臺灣博碩士論文加值系統

此研究發表一個由氫氧基磷灰石(HAp)均勻分散於甲基丙烯酸羟乙酯(HEMA)、乙二醇二甲基丙烯酸酯(EGDMA)、海藻酸鈉(ALG)混合水溶液所組成的新型半雙網絡水凝膠(S-DN)骨修復生物材料。該材料之機械性質、含水量、收縮度與形態學皆被調查。在這之中，ALG/HEMA-HAp 10%乾凝膠顯示出高達16.378MPa的拉伸應力，且其伸長度為4.61%，可相當於人體小梁骨的機械性質。最終我們添加Irgacure 127 1.00wt%和Kemisorp 11S 0.04 wt%，使用光固化3D列印機SWIM-ER成功列印出3D立體骨頭造型ALG/HEMA-HAp。

A new bone repairing biomaterial, ALG/HEMA-HAp, was a semi-double network (S-DN) hydrogel fabricated from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) in the aqueous mixed dispersion of hydroxyapatite (HAp) and sodium alginate (ALG). The mechanical properties, moisture, shrinkage and morphology of all samples were investigated. Among them, The ALG/HEMA-HAp 10% xerogel showed the stress is 16.378 MPa and the elongation is 4.61%, which might be comparable to the human’s trabecular having the tensile strength of 10 to 20 MPa and elongation of 5% to 7%. Finally, we use Stereolithographic 3D Printer SWIM-ER, and then succeed to print out a 3D bone shape after adding Irgacure 127 1.00wt% and Kemisorp 11S 0.04 wt%.

Abstract i
Table of contents ii
List of figures v
List of tables vii

Chapter 1 INTRODUCTION 1
1.1 Bone Regeneration Engineering 1
1.1.1 Development of Bone Regeneration Medicine 2
1.1.2 Human’s Bone 2
1.1.2.1 Composition of Bones 2
1.1.2.2 Structures of Bones 3
1.1.2.3 Mechanical properties of Bones 4
1.2 Bone Repair Biomaterials 5
1.2.1 Design concept for Bone scaffolds 5
1.2.2 Metallic Scaffolds 5
1.2.3 Polymeric Scaffolds 6
1.2.3.1 Natural polymers 6
1.2.3.2 Synthetic polymers 7
1.2.4 Ceramic Scaffolds 7
1.3 Semi-Double Network (S-DN) hydrogel 8
1.3.1 Interpenetrating Polymer Network (IPN) 8
1.3.2 Semi-Double Network Bone Scaffold Design 9

Chapter 2 EXPERIMENTAL 10
2.1 Materials and Instruments 10
2.1.1 Reagents 10
2.1.2 Instruments 10
2.2 Precursor Solution Preparation 13
2.2.1 ALG − HAp composite films 13
2.2.2 HEMA hydrogels/xerogels 13
2.2.3 ALG/HEMA − HAp hydrogels/xerogels 14
2.2.4 ALG/HEMA – HAp Precursor Solution for Stereolithographic 3D Printing 14
2.3 Stereolithographic 3D Printing 15
2.3.1 Printing Speed Text 15
2.3.2 Printing Process of 2D and 3D 15

Chapter 3 RESULTS AND DISCUSSION 17
3.1 Phase Separation Problem 17
3.1.1 The Maximum content of ALG 17
3.1.2 The Maximum content of HAp 18
3.1.3 The best ratio between HEMA and H2O 19
3.1.4 Initiator 20
3.2 Mechanical Properties and Morphological Examination 21
3.2.1 Effect of Semi-Double Network to Mechanical Properties 21
3.2.2 Effect of HAp content to Mechanical Properties 23
3.2.3 Effect of EGDMA content to Mechanical Properties 28
3.3 Moisture and Shrinkage 32
3.3.1 Effect of HAp content to Moisture and Shrinkage 32
3.3.2 Effect of EGDMA content to Moisture and Shrinkage 33
3.4 Stereolithographic 3D Printing 34
3.4.1 Printing Speed Text 34
3.4.2 3D Printing for ALG/HEMA – HAp hydrogel 35
3.4.3 Shrinkage of 3D printing Bone Shape 36

