臺灣博碩士論文加值系統

本研究目的在於開發含有醫療級硫酸鈣之可注射式聚電解質錯合體支架 (Injectable polyelectrolyte complex scaffold, IPS)，結合人類牙髓幹細胞 (Human dental pulp stem cell, hDPSC)於所設計之IPS，並以動物模型評估其於下顎骨組織再生能力。
　　在此醫療級硫酸鈣的合成中，利用硝酸鈣及硫酸鉀以濕式合成的方式生產各種類型的醫療級硫酸鈣，並藉由氯化鈣 (CaCl2)濃度與溫度的調控合成不同結晶類型的硫酸鈣水合物 (二水硫酸鈣 (CSD)、β-半水硫酸鈣 (β-CSH)、α-半水硫酸鈣 (α-CSH))。而由時間的測試結果得知，反應初期所析出的硫酸鈣水合物為CSD，隨著反應時間增加，生成物會轉化成β-CSH，最後再轉變成α-CSH。當反應溫度在80oC以下時，樣品大多為CSD；若將反應溫度控制在90oC時，硫酸鈣水合物的晶型會隨著氯化鈣濃度的增加而改變，其轉化路徑為: CSD → CSD + β-CSH → CSD + β-CSH + α-CSH → α-CSH。同時本研究更發現藉由反應時間及CaCl2濃度的變化，可以控制α-CSH的結晶尺寸，進而提升α-CSH水合後樣品的抗壓強度。由耦合電漿質譜儀及體內生物相容性測試證實，所生產的硫酸鈣水合物皆符合ASTM重金屬含量與生物相容性規範。實驗也成功建構硫酸鈣水合物的processing window，可做為後續生產不同硫酸鈣水合物之參數設定依據。
　　在IPS的設計中，乃利用靜態混鍊注射器來混合帶正電的幾丁聚醣 (Chitosan, CS)與帶負電的γ-聚麩胺酸 (γ-polyglutamic acid, γ-PGA) + 羧甲基纖維素納 (Carboxymethyl cellulose, CMC)，以形成的聚電解質錯合體來製作可注射式支架。實驗所設計的IPS固化時間小於1分鐘，凝膠率最高可達75%，並且具有連通多孔的構型，此結構在PBS中經過26週的降解實驗，依然具有相當良好的穩定性，且進一步證實具細胞相容性。
　　於米格魯犬齒槽骨缺損測試中發現，樣品植入後3週，IPS的新骨再生率為20.7%，而IPS/CSD則為50.1%，此結果皆比空白控制組高(0.5%, p < 0.05)；而植入後6週，IPS及IPS/CSD兩組的新骨再生率皆約為70%無統計上差異，但IPS/CSD組別的變異係數遠比IPS組來得低，亦即IPS/CSD, 在不同動物個體上所呈現的結果比較專一，骨組織再生性能的再現性比較高。以上結果得知，IPS中添加硫酸鈣，於植入骨缺損的初期能有效的促進骨組織的再生，並具有較高的實驗結果再現率。
　　本研究也藉由蘭嶼豬的下顎骨缺損模型來評估添加hDPSC於IPS/CSD對於骨組織再生之助益。由結果得知，空白控制組於術後8週的新骨再生率只有27%，與直接在缺損部位植入hDPSC的數值24.3%無統計上差異，IPS/CSD植入後兩個月其促進骨組織癒合的效果非常顯著，新骨再生率約為79%，而在加入hDPSC後提升至91.8%，顯示hDPSC能有效提升骨移植材對骨組織的修復能力。

The purpose of this study is to develop a injectable polyelectrolyte complex scaffold (IPS) containing medical grade calcium sulfate, human dental pulp stem cell (hDPSC) was also added in IPS system and estimated the performance by animal model.
In medical grade calcium sulfate synthesis, we want t synthesize various types of medical grade calcium sulfate by providing Ca+ and SO4- ions in CaCl2 solution at a suitable temperature. The calcium sulfate dihydrate (CSD) was found to be an intermediate phase that converts to CSH during the synthesis process, and α-CSH was gradually transformed from β-CSH over time. Moreover, the kinetic of CSD conversion to CSH was strongly accelerated by increasing the CaCl2 concentration. As the reaction temperature was fixed in 90oC, the form of the CS reactant with an increase in the CaCl2 concentration was in the following sequence: CSD → CSD + β-CSH → CSD + β-CSH + α-CSH → α-CSH. In this study, the synthesis processing window of the CS reactant was established according the test results, and it is worth noting that all phases of CS hydrate could be synthesized with this system and well predicted by the constructed processing window.
In development part of IPS, oppositely charged polyelectrolytes (chitosan/γ-polyglutamic acid) were mixed and injected using a static injection mixer. Ionic crosslinking of the IPS with a rapid gelling time (< 1 min), a high gel content (75%), and interconnected pore structures was achieved without using a toxic crosslinker. The IPS had satisfactory stability in PBS within 26 weeks. The MTT assay and SEM observations indicated that the IPS had satisfactory cell compatibility. In an animal study, IPS, IPS/calcium sulfate dihydrate (CSD), and CSD (granules) were implanted within canine alveolar defects. After 3 weeks, the IPS/CSD group had the highest new bone formation (50.1%) (p < 0.05). After 6 weeks, the new bone formation of the IPS/CSD group was 71.6% with the lowest coefficient of variation; this indicates that adding CSD to the IPS enhanced bone regeneration. The study also used the Lanyu pig jaw bone defect model to assess the benefit of adding hDPSC in IPS/CSD for the of bone regeneration. Postoperation 8 weeks, the new bone regeneration ratio of empty control was only about 27.0% that was no statistical difference with empty control with hDPSC (24.3%). In IPS/CSD group, promotion of bone healing effect is very remarkable, which new bone regeneration ratio is about 79%, moveover, adding hDPSC in IPS/CSD the new bone formation further increased to 91.8% that confirmed hDPSC can improve the performance of bone graft for bone repair.

