生醫材料除了材料本身種類的選擇以外，材料表面之特性，例如電荷、成分、粗糙度和親水性功能都會影響到植體骨內固定，這些因素彼此具有交互作用的影響。目前最常被用於臨床植體的材料為純鈦及鈦合金，許多研究指出粗糙的鈦表面可以增加成骨母細胞的生物親和性，因此本研究使用純鈦金屬進行兩階段表面處理後評估其生物親和性。鈦植體最常使用的表面處理方式是在表面進行吹砂然後進行酸蝕（sandblasted, large-grit and acid etched, SLA）。SLA的製程可以在鈦植體表面製造出粗糙形貌以期達到鈦植體的機械固定特性及植體植入後長期穩定性。然而經過SLA處理的粗糙表面卻具有疏水的特性，但親水性表面對於細胞親和性卻有更好的貼附效果。因此在本研究中，純鈦經過表面處理後不僅保持了粗糙的形貌，而且還產生了親水性的表面特性。
本研究使用兩種電漿處理方法，直流電漿(Direct current, DC)和射頻(Radio frequency, RF)電漿來改善SLA處理過的疏水特性。兩種電漿處理建構了不同的功率範圍和不同含量的功能性氫氧基團。目前為止沒有文獻對於鹼性鈦-氫氧基團與細胞反應，骨結合強度或骨與植入物接觸面積之間的關係進行探討。因此本研究的目的是評估在粗糙表面製備含有豐富的兩性(Amphoteric)之功能性氫氧基團在活體外和動物實驗中的影響。
在經過SLA製程的鈦表面上產生功能性氫氧基。使用各種檢驗方式探討試片表面的形貌、粗糙度、親疏水性和化學成分。透過Enzyme-linked immunosorbent assay (ELISA)的吸光值測試評估經過1小時後，試片表面蛋白質吸附的含量。將MG63細胞在試片上培養3小時和24小時，使用掃描式電子顯微鏡觀察細胞形態。細胞培養1小時和24小時，以免疫螢光染色檢測細胞骨架。細胞培養1、7、14天後使用ELISA吸光值評估細胞增生和分化的表現。將24根鈦植體植入四隻紐西蘭大白兔的近側脛骨中，植入後4週和8週後，以扭力測試值(Removal torque values, RTV)和組織切片之新生骨與植體介面接觸面積(Bone-to-implant contact, BIC)的組織形態學分析進行討論。
實驗結果顯示，電漿處理不會改變微米級的表面形貌，並且電漿處理後的試片表面具有超親水的特性。DC和RF電漿處理組之間的親水性沒有顯著差異。藉由X光光電子能譜儀(X-ray Photoelectron Spectroscopy, XPS)分析表面組成，結果顯示RF電漿處理組之功能性氫氧基含量高於控制組和DC電漿處理組別。由於兩種電漿處理過後之試片表面兩性的氫氧基團豐富，將能促進蛋白質吸附和細胞貼附；RF電漿處理後的組別細胞形態呈現多觸手的形態，肌動蛋白(Actin)和黏著斑蛋白(Vinculin)表現量較高；與控制組相比，電漿處理也能促進細胞增生和分化能力，增生能力測試結果顯示RF-100的組別為控制組的1.5倍，分化能力測試結果顯示DC處理的組別及RF-50W均為控制組的兩倍，RF-100和RF-200為控制組的三倍。因此，結果顯示細胞的生物反應與兩性氫氧基團的總含量相關。RF-200W的扭力測試值RTV和骨與植體接觸面積BIC比例明顯高於其他組別，並具有統計上的差異（p < 0.05）。這表示較高的RTV和BIC值顯示RF電漿處理後的骨結合強度能有更好鍵結力。鹼性氫氧基團與RTV和BIC之間的關係也顯示出線性對應關係。骨破裂模式(Failure mode)可以提供植體與骨頭之間的鍵結界面之穩固特性評估。在骨破裂模式中，由於骨頭經過扭力測試後破裂的位置，我們提出了一個骨組織生長遵循三個方向機制的假說，並且RF電漿處理可以在4週和8週時促進骨癒合。

The surface properties such as charges, compositions, roughness, and hydrophilicity functional, play an important role in bone fixation and these factors are closely related to each other. Many studies reported that rough titanium surface could enhance the cell behavior of osteoblasts. In this study, commercial pure titanium is used for the following experiments. Nowadays the popular method to construct rough surface for clinical use is sandblasted, large-grit and acid etched (SLA). SLA method can fabricate a rough topography for mechanical fixation and long-term stability of titanium implant. However the rough SLA-treated surface exhibited hydrophobic property and cell affinity is favorable hydrophilic surface. In this study, the prepared titanium surface not only keeps rough topography but also produces a hydrophilic surface. This study used two kinds of plasma treatments including direct current and radio-frequency plasma to optimize the SLA-treated surface. The modification of plasma treatments creates respective power range and different content functional OH groups. There is no report in discussing the relationships between basic Ti-OH groups and cell responses, bone bonding strength or bone-to-implant contact. The aim of this study was to evaluate the effect of the amphoteric functional OH groups on the rough surface both in vitro and in vivo.
Functional hydroxyl groups were produced on a SLA-treated surface. The surface topography, roughness, wettability, and chemical composition were examined using various techniques. Protein adsorption was evaluated for 1h by ELISA. MG63 cells were cultured on specimens for 3h and 24h to observe cell morphology by SEM; cell cultured for 1h and 24h to examine the cytoskeleton by immunofluorescence image; cell cultured for 1, 7,14 days to evaluate cell proliferation and differentiation by ELISA. Twenty-four implants were inserted into the proximal tibia of four New Zealand white rabbits. The RTV and BIC of biological responses were measured in terms of histomorphometric analysis 4 and 8 weeks post-implantation.
The results show that the plasma treatments do not change the micron scale topography and plasma-treated specimens presented super hydrophilicity. There was no significant difference of wettability between DC and RF plasma treated groups. The surface composition were examined by XPS and the result showed that the functional OH content on the RF plasma-treated group was higher than the control and DC treatment groups. Because of the abundant amphoteric OH groups, the protein adsorption and cell attachment were promoted after plasma treatments; cell morphology in RF-plasma treated groups had more polygonal type and higher expression of actin and vinculin; cell proliferation and differentiation were also enhanced on plasma-treated groups compared to control. The cell responses have correlated to the total content of amphoteric OH groups. The RTV and BIC ratios of RF-200W were significantly higher than other groups (p< 0.05). It indicated higher RTV and BIC ratios represented better bone bonding strength after RF plasma treatment. The relationships between basic OH groups and RTV and BIC showed linear correspondence. The failure mode could provide the information about the interface fixation between implant and bone. The results of this study demonstrate that failure mode could provide the better understanding the bone-to-implant fixation. We proposed a hypothesis that the bone tissue growth is following the three-direction mechanism and RF-plasma treatment can help to enhance bone healing at 4 and 8 weeks.

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