Chapter 4 CONCLUSIONS 37
References 38
Appendix – Presentation Award 42

1. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004. Available from: http://www.ncbi.nlm.nih.gov/books/NBK45502/
2. Johnell, O.; Kanis J. A., An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporosis International. 2006, 17(12), 1726-1733.
3. Joseph Melton, L.; Chrischilles, Elizabeth A.; Cyrus Cooper; Lane, Ann W.; Lawrence Riggs, B., Perspective How Many Women Have Osteoporosis? Journal of Bone and Mineral Research. 2009, 7(9), 1005-1010.
4. Seeley, D.G.; Browner, W.S.; Nevitt, M.C.; Genant, H.K.; Scott, J.C.; Cummings, S.R., Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1991, 115(11), 837-842.
5. Campana, V.; Milano, G.; Pagano, E.; Barba, M.; Cicione, C.; Salonna, G.; Lattanzi, W.; Logroscino, G., Bone substitutes in orthopaedic surgery from basic science to clinical practice. Journal of Materials Science Materials in Medicine. 2014, 25(10), 2445-2461.
6. Ikeda, T.; Nakamura, T.; Fujimoto, T.; Kikuchi, T.; Takagi, K., Morbidity at Iliac Bone Graft Donor Sites. Orthopedics & Traumatology, 2000, 49(3), 666-668.
7. Guthoff, R.; Katowitz, J. A., Risk of Infectious Disease Transmission Through Use of Allografts. Oculoplastics and Orbit (Essentials in Ophthalmology), 2006, 3-18.
8. Yeni, Y.N.; Brown, C.U.; Norman, T.L., Influence of Bone Composition and Apparent Density on Fracture Toughness of the Human Femur and Tibia. Bone, 1998, 22(1), 79-84
9. Woodard, H.Q., The Elementary Composition of Human Cortical Bone. Health Physics, 1962, 8(5), 513-517
10. Gong, J.K.; Arnold, J.S.; Cohn, S.H., The Anatomical Record, 1964, 149(3), 325–331
11. Krejci I.; Albert, P.; Lutz, F., The Influence of Antagonist Standardization on Wear. Journal of Dental Research, 1999, 78(2), 713–719.
12. Landis, W.J., The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. Bone, 1995, 16(5), 533-544.
13. Baohua, Ji. Huajian, Gao., Mechanical properties of nanostructure of biological materials. Journal of the Mechanics and Physics of Solids, 2004, 52(9), 1963-1990.
14. Jäger, I.; Fratzl, P., Mineralized Collagen Fibrils: A Mechanical Model with a Staggered Arrangement of Mineral Particles. Biophysical Journal, 2000, 79(4), 1737-1746.
15. Orlovskii,V.P.; Komlev, V.S.; Barinov, S.M., Hydroxyapatite and Hydroxyapatite-Based Ceramics. Inorganic Materials, 2002, 38(10), 973–984.
16. Hirsch, C.; Evans, F.G., Studies On Some Physical Properties of Infant Compact Bone. Acta Orthopaedica Scandinavica, 1965, 35(1-4), 300-313.
17. Bandyopadhyay-Ghosh, S., Bone as a Collagen-hydroxyapatite Composite and its Repair. Trends Biomater. Artif. Organs, 2008, 22(2), 116-124.
18. Albrektsson, T.; Johansson, C., Osteoinduction, osteoconduction and osseointegration. European Spine Journal, 2001, 10(0), S96-S101.
19. Barradas, A.M.C.; Yuan, H.; van Blitterswijk, C.A.; Habibovic, P., Osteoinductive biomaterials: current knowledge of properties, experimental models and biological mechanisms. European Cells and Materials, 2011, 21, 407-429.
20. Matassi, F.; Nistri, Lorenzo.; Paez, D.C.; Innocenti, M. New biomaterials for bone regeneration. Clin Cases Miner Bone Metab, 2011, 8(1), 21-24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230919/?report=classic
21. Wang, F.; Wang, L.; Feng, Y.; Yang, X.; Ma, Z.; Shi, L.; Ma, X.; Wang, J.; Ma, T.; Yang, Z.; Wen, X.; Zhang, Y.; Lei, W., Evaluation of an artificial vertebral body fabricated by a tantalum-coated porous titanium scaffold for lumbar vertebral defect repair in rabbits. Scientific Reports, 2018, 8(1).
22. Venkatesan, J.; Nithya, R.; Sudha, P.N.; Kim, S.K., Role of Alginate in Bone Tissue Engineering. Advances in Food and Nutrition Research, 2014, 73, 45-57.
23. Zhang, Y.; Chu, D.; Zheng, M.; Kissel, T.; Agarwal, S., Biocompatible and degradable poly(2-hydroxyethyl methacrylate) based polymers for biomedical applications. Polymer Chemistry, 2012, 3(10), 2752.
24. Kattimani, V.S.; Kondaka, S.; Lingamaneni, K.P.; Hydroxyapatite—Past, Present, and Future in Bone Regeneration. Bone and Tissue Regeneration Insights, 2016, 7, 9-19.
25. Klempner, D.; Sperling, L.H.; Utracki, L.A., Interpenetrating Polymer Networks: An Overview. Interpenetrating Polymer Networks (Advances in Chemistry), 1994, 239, 3-38.
26. Dragan, E.S., Design and applications of interpenetrating polymer network hydrogels. A review. Chemical Engineering Journal, 2014, 243, 572-590.
27. Naficy, S.; Kawakami, S.; Sadegholvaad, S.; Wakisaka, M.; Spinks, G.M., Mechanical properties of interpenetrating polymer network hydrogels based on hybrid ionically and covalently crosslinked networks. Journal of Applied Polymer Science, 2013, 130(4), 2504-2513.
28. Kausar, A.; Polyurethane/Epoxy Interpenetrating Polymer Network. Aspects of Polyurethanes, 2017.
29. Kebede, M.A.; Asiku, K.S.; Imae, T.; Kawakami, M.; Furukawa, H.; Wu, C.M., Stereolithographic and molding fabrications of hydroxyapatite-polymer gels applicable to bone regeneration materials. Journal of the Taiwan Institute of Chemical Engineers. 2018, 92, 91-96.
30. Gulsen, G.; Chauhan, A. Effect of water content on transparency, swelling, lidocaine diffusion in p-HEMA gels. Journal of Membrane Science, 2006, 269(1-2), 35-48.
31. Jang, H.L.; Lee, H.K.; Jin, K.; Ahn, H.Y; Lee, H.E;, Nam, K.T, Phase transformation from hydroxyapatite to the secondary bone mineral, whitlockite. Journal of Materials Chemistry B, 2015, 3(7), 1342-1349.
32. Gleeson, J.P.; Plunkett, N.A; O’Brien, F.J; Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration. European Cells and Materials, 2010, 20, 218-230.