Study on Alloy Development and Mechanical Properties of Bio-medical Ti-alloys

　　本研究依據人工關節植入件之性質要求，開發具低楊氏係數、高強度及生物相容性之Ti合金材料。首先針對現今應用最普遍之生醫用Ti合金，Ti-6Al-4V，探討各種加工製程對於合金內部及表層組織之影響。經切削、銑削及研磨後，其內部顯微組織基本上不發生任何變化，而表層組織則存在一細化層（內層）及一氧化層（外層），其中細化層厚度約1~2μm，氧化層厚度小於0.2μm。針對熱滾軋而言，在ㄐ洷]→β相變態溫度（957℃~997℃）以上進行滾軋時（如：1000℃及1100℃），晶粒有明顯粗化現象，而在變態溫度以下進行滾軋時（如：900℃），晶粒則會變細。經熱滾軋後，試片之表面會形成一表層組織（氧化層），該表層組織在人體體液下為一耐腐蝕之組織，且對細胞活性並無影響。鑄造後之晶粒較原素材粗大，表層具有一　　This study attempts to develop Ti-alloys with elastic moduli that approach that of human bone, high strength and biocompatibility. Among the implant materials currently used, Ti-6Al-4V is the most widely used one for orthopedic application. First, This study examines the effects of various manufacturing processes, including machining (cutting, milling and grinding), hot rolling and casting, on the microstructure- both bulk and superficies of the biomedical grade Ti-6Al-4V alloy. The results indicate that after machining the microstructure of the bulk remains unchanged, while an oxide layer is evident at the surface; next to the outer-most layer, a very fine structure layer can be observed. Regarding the rolling process, at the rolling temperature of 900oC, the specimens show a slightly refined structure, whereas at 1000oC and 1100oC, they show a substantial coarse grain structure. The coarse structure of the 1000oC-rolled specimens can be refined substantially by re-rolling at temperatures lower than 957oC, which is the目 錄 誌謝…………………………………………….…………….………I 摘要…………………………………………….…………….………II 英文摘要…………………………………………….…………….………IV 目錄………………………………………………….…………….………VI 表目錄……………….………...…………………….…………………IX 圖目錄…….………………………………………………………….…..X 第一章 緒論……………………………………………………...………1 第二章 文獻回顧………………………………...….……….……………6 2.1 生醫材料的定義…...………………….………….…………6 2.2 近代金屬生醫材料的發展………………………..………….6及……………………………….…………10 2.3 鈦合金的特性及分類……………………………….……...9 2.4 合金元素的影響…...………………….………….……10 2.5 楊氏係數…………...………………….………….……11 2.5.1 楊氏係數測量方法...…………...………………………11 2.5.2 影響楊氏係數之因素……………………………………12 第三章 加工製程對於Ti-6Al-4V顯微組織及表層性質之影響...….19 3.1 前言…………………………………….……………………19 3.2 實驗方法………………………………..………………...20 3.2.1 原素材之成份分析……..…………………………….20 3.2.2. 加工製程………………………………………………20程 程………………………………………………….79 造………………………………………………..79 3.2.2.1 切削、銑削及研磨…………………………………….20磨………………………………………………81 3.2.2.2 滾軋………………………………………………..….20 3.2.2.3 鑄造…………………………………………………….20 3.2.3 顯微組織分析…..……………………………………….21 3.3 結果……………………………………………………………21 3.3.1 原素材之顯微組織及熱分析………………………….21 3.3.2 加工製程對顯微組織之影響………………………….22 3.3.2.1 切削、銑削及研磨…………………………………….22磨………………………………………………81 3.3.2.2 滾軋……………………………………………...…22 3.3.2.3 鑄造…………………………………………………..24 3.4 討論…………………………………….…………………24 3.5 結論…………………………………….……………………25 第四章 Ti-Nb二元合金之成份/顯微組織與機械性質之間的關係…46 4.1 前言…………………………………….…………………46 4.2 實驗方法………………………………..………………..47 4.2.1 合金配置及試片準備………………………………47 4.2.2 成份分析……………………………………………48 4.2.3 金相分析……………………………………………48 4.2.4 X光 繞射分析(XRD analyses)…………………..48 4.2.5 穿透式電子顯微鏡分析(TEM analyses)………..48 4.2.6 拉伸試驗……………………………………………49 4.3 結果與討論……………………………………………….49 4.3.1 顯微組織分析…………………………………………49 4.3.2 X光 繞射分析(XRD analyses)……………………49 4.3.3 穿透式電子顯微鏡分析(TEM analyses)…………50 4.3.4 楊氏係數………………………………………………51 4.3.5 抗拉性質………………………………………………52 4.3.6 斷面觀察……………………………………………52 4.4 結論…………………………………….……………..……53 第五章 Ti-40Nb-xHf合金之顯微組織及機械性質………………71 5.1 前言…………………………………….…………………71 5.2 實驗方法………………………………..…………………72 5.2.1 合金配置及試片準備…………………………………72 5.2.2 成份分析………………………………………………72 5.2.3 金相分析………………………………………………72 5.2.4 X光 繞射分析(XRD analyses)……………………72 5.2.5 穿透式電子顯微鏡分析(TEM analyses)…………72 5.2.6 拉伸試驗……………………………………………...72 5.3 結果與討論……………………………………………….73 5.3.1 顯微組織分析………………………………………73 5.3.2 X光 繞射分析(XRD analyses)…………………..73 5.3.3 穿透式電子顯微鏡分析(TEM analyses)………..73 5.3.4 抗拉性質……………………………………………73 5.4 結論…………………………………….……………………74 第六章 Ti-30Nb-1Fe-yHf合金之顯微組織及機械性質………….84 6.1 前言…………………………………….……………………84 6.2 實驗方法………………………………..………………..….85 6.2.1 合金配置及試片準備…………………………………85 6.2.2 成份分析………………………………………………85 6.2.3 金相分析………………………………………………85 6.2.4 X光 繞射分析(XRD analyses)……………………85 6.2.5 穿透式電子顯微鏡分析(TEM analyses)…………85 6.2.6 拉伸試驗……………………………………………...85 6.3 結果……………………………………………………………86 6.3.1 Ti-30Nb-xFe合金之抗拉性質…………………………..86 6.3.2 顯微組織分析…………………………………………86 6.3.3 X光 繞射分析(XRD analyses)……………………86 6.3.4 穿透式電子顯微鏡分析(TEM analyses)…………87 6.3.5 抗拉性質………………………………………………87 6.4 討論…………………………………….……………………88 6.5 結論…………………………………….……………………91 第七章 總結論……………………………………………..………..107 參考文獻………………………………………………..………..……113 著作…………………………………………………..………..……12