謝誌………………………………………………………………………2摘要………………………………………………………………………3
Abstract………………………………………………………………….5
目錄………………………………………………………………………7
表目錄………………………………………………………………......14
圖目錄…………………………………………………………………..15
第一章 前言……………………………………………………………17
1.1 研究動機及重要性……………………………………………...17
1.2 研究目的………………………………………………………...23
1.3 研究假說………………………………………………………...24
第二章 文獻回顧………………………………………………………26
2.1 骨組織概論……………………………………………………...26
2.1.1 骨組織之組成結構與特性…………………………………26
2.1.2 骨組織的更新與重塑………………………………………28
2.1.3骨缺損之類型與臨床治療策略……………………………..28
2.2骨組織工程……………………………………………………….31
2.2.1 生長因子於骨組織工程……………………………………31
2.2.2 幹細胞於骨組織工程……………………………………....32
2.2.3 支架於骨組織工程……………………………..…………..35
2.3 骨缺損於臨床之治療方式……………………………………...37
2.3.1自體或異體骨移植材之使用………………………………..38
2.3.2合成骨移植材之使用………………………………………..38
2.3.2.1連通多孔塊狀骨移植材………………………………...41
2.3.2.2 顆粒及泥狀骨移植材……………………………….....43
2.3.3 具有抑菌功能之骨移植材…………………………………44
2.4 可注射式基材之設計與發展…………………………………...46
2.4.1. 化學交聯劑與化學修飾交聯法…………………………...46
2.4.2. 離子交聯法………………………………………………...47
2.4.3. 聚電解質錯合體…………………………………………...48
2.4.3.1 聚電解質錯合體於生醫工程之發展………………...48
2.4.3.2 幾丁聚醣之特性及於聚電解質複合體之應用……...50
2.4.3.3 γ-聚麩胺酸之特性及於聚電解質複合體之應用…..51
2.5醫療用硫酸鈣之概論…………………………………………...54
2.5.1 硫酸鈣的類型以及醫療級硫酸鈣應用…………………..54
2.5.2醫療級硫酸鈣摻混於生醫材料之應用……………………55
2.5.3醫療級硫酸鈣之結晶與相轉變行為………………………56
2.5.4 半水硫酸鈣的傳統合成法………………………………..57
2.5.5 利用濕式沉澱法於電解質液體中合成硫酸鈣水合物…..58
2.6 人類牙髓幹細胞於骨組織工程上之發展…………………….60
2.6.1人類牙髓幹細胞之低免疫排斥性特性…………………....61
2.6.2 人類牙髓幹細胞於骨再生之研究………………………..62
第三章 材料與方法……………………………………………………67
3.1 實驗材料與儀器設備…………………………………………...67
3.1.1 實驗材料……………………………………………………67
3.1.2 實驗設備……………………………………………………68
3.2 實驗流程………………………………………………………...70
3.3 醫療級硫酸鈣水合物實驗方法………………………………...71
3.3.1 醫療級硫酸鈣水合物合成…………………………………71
3.3.2 醫療級硫酸鈣水合物之鑑定與分析………………………72
3.3.2.1 廣角X光繞射儀……………………………………….66
3.3.2.2 熱示差掃瞄卡量計…………………………………….67
3.3.2.3 掃描式電子顯微鏡…………………………………….68
3.3.2.5 結晶大小與長寬比量測……………………………….69
3.3.2.6 抗壓強度測試………………………………………….70
3.3.2.7 重金屬含量分析……………………………………….70
3.4 可注射聚電解質錯合體之製備與分析………………………...72
3.4.1 可注射聚電解質錯合體支架製備…………………………77
3.4.2 可注射聚電解質錯合體支架之物化性分析………………77
3.4.2.1 凝膠時間量測………………………………………….77
3.4.2.2 凝膠率分析…………………………………………….78
3.4.2.3 平衡膨潤度量測……………………………………….78
3.4.2.4 傅立葉轉換紅外線光譜儀分析……………………….79
3.4.2.5 ISO10993-9體外降解測試…………………………….79
3.4.2.6 類骨母細胞(MC3T3E1)培養技術 ………..…..……..80
3.4.2.7 人類牙髓幹細胞之萃取培養技術…………………….84
3.4.2.8 ISO10993-5細胞相容性測試………………………….85
3.4.2.9 類骨母細胞貼附性測試………………………..……...86
3.5可塑形之抑菌聚電解質錯合體支架的製備與分析…………….88
3.5.1可塑形之抑菌聚電解質錯合體支架製備…………………..88
3.5.2 可塑形之抑菌聚電解質錯合體的物化性分析……………88
3.5.2.1 凝膠率分析…………………………………………….88
3.5.2.2 平衡膨潤度量測……………………………………….89
3.5.2.3 體積改變率…………………………………………….89
3.5.2.4 抑菌測試……………………………………………….89
3.5.2.5 ISO10993-5細胞相容性測試………………………….90
3.5.2.6 類骨母細胞貼附性測試……………………………….90
3.6動物實驗………………………………………………………….91
3.6.1 體內生物相容性評估……………………………………….91
3.6.2 骨移植材促進骨組織再生之體內酵力評估……………….92
3.6.2.1米格魯下顎齒槽骨缺損模型建立及樣品植入手術…....92
3.6.2.2 蘭嶼豬下顎骨缺損模型建立及樣品植入手術………..93
3.7 組織學評估……………………………………………………...98
3.7.1 骨組織取樣及石蠟樣品切片製作方式……………………98
3.7.2 骨組織之蘇木紫與伊紅染色法…………………………..100
3.7.3 計算新骨再生率…………………………………………..100
3.8 統計方法……………………………………………………….102
3.8.1 變異係數分析……………………………………………..102
3.8.2 單因子變異數分析………………………………………..102
第四章 合成醫療級硫酸鈣水合物之結果……………............……..103
4.1 硫酸鈣水合物之合成與鑑定………………………………….103
4.1.1 反應時間對於硫酸鈣水合物結晶類型的影響…………..104
4.1.2 反應溫度對於硫酸鈣水合物結晶類型的影響…………..105
4.1.3 氯化鈣濃度對於硫酸鈣水合物結晶類型的影響………..105
4.1.4 建構水熱法合成硫酸鈣水合物之processing window.....106
4.1.5 反應條件對於α-CSH結晶大小與長寬比量之影響…….107
4.1.6 結晶型態對於α-CSH水合後抗壓強度之影響…………108
第五章 聚電解質錯合體支架之結果……………………............…..109
5.1 可注射聚電解質錯合體支架之體外物化性測試…………….110
5.1.1 混合方式及靜態混鍊器葉片數量對於可注射聚電解質錯合體結構形成之影響………………………………………..109
5.1.2 配方對於凝膠時間之影響………………………………..110
5.1.3 配方對於凝膠率及平衡膨潤度之影響…………………..111
5.1.4 可注射聚電解質錯合體支架的傅立葉轉換紅外線光譜..112
5.1.5 可注射聚電解質錯合體支架之結構觀察………………..113
5.1.6 可注射聚電解質錯合體支架之體外降解行為觀察……..114
5.1.7 可注射聚電解質錯合體支架之細胞相容性評估及類骨母細胞於可注射聚電解質錯合體支架之貼附狀態…………..114
