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研究生:蔡冠宇
研究生(外文):Guan-Yu Jiang
論文名稱:軟硬骨複合式組織支架快速成型技術開發與應用研究
論文名稱(外文):Development and Application of Rapid Prototyping Technologies for Osteochondral and Bone Tissue Scaffold
指導教授:李明義李明義引用關係
指導教授(外文):Ming-Yi Lee
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫療機電工程研究所
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:203
中文關鍵詞:組織工程支架雷射燒結丙烯酸甲酯如鹽析法幾丁聚醣連結性調整器快速成型
外文關鍵詞:tissue engineerscaffoldslective laser sinteringrapid prototyping.alreadydesignsystem
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中文摘要
利用組織工程製作人造膝關節,須完成具有股骨、脛骨及半月板等三種關節結構元件之多孔性支架,而目前支架製作大多採用模具成型法(如鹽析法、氣體發泡法、膜積層法等),無法完全掌控支架內孔洞結構(大小、密度) 及孔洞間連結性,其中股骨、脛骨屬於硬骨組織結構且具有幾何複雜外形,無法由模具成型法製作成形。根據文獻指出,利用雷射燒結法製作組織支架因其具有良好機械強度結構,不需以支撐架輔助,所以可克服幾何複雜外形製作之問題;另外,半月板屬於軟骨組織,如以模具成型法製作,製程中需使用有機溶劑將填充物(氯化鈉)析出,易造成孔洞分布不均與孔洞間相互聯結不良等問題。再者,若有機溶劑殘留支架上會造成細胞貼附生長困難。
爰此,本研究為了克服上述製作多孔性支架組織之問題,研究工作分為多孔性支架孔洞設計模組開發、雷射燒結快速成型機改良設計及多種生醫材料多孔性結構組織支架之實體製作等三部份。在多孔性支架孔洞設計模組開發方面,本研究係利用Pro/Engineer及Visual Basic工具軟體進行組織支架多孔性單元結構設計模組及組織支架力學分析模組之開發;在雷射燒快速成型機改良設計方面分為軟、硬體設計兩項,在軟體部份係利用CpoyCAD之巨集指令並配合Visual Basic工具軟體進行單層疊代切層/連續切層模組之人機介面開發、利用PowerMILL之巨集指令並配合Visual Basic工具軟體進行單層燒結路徑規劃模組之人機介面開發等;在硬體部份,主要係利用Pro/Engineer工具軟體進行材料預熱溫控系統及粉末填充刮板機構之設計;材料預熱溫控系統之主要機構元件包括預熱保溫蓋、加熱器、溫控調整器、熱循環風扇、粉末回收槽等。本系統為了驗證所開發快速成型實驗機台雷射燒結製作組織支架之可行性與實用性,也利用粒徑分析儀與光學顯微鏡分析兩種廠牌骨水泥(ZIMMER及Howmedica)、氫氧基磷灰石(hydroxyapatite或簡稱HA)、幾丁聚醣 (poly-β-1,4-glucosamine)、聚甲基丙烯酸甲酯(Poly methyl-methacrylate或簡稱PMMA)、磷酸鹽三鈣(β-tricalcium phosphate或簡稱TCP)等六種不同生醫原材料及燒結製作完成支架之顆徑大小、利用骨水泥燒結11種不同孔洞型式之雙層結構組織支架、製作不同孔隙率10%、20%、30%、40%等四種單層結構之組織支架、利用骨水泥測試本機台燒結製成參數(雷射功率) 對燒結完成支架品質之影響,並製作0.1mm至0.8mm不同線距之行列式均佈孔洞單層支架、利用骨水泥進行材料預熱燒結測試,預熱溫度為50℃、60℃、70℃、80℃等四種、骨水泥與類似人體骨骼之氫氧基磷灰石生醫材料混合燒結測試,燒結完成時也利用高倍速聚焦相機、光學顯微鏡及掃瞄式電子顯微鏡進行生醫原材料燒結製作完成支架之巨觀與微觀結構分析、利用骨水泥製作人體股骨及半月板立體組織支架。
本研究已改良設計完成一套雷射燒結生醫材料快速製作多孔性支架組織之設備,經由實驗證明本系統能成功地製作出多孔性組織支架。另外,本研究所完成之多孔性支架孔洞設計模組可依臨床需要之孔隙率,透過單元孔洞陣列設計產生多孔性立體支架孔洞型式,並由支架CAD設計檔轉換成STL檔案格式供快速成型機使用。本研究實驗已確認了所開發之多孔性支架孔洞設計模組及雷射燒結快速成型機,可克服現今組織支架設計與製作之問題,未來將可發展成為一套電腦輔助設計與快速製作多孔性組織支架之整合技術。
Abstract
Utilize the tissue engineer to make artificial knee joint, Must finish the scaffold of three kinds of joint structure components , such as femur , shin bone and meniscus,the traditional method of making tissue scaffold is through molding(solvent casting/ emulsion freeze drying/ gas foaming). Can't control the question of linking with hole of the hole structure of the scaffold (the size , density ). The femurs , shin bones are that the hard bone tissue has complicated appearance of geometry, can't do with the mold . While studying by Jessica M. Williamsa , utilize the laser sintering process scaffold have good mechanical intensity, do not need the support frame, so can solve the problem of the complicated appearance of geometry . In addition, the meniscus is organized by the cartilage, make with mould shaping law , will use organic solvent dissolve the packing material (sodium chloride ) out , will cause and bind the question such as being bad each other among Kong Dong's all kinds of inequality and hole. It will influence cells to grow on the scaffold that the solvent remains. Incomplete shortcoming that the laser sintering process will produce the hot stress centralizedly and frit.