Sex Differences in Conscious Sedation During Upper Gastrointestinal Panendoscopic Examination

Sex differences in response to noxious stimuli or analgesia have been demonstrated. We investigated sex differences in conscious sedation during upper gastrointestinal panendoscopic examination with regard to drug dose and entropy scores. Methods: We investigated sex differences in 30 men and 30 women who were undergoing conscious sedation during upper gastrointestinal panendoscopic examination. The drug mixture was prepared as 5 mg midazolam plus 1 mg alfentanil diluted with normal saline to a volume of 10 mL. An initial injection of 4 mL was followed by an additional 1 mL every 1 minute, until the modified Observer Assessment of Alertness and Sedation (OAAS) rating scale was ≤ 3 when the panendoscope was inserted. Further injection was allowed thereafter. Entropy values, including state entropy (SE) and response entropy (RE), were monitored from baseline to full recovery. Results: The volume of mixture needed to achieve an OAAS score of ≤ 3 was significantly lower in men than in women (4.4 ± 0.7 mL vs. 4.8 ± 0.8 mL, p = 0.034). The initial drug demand was not significantly influenced by age, body weight, or body height. The RE and SE values at the time of panendoscope insertion were not significantly different between men and women. The total volume for men was also significantly lower than that for women (5.7 ± 1.1 mL vs. 6.5 ± 1.4 mL, p < 0.01). The lowest RE and SE values during the procedure were not significantly different between men and women. Conclusion: Women need more analgesic agents than men during panendoscopic examination. There was no significant difference between men and women with regard to anesthetic depth and response to noxious stimuli, as revealed by similar SE and RE values

Glucosamine Enhancement of Learning and Memory Functions by Promoting Fibroblast Growth Factor 21 Production

Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN’s activation of the NF-κB, Akt, p38, and PKA/CREB pathways

Orbital complications of paranasal sinusitis in Taiwan, 1988 through 2015: Acute ophthalmological manifestations, diagnosis, and management.