5.2 可塑形之抑菌電解質錯合體支架的體外物化性測試……….116
5.2.1可塑形之抑菌電解質錯合體的製作………………………116
5.2.2 配方對於成膠性質之影響………………………………..117
5.2.3 不同凝膠率樣品於傅立葉轉換紅外線光譜上之差異…..118
5.2.4 可塑形之抑菌電解質錯合體支架的結構觀察…………..118
5.2.5 可塑形之抑菌電解質錯合體支架之抑菌性……………..119
5.2.6可塑形之抑菌電解質錯合體支架的細胞培養測試……..120
第六章 動物實驗……………………………………………………..121
6.1 硫酸鈣樣品的體內生物相容性評估………………….……121
6.2 可塑形之抑菌電解質錯合體支架的體內生物相容性評估.121
6.3 硫酸鈣的添加對可注射聚電解質錯合體支架於米格魯犬齒槽骨缺損再生之效益……………………………………….122
6.4 評估人類牙髓幹細胞的添加對於可注射聚電解質錯合體支架於蘭嶼豬下顎骨缺損再生之效益……………………….123
第七章 討論…………………………………………………………..126
7.1 反應條件對於醫療級硫酸鈣水合物結晶類型的影響.........126
7.2 可注射聚電解質錯合體支架之體外物化性.........................129
7.3 可塑型之抑菌聚電解質錯合體支架.....................................131
7.4 利用動物模型對植入樣品進行生物相容性及骨再生效益之觀察........................................................................................134
第八章 結論…………………………………………………………..139
參考文獻………………………………………………………………143
論文及專利發表………………………………………………………188
 
表目錄
表4-1 溼式硫酸鈣合成法所有條件及硫酸鈣產物的晶型統整表…156
表4-2硫酸鈣水合物之重金屬含量測試……………,………………157
表4-3不同反應參數對於α-CSH晶型尺寸之影響及其抗壓強度之差異(反應溫度90oC) ……….................…………..……………158
表5-1不同γ-PGA 含量之PEC樣品對於樣品凝膠性質之影響......159
表5-2不同γ-PGA 含量之PEC樣品對於抑菌圈大小之影響..........160
表6-1 IPS樣品於狗下顎齒槽骨缺損模型中之新骨再生率平均值..161
表6-2 利用蘭嶼豬下顎骨缺損模型評估hDPSC於骨移植材的添加對新骨再生率之影響……………………………………………162
 
圖目錄
圖4-1. 本研究之溼式硫酸鈣合成法流程圖………………………...162
圖4-2. 反應時間對於硫酸鈣水合物晶型之影響…………………...163
圖4-3. SEM照片x1000(A)β-半水硫酸鈣(CSH)、(B)α-CSH..….....164
圖 4-4. 反應溫度對於硫酸鈣水合物晶型之影響…………………..165
圖 4-5. 氯化鈣濃度對於硫酸鈣水合物晶型之影響………………..166
圖4-6. 掃描式電子顯微鏡照片(A)二水硫酸鈣(CSD)+β-半水硫酸鈣 (β-CSH)+α-CSH、(B)β-CSH+α-CSH……………………….167
圖4-7. 濕式硫酸鈣合成法的Processing window…………………..168
圖4-8. 將反應時間增加至18 h所合成的α-CSH之電子掃描式電子顯微鏡照片(CaCl2濃度3.5M、反應溫度90oC)……………......169
圖5-1-1. 本實驗所使用的靜態混鍊注射器及其混合原理…………170
圖5-1-2. 靜態混鍊器葉片數量及混合方式對於可注射聚電解質錯合體結構形成之影響…………………………………………171
圖5-1-3. 不同聚電解質濃度對於凝膠時間的影響……….......…….172
圖5-1-4. 不同聚電解質濃度對於凝膠率及平衡膨潤度的影響，凝膠率(Gel content, GC) (■)、(◆) 平衡膨潤度(Equilibrium swelling, ES, at 25 ?aC in PBS for 24 h)…...........…………173
圖5-1-5. IPS的FTIR光譜……………….…………………………..174
圖5-1-6. (A)IPS注射於模具固化後之型態、(B)IPS之剖面電SEM照片、(C) IPS的表面微結構圖………………………………175
圖5-1-7. IPS於PBS環境中的降解曲線……………………………..176
圖5-1-8. IPS的細胞測試結果………………………………………..177
圖5-2-1. 混合方式對於可塑型抑菌之聚電解質錯合體支架的成膠性質影響……………………………………………………....178
圖5-2-2. 已成型的抑菌可塑型之聚電解質錯合體支架……………179
圖5-2-3. 抑菌可塑型之聚電解質錯合體支架的FTIR光譜….……180
圖5-2-4. 抑菌可塑型之聚電解質錯合體支架之剖面SEM圖……..181
圖5-2-5. 抑菌可塑型之聚電解質錯合體支架的細胞相容性測試....182
圖5-2-6. MC3T3E1 cells於抑菌可塑型之聚電解質錯合體支架上生長狀況的SEM照片…………………………………………..183
圖6-1. 硫酸鈣植入犬隻拔牙傷口後十週之H&E染色組織學觀察.184
圖6-2. 抑菌可塑型之聚電解質錯合體支架樣品植入犬隻拔牙傷口後十週的H&E染色組織學觀察………………………………185
圖6-3. IPS樣品植入犬隻齒槽骨缺損後之H&E染色組織學觀察...186
圖6-4. IPS樣品及含人類牙髓幹細胞之IPS植入豬隻下顎骨缺損八週後之H&E染色組織學觀察…………………………………..187

[1] Taylor GI. The Current Status of Free Vascularized Bone Grafts. Clinics in Plastic Surgery 1983;10:185-209.
[2] U.S and Western European Bone Graft Substitute Market. Nelesh Patel; 2006.
[3] Irinakis T, Tabesh M. Preserving the Socket Dimensions with Bone Grafting in Single Sites: an Esthetic Surgical Approach When Planning Delayed Implant Placement. The Journal of Oral Implantology. 2007;33:156-63.
[4] Palti A, Hoch T. A Concept for the Treatment of Various Dental Bone Defects. Implant Dentistry. 2002;11:73-8.
[5] The Global Market for Orthobiologic Products. Espicom Business Intelligence; 2010.
[6] Xu HH, Weir MD, Burguera EF, Fraser AM. Injectable and Macroporous Calcium Phosphate Cement Scaffold. Biomaterials. 2006;27:4279-87.
[7] Ito K, Yamada Y, Nagasaka T, Baba S, Ueda M. Osteogenic Potential of Injectable Tissue-Engineered Bone: a Comparison Among Autogenous Bone, Bone Substitute (Bio-oss), Platelet-Rich Plasma, and Tissue-Engineered Bone with Respect to Their Mechanical Properties and Histological Findings. Journal of Biomedical Materials Research-Part A. 2005;73:63-72.