So, utilize laser sintering make the artificial hard bone support of knee joint and cartilage support. Except that this, will do the two phase compounding type scaffold that the soft hard bone cell turns into in experiment. Can let the Cartilage tissue , hard bone tissue cells to grow and open time , will have cartilages to organize the scaffold covered to make the human skeleton structure. This research is divided into softly / hardware two partly, Have already developed and organized the optimization unit structure software design of the support in the part of the software, technology of planning etc. that organize support mechanics and analyse software design , single layer and cut story , single story in the route totally totally . Part develop temperature-controled system already in hardware, working content its for is it is it overlay to keep warm to preheat, heater , temperature-controled adjuster , thermal cycle fan , powder retrieve trough ,etc. In order to verify the feasibility and practicability of the experiment machine platform and technology developed, will born and cure material characteristic analysing , testing , research of testing , organizing the support entity to make etc. that the rate of hole controlled frit that the modelling of 11 kinds of holes in a utensil frit .
指噵教授推薦書..........................................................................................
口試委員會審定書......................................................................................
授權書.......................................................................................................iii
致謝...........................................................................................................iv
中文摘要....................................................................................................v
英文摘要..................................................................................................vii
目錄...........................................................................................................ix
表目錄....................................................................................................xvii
圖目錄...................................................................................................xviii
第一章 研究背景、動機與目的................................................................1
1.1 研究背景.....................................................................................1
1.2 研究動機.....................................................................................8
1.3 研究目的.....................................................................................9
1.3.1組織支架最佳化單元結構軟體設計技術開發..............10
1.3.2 軟硬骨組織支架雷射燒快速成型相關製作技術開發
.......................................................................................10
1.3.3 組織支架實體製作及生物相容性評估.......................11
1.4 論文架構.................................................................................12
第二章 文獻回顧....................................................................................13
2.1 生醫材料...................................................................................13
2.1.1 明膠(gelatin type A, sigma,G-2500,Approx. 300 Bloom) ...........................................................................15
2.1.2 膠原蛋白(collagen).......................................................16
2.1.3 幾丁聚醣[ poly(β-1,4- glucosamine)] ..........................17
2.1.4 聚乳酸(poly-L-lactic acid,PLLA) ..............................18
2.1.5 聚甘醇酸 (polyglycolide,PGA) ..................................18
2.1.6 聚乳酸-聚甘醇酸( poly-D,L-lactide-co-glycolide , PLGA ) ...........................................................................18
2.1.7 聚己內酯(polycaprolactone,PCL) ..............................19
2.1.8 氫氧基磷灰石(hydroxyapatite;HAP) .........................19
2.1.9 聚甲基丙烯酸甲酯(polymethylmethacrylate, PMMA) .