Paranasal sinusitis is widespread and can lead to orbital complications, blindness, and death. However, the correlation between ophthalmological findings and disease staging remains unclear. This study aimed to investigate the staging, acute ophthalmological manifestations, diagnosis, management, and outcomes of orbital complications of paranasal sinusitis during a 27-year period.We retrospectively reviewed the medical records of all patients with orbital complications of paranasal sinusitis hospitalized at the National Cheng Kung University Hospital, a medical center in Taiwan during 1988-2015. Sex, age, symptoms, history, ophthalmological findings, laboratory and imaging findings, treatments, and outcomes were analyzed by staging.Eighty-three patients aged 9 days to 80 years had stage I (preseptal cellulitis, n = 39 patients), II (postseptal orbital cellulitis, n = 8), III (subperiosteal abscess, n = 16), IV (orbital abscess, n = 8), or V (intracranial involvement, n = 12) complications. Peak incidences occurred in patients aged 0-19 and 60-69 years. Chronic sinusitis and diabetes mellitus were common preexisting diseases. Extraocular movement limitation and proptosis predicted postseptal (stage II or more) involvement. The likelihood of elevated intraocular pressure increased with stage. Reduced visual acuity and presence of relative afferent pupillary defect indicated consideration of magnetic resonance imaging to investigate possible intracranial extension. Ipsilateral maxillary (81.7%) and ethmoidal (75.6%) sinuses were the most common sources of infection, and the most frequently implicated pathogens were coagulase-negative Staphylococcus spp. (25.3%) and Staphylococcus aureus (20.5%). All patients received intravenous antimicrobial therapy (multi-drug therapy in 88.0%), and 55.4% underwent surgery, most commonly endoscopic sinus surgery. One (1.2%) diabetic man with stage V complications died of fungal sinusitis with intracranial invasion. Five (6.0%) patients, all stage V, lost vision despite intensive treatment. The average length of hospital stay was 13.8 days (range 2-72 days), and significantly longer stays were associated with stages II-V as compared to stage I.Orbital infection originating from paranasal sinusitis can cause vision loss and death due to intracranial extension. Acute ophthalmological findings predict staging and prognosis. Cooperative consultation between ophthalmologists, otorhinolaryngologists, and neurologists is essential. Urgent diagnostic studies and aggressive antimicrobial therapy are indicated, and surgery should be considered

Treatments and outcomes in 83 patients by stage of orbital complications of sinusitis.

<p>Treatments and outcomes in 83 patients by stage of orbital complications of sinusitis.</p

Characteristic findings of each stage of sinusitis-related orbital complications determined via computed tomography (CT) or magnetic resonance imaging (MRI).

<p><b>(A)</b> Stage I, preseptal cellulitis (arrow) on an axial CT image. <b>(B)</b> Stage II, orbital cellulitis (arrow) on an axial CT image. <b>(C)</b> Stage III, subperiosteal abscess (arrow) on a sagittal CT image. <b>(D)</b> Stage IV, orbital abscess (arrow) with a tiny air bubble on an axial CT image. <b>(E and F)</b> Stage V, cavernous sinus thrombosis (arrow) on a coronal contrast-enhanced T1-weighted MRI, and focal cerebritis (arrowheads) on a coronal contrast-enhanced T1-weighted MRI and an axial T2-weighted MRI. * Ethmoidal sinusitis. † Artifact due to metal material. Dashed lines: Proptosis in one eye compared with the fellow eye.</p

Percentages of acute ophthalmological findings in 83 patients by stage of orbital complications of sinusitis.

<p>The increasing incidences of acute ophthalmological findings by stage were categorized into three patterns. “EOM limitation” and “proptosis” substantially increased from stage II, and thereafter were sustained at high percentages during stages III–V. “IOP > 23 mmHg” increased steadily by stage. The incidences of “VA change” and “RAPD present” substantially increased at stages IV and V respectively. <b>Abbreviations:</b> EOM, extraocular movement; IOP, intraocular pressure; RAPD, relative afferent pupillary defect; VA, visual acuity.</p

Percentages of sinuses involved in 83 patients by stage of orbital complications of sinusitis.

<p>There was a trend of a positive association between stage and the number of sinuses involved. The most frequently involved numbers of sinuses were 1 for stages I and II, 3 for stage III, and 4 or more for stages IV and V.</p

Age distribution of 83 patients with orbital complications of sinusitis.

<p>Age peaked at 0–9 years, followed by 10–19 years. An additional peak occurred at 60–69 years.</p