[8] Yao CH, Liu BS, Hsu SH, Chen YS. Calvarial Bone Response to a Tricalcium Phosphate-Genipin Crosslinked Gelatin Composite. Biomaterials. 2005;26:3065-74.
[9] Valle SD, Miño N, Muñoz F, González A, Planell JA, Ginebra MP. In Vivo Evaluation of an Injectable Macroporous Calcium Phosphate Cement. Journal of Materials Science: Materials in Medicine. 2007;18:353-61.
[10] Xu HHK, Takagi S, Quinn JB, Chow LC. Fast-Setting Calcium Phosphate Scaffolds with Tailored Macropore Formation Rates for Bone Regeneration. Journal of Biomedical Materials Research-Part A. 2004;68:725-34.
[11] Apelt D, Theiss F, El-Warrak AO, Zlinszky K, Bettschart-Wolfisberger R, Bohner M, et al. In Vivo Behavior of Three Different Injectable Hydraulic Calcium Phosphate Cements. Biomaterials. 2004;25:1439-51.
[12] Yu L, Ding J. Injectable Hydrogels as Unique Biomedical Materials. Chemical Society Reviews. 2008;37:1473-81.
[13] Hou QP, De Bank PA, Shakesheff KM. Injectable Scaffolds for Tissue Regeneration. Journal of Materials Chemistry. 2004;14:1915-23.
[14] Kretlow JD, Klouda L, Mikos AG. Injectable Matrices and Scaffolds for Drug Delivery in Tissue Engineering. Advanced Drug Delivery Reviews 2007;59:263-73.
[15] Jabbari E, Wang S, Lu L, Gruetzmacher JA, Ameenuddin S, Hefferan TE, et al. Synthesis, Material Properties, and Biocompatibility of a Novel Self-Cross-Linkable Poly(Caprolactone Fumarate) as an Injectable Tissue Engineering Scaffold. Biomacromolecules. 2005;6:2503-11.
[16] Balakrishnan B, Jayakrishnan A. Self-Cross-Linking Biopolymers as Injectable in Situ Forming Biodegradable Scaffolds. Biomaterials. 2005;26:3941-51.
[17] Li Q, Wang J, Shahani S, Sun DD, Sharma B, Elisseeff JH, et al. Biodegradable and Photocrosslinkable Polyphosphoester Hydrogel. Biomaterials. 2006;27:1027-34.
[18] Thomas MV, Puleo DA. Calcium Sulfate: Properties and Clinical Applications. Journal of Biomedical Materials Research-Part B Applied Biomaterials. 2009;88:597-610.
[19] Al Ruhaimi KA. Effect of Adding Resorbable Calcium Sulfate to Grafting Materials on Early Bone Regeneration in Osseous Defects in Rabbits. International Journal of Oral and Maxillofacial Implants. 2000;15:859-64.
[20] Schemitsch EH, Togawa D, Reid J, Bauer TW, Sakai H, Hawkins M, et al. Evaluation of the Use of Calcium Sulfate HA/TCP Composite in a Canine Metaphyseal Defect Model. Journal of Bone and Joint Surgery. 2008;90-B:66.
[21] Lazáry Á, Balla B, Kósa JP, Bácsi K, Nagy Z, Takács I, et al. Effect of Gypsum on Proliferation and Differentiation of MC3T3-E1 Mouse Osteoblastic Cells. Biomaterials. 2007;28:393-9.
[22] Yamaguchi T, Chattopadhyay N, Kifor O, Butters Jr RR, Sugimoto T, Brown EM. Mouse Osteoblastic Cell Line (MC3T3-E1) Expresses Extracellular Calcium (Ca2+(o))-Sensing Receptor And its Agonists Stimulate Chemotaxis and Proliferation of MC3T3-E1 Cells. Journal of Bone and Mineral Research. 1998;13:1530-8.
[23] Eichler J, Hutzschenreuter P, Rosenbladt I. The Behavior of Biological Parameters in Experimental Hyperthermia. Anaesthesist. 1969;18:210-5.
[24] Brown KLB, Cruess RL. Bone and Cartilage Transplantation in Orthopaedic Surgery. A review. Journal of Bone and Joint Surgery - Series A. 1982;64:270-9.
[25] Gross TP, Cox QGN, Jinnah RH. History and Current Application of Bone Transplantation. Orthopedics. 1993;16:895-900.
[26] Hardouin P, Anselme K, Flautre B, Bianchi F, Bascoulenguet G, Bouxin B. Tissue Engineering and Skeletal Diseases. Joint Bone Spine. 2000;67:419-24.
[27] Mistry AS, Mikos AG. Tissue Engineering Strategies for Bone Regeneration. 2005. p. 1-22.
[28] Mundy GR, Boyce B, Hughes D, Wright K, Bonewald L, Dallas S, et al. The Effects of Cytokines and Growth Factors on Osteoblastic Cells. Bone. 1995;17:71S-5S.
[29] Hamm AW. A Histological Study of the Early Phase of Bone Repair. Journal of Bone and Joint Surgery. 1930;12:827-44.
[30] Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M. Formation of Bone and Cartilage by Marrow Stromal Cells in Diffusion Chambers in Vivo. Clinical Orthopaedics and Related Research. 1980:294-307.
[31] Long MW. Osteogenesis and Bone-Marrow-Derived Cells. Blood Cells, Molecules, and Diseases. 2001;27:677-90.
[32] Harris CT, Cooper LF. Comparison of Bone Graft Matrices for Human Mesenchymal Stem Cell-Directed Osteogenesis. Journal of Biomedical Materials Research - Part A. 2004;68:747-55.
[33] Mistry AS, Mikos AG. Tissue Engineering Strategies for Bone Regeneration. Advances in Biochemical Engineering. 2005;94:1-22.
[34] Roskelley CD, Srebrow A, Bissell MJ. A Hierarchy of ECM-Mediated Signalling Regulates Tissue-Specific Gene Expression. Current Opinion in Cell Biology. 1995;7:736-47.
[35] Bissell MJ, Hall HG, Parry G. How Does the Extracellular Matrix Direct Gene Expression? Journal of Theoretical Biology. 1982;99:31-68.
[36] Boudreau N, Myers C, Bissell MJ. From Laminin to Lamin: Regulation of Tissue-Specific Gene Expression by the ECM. Trends in Cell Biology. 1995;5:1-4.
[37] Bhumiratana S, Grayson WL, Castaneda A, Rockwood DN, Gil ES, Kaplan DL, et al. Nucleation and Growth of Mineralized Bone Matrix on Silk-Hydroxyapatite Composite Scaffolds. Biomaterials. 2011;32:2812-20.
