bone tissue engineering. So, in the part I of this study, fish-extracted gelatin was incorporated with bioactive ceramic for bone tissue engineering, and with this, we successfully fabricated a novel fish gelatin methacrylate scaffold (FG). Besides, we further incorporated strontium Sr-doped calcium silicate powder (SrCS) into methacrylated gelatin for the preparation of ceramic-contained hydrogel 3D scaffold (FGSr) via photo-crosslinking. And the main object in part II was to reuse gelatin from fish wastes and use it to combine with bone morphogenetic protein (BMP)-2 and meso SrCS to create a novel BMP-2-loaded, hydrogel-based mesoporous SrCS scaffold (FGSrB) and to evaluate its composition, mechanical strength and biological functions.
Keywords: 3D printing, Cell-laden scaffold, Calcium silicate, Strontium, BMP-2

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