........................................................................................19
2.1.10 膠原蛋白(collagen type I)..........................................20
2.1.11 海藻酸鈉(Sodium Alginate).......................................20
2.2組織工程支架結構設計與分析技術.........................................20
2.3傳統組織工程支架製作技術相關文獻.....................................25
2.3.1 溶劑鑄造/鹽析法( solvent casting / particulate leaching ) .................................................................................25
2.3.2 冷凍乾燥法( emulsion freeze drying ) ........................26
2.3.3 相分離法( phase separation ) ......................................27
2.3.4 氣體發泡法( gas foaming ) ..........................................27
2.3.5 纖維鍵結法( fiber bonding ) ........................................29
2.3.6 膜積層(Membrane Lamination) .................................30
2.3.7 擠壓成形(Extrusion) ....................................................31
2.4 快速成型組織支架製作技術.................................................. 32
2.4.1 三維噴印(3-Dimension Printing;3DP).......................32
2.4.2 熔融層積成型(Fused Deposition Modeling;FDM)
.......................................................................................33
2.4.3 瑞士聯邦大學 Microstereolithography 快速成型
機....................................................................................34
2.4.4 雷射燒結快速成型(Selected Laser Sintering ;SLS) ...............................................................................35
2.4.5 低溫熔融層積成型(Low-temperature deposition manufacturing;LDM)............................................................36
2.4.6 3D bioplotter...................................................................38
2.4.7 Precision extruding deposition (PED) .........................39
2.5 理論基礎...................................................................................41
2.5.1 適合骨細胞生長之結構空間理論.................................41
2.5.2 孔隙率計算理論.............................................................43
2.5.3 結構分析理論.................................................................45
2.5.3.1作用力與反作用力.......................................................47
2.5.3.2內力與應力...................................................................47
2.5.3.3 平面應力......................................................................48
2.6 文獻總結...................................................................................50
第三章 組織支架最佳化單元結構軟體設計技術開發........................51
3.1 Pro/Engineer、Automation Gateway及Visual Basic開發模組安裝說明..............................................................................52
3.2 組織支架最佳化單元結構軟體設計技術開發.......................59
3.2.1 組織支架單元結構設計模組開發.................................61
3.2.2單元孔洞陣列模組開發..................................................66
3.2.3組建模組..........................................................................70
3.2.4 組建交集模組.................................................................76
3.3 孔隙率計算模組...................................................................... 80
3.4 本章總結...................................................................................85
第四章 組織支架結構力學分析軟體設計技術開發............................86
4.1組織支架結構力學分析軟體設計技術開發.............................86
4.2分析說明模組.............................................................................88
4.3參數設定模組.............................................................................89
4.3.1設定材料係數..................................................................89
4.3.2 設定力(力距)之負載.....................................................90
4.3.3 設定邊界條件.................................................................92
4.4運算模組.....................................................................................94
4.4.1 結合參數進行運算........................................................ 94
4.4.2 查詢運算結果................................................................ 95
4.4.3 執行分析........................................................................ 96
4.5 呈現分析結果模組...................................................................98
4.5.1 雲紋-應力-VON Mises..................................................98
4.5.2向量-應力-VON Mises....................................................99
4.5.3 呈現動畫分析.................................................................99
4.6 分析結果存檔模組.................................................................100
4.6.1 儲存分析檔...................................................................100
4.6.2 存JPG格式..................................................................100
4.6.3 存MPEG格式(動畫) ..................................................101
4.7 本章總結..........................................................................102
第五章 軟硬骨組織支架雷射燒快速成型相關製作技術開發..........103
5.1 硬體精進與開發.....................................................................103
5.1.1 生醫材料預熱保溫蓋製作...........................................108
5.1.2 溫控調整器...................................................................109
5.1.3 加熱器...........................................................................111
5.1.4 粉末回收槽...................................................................112
5.1.5 刮板結構.......................................................................113
5.1.6熱循環風扇................................................................... 114
5.2 軟體精進與開發......................................................................115
5.2.1 CopyCAD、PowerMILLL及Galil之Visual Basic開發模組安裝說明及巨集錄製方法.....................................117
5.2.2 電腦輔助生醫模型檔案切層.......................................121
5.2.3 雷射燒結路徑控制.......................................................127
5.2.4 讀檔控制模組...............................................................137
5.3 系統軟/硬體功能測試............................................................140
5.3.1 軟硬骨組織支架雷射燒快速成型系統開發之硬體測試...................................................................................141
5.3.2 軟硬骨組織支架雷射燒快速成型系統開發之軟體測試...................................................................................148
5.4 本章總結.................................................................................155
第六章 生醫材料特性測試及實體支架製作......................................156
6.1利用粒徑分析儀與光學顯微鏡分析六種不同生醫原材料及燒結製作完成支架之粒徑大小................................................157
6.2利用骨水泥(廠牌ZIMMER)燒結11種不同孔洞型式之雙層結構組織支架..........................................................................172
6.3製作不同孔隙率10%、20%、30%、40%等四種單層結構之組織支架..................................................................................177
6.4利用骨水泥(廠牌ZIMMER)測試本機台燒結製程參數(即雷射功率)對燒結完成支架品質之影響.................................182
6.5利用骨水泥(廠牌ZIMMER)進行材料預熱燒結測試.........182
6.6骨水泥與生醫材料(ZIMMER與HA)混合燒結測試..........184
6.7 利用股骨及半月板之生醫模型製作表面光滑內部具有孔洞及內外部具有孔洞之組織支架..............................................186
6.7.1 組織支架股骨實體製作................................................189
6.7.2 組織支架半月板實體製作............................................194
6.8 本章總結.................................................................................195
第七章 未來研究方向..........................................................................196
7.1組織支架最佳化單元結構軟體設計技術開發.......................196
7.2軟硬骨組織支架雷射燒結快速成型相關製作技術開發.......197
7.3生醫材料特性測試及組織支架實體製作...............................197
參考文獻................................................................................................198
附錄一 已投稿中文期刊抽印本
附錄二 擬投稿中文期刊抽印本
附錄三 擬投稿英文期刊抽印本
附錄四 Geomagic教學
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