[38] Thimm BW, Wüst S, Hofmann S, Hagenmüller H, Müller R. Initial Cell Pre-Cultivation can Maximize ECM Mineralization by Human Mesenchymal Stem Cells on Silk Fibroin Scaffolds. Acta Biomaterialia. In press.
[39] Ebraheim NA, Elgafy H, Xu R. Bone-Graft Harvesting from Iliac and Fibular Donor Sites: Techniques and Complications. The Journal of the American Academy of Orthopaedic Surgeons. 2001;9:210-8.
[40] Coventry MB, Tapper EM. Pelvic Instability: a Consequence of Removing Iliac Bone for Grafting. Journal Bone Joint Surgery American. 1972;54:83-101.
[41] Garg A. Bone biology, Harvesting, Drafting for Dental Implant; Rationale and Clinical Applications. Chicago: Quintessence; 2004.
[42] Alexander R, Christine K, Simon Z, Gerd W. Synchrotron-Tomography for Evaluation of Bone Tissue Regeneration using rapidly Resorbable Bone Substitute Materials. Euro NDT Conference; 2006:1-9.
[43] Knabe C, Houshmand A, Berger G, Ducheyne P, Gildenhaar R, Kranz I, et al. Effect of Rapidly Resorbable Bone Substitute Materials on the Temporal Expression of the Osteoblastic Phenotype in Vitro. Journal Biomedical Material Research Part-A. 2008;84:856-68.
[44] Branemark PI. Osseointegration and Its Experimental Background. The Journal of Prosthetic Dentistry. 1983;50:399-410.
[45] Whang K, Healy KE, Elenz DR, Nam EK, Tsai DC, Thomas CH, et al. Engineering Bone Regeneration with Bioabsorbable Scaffolds with Novel Microarchitecture. Tissue Engineering; 1999;5:35-51.
[46] Yoshikawa H, Tamai N, Murase T, Myoui A. Interconnected Porous Hydroxyapatite Ceramics for Bone Tissue Engineering. Journal of the Royal Society Interface. 2009;6 Suppl 3:S341-8.
[47] Fujibayashi S, Neo M, Kim HM, Kokubo T, Nakamura T. Osteoinduction of Porous Bioactive Titanium Metal. Biomaterials. 2004;25:443-50.
[48] Xu HHK, Burguera EF, Carey LE. Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures. Biomaterials. 2007;28:3786-96.
[49] Dirschl DR, Almekinders LC. Osteomyelitis. Common Causes and Treatment Recommendations. Drugs. 1993;45:29-43.
[50] Lew DP, Waldvogel FA. Current concepts: Osteomyelitis. New England Journal of Medicine. 1997;336:999-1007.
[51] Kapusnik JE, Parenti F, Sande MA. The Use of Rifampicin in Staphylococcal Infections. A review. Journal of Antimicrobial Chemotherapy. 1984;13:61-6.
[52] Verne E, Di Nunzio S, Bosetti M, Appendino P, Vitale Brovarone C, Maina G, et al. Surface Characterization of Silver-Doped Bioactive Glass. Biomaterials. 2005;26:5111-9.
[53] Kawashita M, Tsuneyama S, Miyaji F, Kokubo T, Kozuka H, Yamamoto K. Antibacterial Silver-Containing Silica Glass Prepared by Sol-Gel Method. Biomaterials. 2000;21:393-8.
[54] Vik H, Andersen KJ, Julshamn K, Todnem K. Neuropathy Caused by Silver Absorption from Arthroplastry Cement. Lancet. 1985;325:872-.
[55] Alt V, Bechert T, Steinrücke P, Wagener M, Seidel P, Dingeldein E, et al. An In Vitro Assessment of the Antibacterial Properties and Cytotoxicity of Nanoparticulate Silver Bone Cement. Biomaterials. 2004;25:4383-91.
[56] Kim IY, Seo SJ, Moon HS, Yoo MK, Park IY, Kim BC, et al. Chitosan and Its Derivatives for Tissue Engineering Applications. Biotechnology Advances. 2008;26:1-21.
[57] Lee KY, Alsberg E, Mooney DJ. Degradable and Injectable Poly(Aldehyde Guluronate) Hydrogels for Bone Tissue Engineering. Journal of Biomedical Materials Research. 2001;56:228-33.
[58] Kuo CK, Ma PX. Ionically Crosslinked Alginate Hydrogels as Scaffolds for Tissue Engineering: Part 1. Structure, Gelation Rate and Mechanical Properties. Biomaterials. 2001;22:511-21.
[59] Luginbuehl V, Wenk E, Koch A, Gander B, Merkle HP, Meinel L. Insulin-Like Growth Factor I-Releasing Alginate-Tricalciumphosphate Composites for Bone Regeneration. Pharmaceutical Research. 2005;22:940-50.
[60] Shoichet MS, Li RH, White ML, Winn SR. Stability of Hydrogels Used in Cell Encapsulation: An In Vitro Comparison of Alginate and Agarose. Biotechnol Bioeng. 1996;50:374-81.
[61] Rowley JA, Madlambayan G, Mooney DJ. Alginate Hydrogels as Synthetic Extracellular Matrix Materials. Biomaterials. 1999;20:45-53.
[62] Li QL, Chen ZQ, Darvell BW, Liu LK, Jiang HB, Zen Q, et al. Chitosan-Phosphorylated Chitosan Polyelectrolyte Complex Hydrogel as an Osteoblast Carrier. Journal Biomedical Material Reseacher Part-B Applied Biomater. 2007;82:481-6.
[63] Dragan S, Cristea M, Luca C, Simionescu BC. Polyelectrolyte complexes. I. Synthesis and Characterization of Some Insoluble Polyanion-Polycation Complexes. Journal of Polymer Science, Part A: Polymer Chemistry. 1996;34:3485-94.
[64] Arndt KF, Morgenstern B, Röder T. Light Scattering Studies on Polyelectrolyte Complexes. Macromolecular Symposia. 2000;162:1-21.
[65] Hartig SM, Greene RR, Dikov MM, Prokop A, Davidson JM. Multifunctional nanoparticulate polyelectrolyte complexes. Pharmaceutical Research. 2007;24:2353-69.
[66] Wang C, Zhan R, Pu KY, Liu B. Cationic Polyelectrolyte Amplified Bead Array for DNA Detection with Zeptomole Sensitivity and Single Nucleotide Polymorphism Selectivity. Advanced Functional Materials. 2010;20:2597-604.
[67] Lin YS, Renbutsu E, Morimoto M, Okamura Y, Tsuka T, Saimoto H, et al. Preparation of Stable Chitosan-Carboxymethyl Dextran Nanoparticles. Journal of Nanoscience and Nanotechnology. 2009;9:2558-65.
