臺灣博碩士論文加值系統

目前臨床對於較大範圍或未痊癒的骨缺陷，仍然在尋求最佳的解決方式。市面上骨植材大多面臨無法針對創傷設計形狀以及容易脫落的問題。雖然透過近年來發展的雷射積層熔融(SLM)技術，可以設計製造出複雜的三維(3D)結構，但是如何增進骨植材與活體組織相容性，進而解決骨植材鬆脫仍是一大問題。本研究是針對雷射積層熔融製成的Ti6Al4V合金(SLM-produced Ti6Al4V)，藉由金屬表面奈米處理與表面化學修飾進行生物相容性改質，使改質後的SLM-produced Ti6Al4V具骨引導性(osteoconduction)及骨誘導性(osteoinduction)，以利活體植入治療。本實驗利用陽極氧化技術（Anodic oxidation, AO），將經電解拋光的SLM-produced Ti6Al4V合金，置於含氟乙二醇電解液中，通以10 V電壓之直流電，在60°C下處理10分鐘進行表面奈米結構處理。再以化學小分子作奈米結構的表面化學改質，最後披覆氫氧基磷灰石(HA) 24小時。陽極氧化處理Ti6Al4V試片，可觀察表面均勻分佈、孔徑大小一致的二氧化鈦管柱，其平均管徑大小約為14.5±2.7 nm。表面化學修飾後在二氧化鈦管柱表面形成一層尾端帶有胺基(-NH2)的自組裝薄膜。將處理過的SLM-produced Ti6Al4V進行C2C12細胞培養。藉由螢光染色顯微鏡觀察細胞，並量化細胞生長情形以評估材料修飾前後的生物相容性。表面改質可使細胞更容易生長與貼附，增進生物相容性。另外，未處理與表面處理後SLM-produced Ti6Al4V圓柱，分別植入紐西蘭大白兔的遠端股骨做活體實驗。本研究之表面與適當的表面修飾與改質，披覆HA薄膜於經金屬表面奈米處理與表面化學修飾的SLM-produced Ti6Al4V合金，其奈米結構仍然存在。且奈米結構、-NH2與HA的共同作用可有效提高Ti6Al4V生物相容性。

There is no optimal solution for the treatment of large or non-healing bone defects to date. All currently available therapies have important drawbacks; for example, the bone implants available today are mostly confronted with the problem of designing shape for wounds and falling off easily. The technique of selective laser melting (SLM) is capable of producing intricately designed three-dimensional (3D) structure. However, how to create a biocompatible interface between those SLM-produced bone implants and living tissues remains a challenge. This study aims at the creation of biocompatible interface on the surface of SLM-produced Ti6Al4V scaffold for implantation. Since there are semi-molten powder particles on the surface of SLM-produced Ti6Al4V, those particles are abraded and finally result in tissue inflammation and apoptosis. Here, Ti6Al4V specimens were cleaned in ultrasonic bath to remove most of the particles and followed by electrolytic polishing process in sulfuric acid/methanol solution at 8 volts under the low temperature to effectively improve the surface flatness. Then, the technique of anodic oxidation (AO) was applied to create surface nanostructure on the flat SLM-produced Ti6Al4V in fluorine-containing ethylene glycol electrolyte at 10 volts and 60°C for 10 min to obtain uniform titania nanotubes (TNTs). The samples were chemically modified in 1% 3-aminopropyltrimethoxysilane (APTMS) ethanolic solution for 2 h. After that, the APTMS-modified TNTs were immersed in the simulated body fluid (SBF) for 24 h to complete the surface modification process of SLM-produced Ti6Al4V. The TNTs were observed with an average diameter of about 14.5±2.7 nm on the surface of SLM-produced Ti6Al4V alloys. Electrolytic polishing and anodization can effectively remove the residual particles caused by SLM process. Self-assembled layer with the end of amine functional group was formed on the surface of the TNTs. The APTMS-modified TNTs specimens were further coated a thin film of hydroxyapatite (HA), which could improve the abilities of osteoconduction and osteoinduction with intrinsic bone tissue. The C2C12 cells and their differentiated ones were used to evaluate the in vitro biocompatibility tests. Highly ordered TNTs array effectively improved the surface roughness and increased the surface area. The unmodified and modified SLM-produced Ti6Al4V cylinders were implanted into the distal femur of New Zealand white rabbit for in vivo observation. The nanostructures were still obvious on the surface of anodized and chemically modified SLM-produced Ti6Al4V after HA coating. The synergistic effects of nanostructures, -NH2 and HA could improve biocompatibility of SLM-produced Ti6Al4V.

1. Introduction 1
1-1 Selective Laser Melting (SLM) Technology 1
1-2 Medical Bone Implants 1
1-3 Surface Modification on Ti Alloys 4
1-4 Motivations and Aims 5
2. Materials and Methods 7
2-1. Nanostructure Fabrication 7
2-2. Surface Modification 10
2-3. Characterization of Materials 11
2-4. In Vitro Biocompatibility 12
2-5. In Vivo Test 14
2-6. Statistical Analysis 15
3. Results 15
3-1. Surface Characterization 15
3-2. In Vitro Biocompatibility 25
3-3. In Vivo Experiment 30
4. Discussion 32
4-1. Experiment Discussion 32
5. Conclusion 37
6. Reference 38

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