[68] Elzatahry AA, Eldin MSM, Soliman EA, Hassan EA. Evaluation of Alginate-Chitosan Bioadhesive Beads as a Drug Delivery System for the Controlled Release of Theophylline. Journal of Applied Polymer Science. 2009;111:2452-9.
[69] Zhao Q, Qian J, An Q, Sun Z. Layer-By-Layer Self-Assembly of Polyelectrolyte Complexes and Their Multilayer Films for Pervaporation Dehydration of Isopropanol. Journal of Membrane Science. 2009;346:335-43.
[70] Tsai GJ, Su WH. Antibacterial Activity of Shrimp Chitosan Against Escherichia coli. Journal of Food Protection. 1999;62:239-43.
[71] Jiang L, Li Y, Zhang L, Wang X. Preparation and Characterization of a Novel Composite Containing Carboxymethyl Cellulose Used for Bone Repair. Materials Science and Engineering C. 2009;29:193-8.
[72] Coimbra P, Ferreira P, de Sousa HC, Batista P, Rodrigues MA, Correia IJ, et al. Preparation and Chemical and Biological Characterization of a Pectin/Chitosan Polyelectrolyte Complex Scaffold for Possible Bone Tissue Engineering Applications. International Journal of Biological Macromolecules. 2011;48:112-8.
[73] Hand RJ. Calcium Sulfate Hydrates: a Review. Brit Ceram T. 1997;96:116-20.
[74] Randolph DA, Negri JL, Devine TR, Gitelis S. Controlled Dissolution Pellet Containing Calcium Sulfate. United States Patent 5614206, 1997.
[75] Y. Ling, Demopoulos GP. Preparation of α-Calcium Sulfate Hemihydrate by Reaction of Sulfuric Acid with Lime. Industrial & Engineering Chemistry Research. 2005;44:715-24.
[76] Murashima Y, Yoshikawa G, Wadachi R, Sawada N, Suda H. Calcium Sulphate as a Bone Substitute for Various Osseous Defects in Conjunction with Apicectomy. International Endodontic Journal. 2002;35:768-74.
[77] Cho BC, Park JW, Baik BS, Kim IS. Clinical Application of Injectable Calcium Sulfate on Early Bony Consolidation in Distraction Osteogenesis for the Treatment of Craniofacial Microsomia. Journal of Craniofacial Surgery. 2002;13:465-75.
[78] Benoit MA, Mousset B, Delloye C, Bouillet R, Gillard J. Antibiotic-Loaded Plaster of Paris Implants Coated with Poly Lactide-co-Glycolide as a Controlled Release Delivery System for the Treatment of Bone Infections. International Orthopaedics. 1997;21:403-8.
[79] Rosenblum SF, Frenkel S, Ricci JR, Alexander H. Diffusion of Fibroblast Growth Factor from a Plaster of Paris Carrier. Journal of Biomaterials Applications. 1993;4:67-72.
[80] McConville JT, Ross AC, Florence AJ, Stevens HNE. Erosion Characteristics of an Erodible Tablet Incorporated in a Time-Delayed Capsule Device. Drug Development and Industrial Pharmacy. 2005;31:79-89.
[81] Nilsson M, Wang JS, Wielanek L, Tanner KE, Lidgren L. Biodegradation and Biocompatability of a Calcium Sulphate-Hydroxyapatite Bone Substitute. Journal of Bone and Joint Surgery-Series B. 2004;86:120-5.
[82] Urban RM, Turner TM, Hall DJ, Inoue N, Gitelis S. Increased Bone Formation Using Calcium Sulfate-Calcium Phosphate Composite Graft. Clinical Orthopaedics and Related Research. 2007:110-7.
[83] Wiedeman HG, Rössler M. Thermo-Optical and Thermo-Analytical Investigations of Gypsum (Calcium Sulfate-Water). Thermochimica Acta. 1985;95:145-53.
[84] Bobrov BS, Romashkov AV, Andreeva EP. Mechanism of Formation and Growth of alpha-Semihydrate Gypsum Crystals. Neorganiceskie Materialy. 1987;23:497-500.
[85] Meij R, Vredenbregt LHJ, Te Winkel H. The Fate and Behavior of Mercury in Coal-Fired Power Plants. Journal of the Air & Waste Management Association . 2002;52:912-7.
[86] Kappe J. Utilization of Residuals from Flue Gas Desulfurization. Environmental Progress. 1986;5:191-6.
[87] Lewry AJ, Williamson J. The Setting of Gypsum Plaster-Part I The Hydration of Calcium Sulphate Hemihydrate. Journal of Materials Science. 1994;29:5279-84.
[88] Zurz A. IO, F. Thiemann and K.Berghofer. Autoclave-Free Formation of α-Hemihydrate Gypsum. Journal of the American Ceramic Society. 1991;74:1117-24.
[89] Freyer D, Voigt W. Crystallization and Phase Stability of CaSO4 and CaSO4-Based Salts. Monatsh Chem. 2003;134:693-719.
[90] P. Wang, E. J. Lee, C. S. Park, B. H. Yoon, D. S. Shin, H. E. Kim. Calcium Sulfate Hemihydrate Powders with a Controlled Morphology for Use as Bone Cement. Journal of the American Ceramic Society. . 2008;91:2039-42.
[91] Liu H, Gronthos S, Shi S. Dental Pulp Stem Cells. Methods in Enzymology. 2006. 99-113.
[92] Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S. The Efficacy of Mesenchymal Stem Cells to Regenerate and Repair Dental Structures. Orthodontics & craniofacial research. 2005;8:191-9.
[93] Arthur A, Rychkov G, Shi S, Koblar SA, Gronthose S. Adult Human Dental Pulp Stem Cells Differentiate Toward Functionally Active Neurons Under Appropriate Environmental Cues. Stem Cells. 2008;26:1787-95.
[94] Gandia C, Armian ANA, Garca-Verdugo JM, Lled E, Ruiz A, Miana MD, et al. Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction. Stem Cells. 2008;26:638-45.
[95] Pierdomenico L, Bonsi L, Calvitti M, Rondelli D, Arpinati M, Chirumbolo G, et al. Multipotent Mesenchymal Stem Cells with Immunosuppressive Activity can be Easily Isolated from Dental Pulp. Transplantation. 2005;80:836-42.
[96] Király M, Kádár K, Horváthy DB, Nardai P, Rácz GZ, Lacza Z, et al. Integration of Neuronally Predifferentiated Human Dental Pulp Stem Cells into Rat Brain in vivo. Neurochemistry International. In press.
[97] d''Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A, et al. Human Postnatal Dental Pulp Cells Co-differentiate into Osteoblasts and Endotheliocytes: A Pivotal Synergy Leading to Adult Bone Tissue Formation. Cell Death and Differentiation. 2007;14:1162-71.
[98] Riccio M, Resca E, Maraldi T, Pisciotta A, Ferrari A, Bruzzesi G, et al. Human Dental Pulp Stem Cells Produce Mineralized Matrix in 2D and 3D Cultures. European Journal of Histochemistry. 2010;54:205-13.
[99] De Mendonca Costa A, Bueno DF, Martins MT, Kerkis I, Kerkis A, Fanganiello RD, et al. Reconstruction of Large Cranial Defects in Nonimmunosuppressed Experimental Design with Human Dental Pulp Stem Cells. Journal of Craniofacial Surgery. 2008;19:204-10.
[100] D''Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, et al. Human Mandible Bone Defect Repair by the Grafting of Dental Pulp Stem/Progenitor Cells and Collagen Sponge Biocomplexes. European Cells and Materials. 2009;18:75-83.
[101] Chiang PC. Influence of Magnetic Cryopreservation on the Dental Pulp Stem cells. 2010.
[102] Brown C. Method of Producing Calcium Sulfate Alpha Hemihydrate 20020164281. United States Patent, 2003.
[103] Li Z, Ramay HR, Hauch KD, Xiao D, Zhang M. Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials. 2005;26:3919-28.
[104] Citeau A, Guicheux J, Vinatier C, Layrolle P, Nguyen TP, Pilet P, et al. In Vitro Biological Effects of Titanium Rough Surface Obtained by Calcium Phosphate Grid Blasting. Biomaterials. 2005;26:157-65.
[105] Dai Z, Yin J, Yan S, Cao T, Ma J, Chen X. Polyelectrolyte Complexes Based on Chitosan and Poly (L-Glutamic Acid). Polymer International. 2007;56:1122-7.
[106] Lin YH, Chung CK, Chen CT, Liang HF, Chen SC, Sung HW. Preparation of Nanoparticles Composed of Chitosan/Poly-Gamma-Glutamic Acid and Evaluation of Their Permeability Through Caco-2 cells. Biomacromolecules. 2005;6:1104-12.
[107] Peter M, Binulal NS, Nair SV, Selvamurugan N, Tamura H, Jayakumar R. Novel Biodegradable Chitosan-Gelatin/Nano-Bioactive Glass Ceramic Composite Scaffolds for Alveolar Bone Tissue Engineering. Chemical Engineering Journal. 2010;158:353-61.
[108] Karageorgiou V, Kaplan D. Porosity of 3D Biomaterial Scaffolds and Osteogenesis. Biomaterials. 2005;26:5474-91.
[109] Cho SH, Na YE, Ahn YJ. Growth-Inhibiting Effects of Seco-Tanapartholides Identified in Artemisia Princeps Var. Orientalis Whole Plant on Human Intestinal Bacteria. Journal of Applied Microbiology. . 2003;95:7-12.
[110] Tischler M, Misch CE. Extraction Site Bone Grafting in General Dentistry: Review of Applications and Principles. Dentistry Today. 2004;23:108+10-13.
[111] Bobrov BS, Romashkov AV, Andreeva EP. Mechanism of Formation and Growth of Alpha-Hemihydrate Gypsum Crystals. Inorganic Materials 1987;23:437-9.
[112] Guan B, Yang L, Wu Z, Shen Z, Ma X, Ye Q. Preparation of α-Calcium Sulfate Hemihydrate from FGD Gypsum in K, Mg-Containing Concentrated CaCl2 Solution under Mild Conditions. Fuel. 2009;88:1286-93.
[113] Z. Li, Demopoulos GP. Model-Based Construction of Calcium Sulfate Phase-Transition Diagrams in the HCl-CaCl2-H2O System Between 0 and 100 oC. Industrial & Engineering Chemistry Research. 2006;45:4517-24.
[114] Partridge EP, White AH. The Solubility of Calcium Sulfate from 0 to 200°. Journal of the American Chemical Society. 1929;51:360-70.
[115] Dahlgren SE. Calcium Sulfate Transitions in Superphosphate. Journal of Agricultural and Food Chemistry. 1960;8:411-2.
[116] Guan B, Ma X, Wu Z, Yang L, Shen Z. Crystallization Routes and Metastability of α-Calcium Sulfate Hemihydrate in Potassium Chloride Solutions Under Atmospheric Pressure. Journal of Chemical & Engineering Data. 2009;54:719-25.
[117] J. A. Dirksen, T. A. Ring. Fundamentals of Crystallization: Kinetic Effects on Particle Size Distributions and Morphology. Chemical Engineering Science.. 1991;46:2389-427.
[118] Hamdona SK, Al Hadad UA. Crystallization of Calcium Sulfate Dihydrate in the Presence of Some Metal Ions. Journal of Crystal Growth. 2007;299:146-51.
[119] Di Profio G, Curcio E, Drioli E. Supersaturation Control and Heterogeneous Nucleation in Membrane Crystallizers: Facts and Perspectives. Industrial and Engineering Chemistry Research. 2010;49:11878-89.
[120] Baohong Guan, Zhuoxian Shen, Zhongbiao Wu, Liuchun Yang, Ma X. Effect of pH preparation of Alpha-Calcium Sulfate Hemihydrate from FGD Gypsum with the Hydrothermal Method. Journal of the American Ceramic Society . 2008;91:1-6.
[121] Moussaouiti ME, Boistelle R, Bouhaouss A, Klein JP. Crystallization of Calcium Sulphate Hemihydrate in Concentrated Phosphoric Acid Solutions. Chemical Engineering Journal. 1997;68:123-30.
[122] Guan B, Fu H, Yu J, Jiang G, Kong B, Wu Z. Direct Transformation of Calcium Sulfite to α-Calcium Sulfate Hemihydrate in a Concentrated Ca-Mg-Mn Chloride Solution under Atmospheric Pressure. Fuel. 2011;90:36-41.
[123] Zhibao Li, Demopoulos GP. Solubility of CaSO Phase in Aqueous HCl + CaCl Solutions from 283K to 353K. Journal of Chemical and Engineering Data. 2005;50:1971-82.
[124] J. A. Dirksen and T. A. Ring. Fundamentals of Crystallization: Kinetic Effects on Particle Size Distributions and Morphology. Chemical Engineering Science. 1991;46:2389-427.
[125] Peng Wang E-JL, Chee-Sung Park, Byung-Ho Yoon, Du-Sik Shin, and Hyoun-Ee Kim**,. Calcium Sulfate Hemihydrate Powders with a Controlled Morphology
for Use as Bone Cement. Journal of the American Ceramic Society. 2008;91:2039-42.
[126] Hsieh CY, Tsai SP, Wang DM, Chang YN, Hsieh HJ. Preparation of γ-PGA/Chitosan Composite Tissue Engineering Matrices. Biomaterials. 2005;26:5617-23.
[127] Todd DD. Handbook of Industrial Mixing: Science and Practice. In: Paul EL, Atiemo-Obeng VA, M. KS, editors. Mixing of Highly Viscous Fluids, Polymers, and Pastes. New Jersey: J. Wiley & Son; 2004. p. 987–1025.
[128] Xu HHK, Simon Jr CG. Fast Setting Calcium Phosphate-Chitosan Scaffold: Mechanical Properties and Biocompatibility. Biomaterials. 2005;26:1337-48.
[129] Tan H, Chu CR, Payne KA, Marra KG. Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic Acid Based Hydrogels for Cartilage Tissue Engineering. Biomaterials. 2009;30:2499-506.
[130] Jin R, Moreira Teixeira LS, Dijkstra PJ, Karperien M, van Blitterswijk CA, Zhong ZY, et al. Injectable Chitosan-Based Hydrogels for Cartilage Tissue Engineering. Biomaterials. 2009;30:2544-51.
[131] Sumi VS, Kala R, Praveen RS, Prasada Rao T. Imprinted Polymers as Drug Delivery Vehicles for Metal-Based Anti-Inflammatory Drug. International Journal of Pharmaceutics. 2008;349:30-7.
[132] Karg M, Pastoriza-Santos I, Rodriguez-González B, Von Klitzing R, Wellert S, Hellweg T. Temperature, pH, and Ionic Strength Induced Changes of the Swelling Behavior of PNIPAM-poly(allylacetic acid) Copolymer Microgels. Langmuir. 2008;24:6300-6.
[133] Hong Y, Mao Z, Wang H, Gao C, Shen J. Covalently Crosslinked Chitosan Hydrogel Formed at Neutral pH and Body Temperature. Journal of Biomedical Materials Research - Part A. 2006;79:913-22.
[134] Frey G, Lu H, Powers J. Effect of Mixing Methods on Mechanical Properties of Alginate Impression Materials. Journal of Prosthodontics. 2005;14:221-5.
[135] Inoue K, Song YX, Kamiunten O, Oku J, Terao T, Fujii K. Effect of Mixing Method on Rheological Properties of Alginate Impression Materials. Journal of Oral Rehabilitation. 2002;29:615-9.
[136] Arpornmaeklong P, Pripatnanont P, Suwatwirote N. Properties of Chitosan-Collagen Sponges and Osteogenic Differentiation of Rat-Bone-Marrow Stromal Cells. International Journal of Oral and Maxillofacial Surgery. 2008;37:357-66.
[137] Peter M, Ganesh N, Selvamurugan N, Nair SV, Furuike T, Tamura H, et al. Preparation and Characterization of Chitosan-Gelatin/Nanohydroxyapatite Composite Scaffolds for Tissue Engineering Applications. Carbohydrate Polymer. 2009;80:687-94.
[138] Vishu Kumar BA, Varadaraj MC, Tharanathan RN. Low Molecular Weight Chitosan-Preparation with the Aid of Pepsin, Characterization, and Its Bactericidal Activity. Biomacromolecules. 2007;8:566-72.
[139] Wang C-C, Su C-H, Chen J-P, Chen C-C. An Enhancement on Healing Effect of Wound Dressing: Acrylic Acid Grafted and Gamma-Polyglutamic Acid/Chitosan Immobilized Polypropylene Non-Woven. Materials Science and Engineering: C. 2009;29:1715-24.
[140] No HK, Young Park N, Ho Lee S, Meyers SP. Antibacterial Activity of Chitosans and Chitosan Oligomers with Different Molecular Weights. International Journal of Food Microbiology. 2002;74:65-72.
[141] Huang S, Fu X. Cell Behavior on Microparticles with Different Surface Morphology. Journal of Alloys and Compounds. 2010;493:246-51.
[142] Zan Q, Wang C, Dong L, Cheng P, Tian J. Effect of Surface Roughness of Chitosan-Based Microspheres on Cell Adhesion. Applied Surface Science. 2008;255:401-3.
[143] Hsieh CY, Tsai SP, Wang DM, Chang YN, Hsieh HJ. Preparation of Gamma-PGA/Chitosan Composite Tissue Engineering Matrices. Biomaterials. 2005;26:5617-23.
[144] Tsao CT, Chang CH, Lin YY, Wu MF, Wang JL, Han JL, et al. Antibacterial Activity and Biocompatibility of a Chitosan-Gamma-Poly(Glutamic Acid) Polyelectrolyte Complex Hydrogel. Carbohydry Polymer. 2010;345:1774-80.
[145] Lutolf MP, Weber FE, Schmoekel HG, Schense JC, Kohler T, Muller R, et al. Repair of Bone Defects Using Synthetic Mimetics of Collagenous Extracellular matrices. Nature Biotechnology. 2003;21:513-8.
[146] Varum KM, Myhr MM, Hjerde RJN, Smidsrod O. In Vitro Degradation Rates of Partially N-Acetylated Chitosans in Human Serum. Carbohydry Polymer. 1997;299:99-101.
[147] Buescher JM, Margaritis A. Microbial Biosynthesis of Polyglutamic Acid Biopolymer and Applications in the Biopharmaceutical, Biomedical and Food Industries. Critical Reviews in Biotechnology. 2007;27:1-19.
[148] Martson M, Viljanto J, Hurme T, Saukko P. Biocompatibility of Cellulose Sponge with Bone. European Surgical Research. 1998;30:426-32.
[149] Oltramari PVP, Navarro RL, Henriques JFC, Capelozza ALA, Granjeiro JM. Dental and Skeletal Characterization of the BR-1 Minipig. Veterinary Journal. 2007;173:399-407.
[150] Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. Animal Models for Implant Biomaterial Research in Bone: A Review. European Cells and Materials. 2007;13:1-10.
[151] Palmieri A, Pezzetti F, Brunelli G, Scapoli L, Lo Muzio L, Scarano A, et al. Calcium Sulfate Acts on the miRNA of MG63E Osteoblast-Like Cells. Journal of Biomedical Materials Research - Part B Applied Biomaterials. 2008;84:369-74.
[152] Ogawa R. The Importance of Adipose-Derived Stem Cells and Vascularized Tissue Regeneration in the Field of Tissue Transplantation. Current stem cell research & therapy. 2006;1:13-20.
[153] Evans ND, Gentleman E, Polak JM. Scaffolds for Stem Cells. Materials Today. 2006;9:26-33.