過去十年，具有黏彈性的生物可降解材料的開發逐漸受到關注與歡迎，黏彈體特殊的性質被應用開發在各種領域，故黏彈體的需求也隨之大幅度上升。

基於聚（甘油癸二酸脂），加入可光固化官能基，合成出聚甘油癸二酸酯丙烯酸酯（PGSA），並添加乙酸乙烯酯（VAc）與PGSA混合共聚以增加機械性能，同時保持生物降解性。通過紫外光固化，機械性能可以更穩定，最重要的是透過積層製造聚合物的形狀可以被精密的控制，進而製造出對應形狀或造型的醫療器材。

隨著人口的持續增長，對於可以被生物降解的醫療器械還有可以用於臨床植入式的聚合物的需求一直在增加。透過光固化交聯聚合的積層製造科技提供了快速和可定制的選擇，並且得以製造具有生物相容性，生物降解性的一次性設備。

The development of biodegradable materials with elastomeric properties had become one of the most popular research topics in the past decade, and the need to produce new elastomeric polymers in large scale for a wide variety of applications had been ever increasing.

Based on the synthesis of poly (glycerol sebacate)-based photocurable biodegradable polymer, poly (glycerol sebacate) acrylate (PGSA), vinyl acetate (VAc) is added to increase the mechanical properties while maintaining the biodegradability. With UV-curing, the mechanical property can be more stable and most importantly is that the shape of polymer can be controlled by additive manufacturing.

The demand for biodegradable medical devices and implantable polymers for clinical use had been increasing along with the continuous growth of population. Biodegradable photocurable polymeric material coupling with additive manufacturing provides a fast and customizable option to make biocompatible, biodegradable and disposable devices.

Abstract I
摘要 I
致謝 II
Table of Content 1
Chapter 1 Introduction 6
1.1 Introduction to Biomaterial 6
1.1.1 Introduction to Biocompatibility 8
1.1.2 Introduction to Cells used in the Determination of Biocompatibility 9
1.1.2 Common Medical Devices 11
1.1.3 Global Use of Polymeric Materials in Medical Devices 15
1.2 Introduction to Biodegradable Polymer 16
1.2.1 Background of Biodegradable Polymer 16
1.2.2 Introduction to Biodegradation 16
1.2.3 Mechanisms of Biodegradation 16
1.2.4 Introduction to Common Biodegradable Polymers 20
1.3 Motivation and Objective 23
1.4 Introduction to Poly (Glycerol Sebecate) and Poly (Glycerol Sebacate) Acrylate 24
1.4.1 Poly (Glycerol Sebecate) (PGS) 24
1.4.2 Poly (Glycerol Sebacate) Acrylate (PGSA) 26
1.5 Introduction to Poly (Vinyl Alcohol) and Poly (Vinyl Acetate) 27
1.5.1 Co-Polymers and Blends Derived from PVA 28
1.6 Polymer Crosslinking and Film Formation 29
1.6.1 Physical Crosslinking in Polymers 29
1.6.2 Chemical Crosslinking in Polymers 29
1.7 Introduction to Additive Manufacturing 31
1.8 Introduction to Venous Thromboembolism 32
1.8.1 Risk Factors of Venous Thromboembolism 33
1.8.2 Prevention and Treatment of Venous Thromboembolism 33
Chapter 2 Experimental Methods 35
2.1 Materials and Equipment 35
2.2 Synthesis Process 37
2.2.1 Synthesis of PGS Pre-Polymer 37
2.2.2 Synthesis of PGSA Pre-Polymer and PGSA-VAc co-Polymer 37
2.3 Characterization of PGSA-VAc co-Polymer 38
2.3.1 Rheology and Viscosity Tests 38
2.3.2 Mechanical Tests 38
2.3.3 Thermal Tests 38
2.3.4 Glass Transition Temperature Measurements 39
2.3.5 Degradation Tests 39
2.3.6 Swelling Tests 39
2.3.7 Contact Angle Tests 39
2.3.8 Biocompatibility and Cytotoxicity Tests 40
2.3.9 3D-Printing System 40
Chapter 3 Results and Discussions 41
3.1 Characterization of PGSA and PGSA-VAc co-polymer 42
3.2 Rheology and Viscosity Tests 44
3.3 Tensile Test 45
3.3.1 Ultimate Tensile Strength 45
3.3.2 Elongation at Break 47
3.3.3 Young’s Modulus 48
3.4 Thermal Tests 49
3.5 Glass Transition Temperature Measurement 50
3.6 Contact Angle 51
3.7 In-vitro Cell Culture 52
3.8 Degradation Tests 53
3.9 Swelling Tests 54
3.10 Digital Light Processing (DLP) 55
Chapter 4 Conclusion 56
Chapter 5 Future Work 56
Chapter 6 Reference 57

1. Nitesh R. Patel, P.P.G., A Review on Biomaterials: Scope, Applications & Human Anatomy Significance. International Journal of Emerging Technology and Advanced Engineering, 2012. 2(4): p. 91-101.
2. Simon E Williams 'K, D.P.M., Daniel M. Horowitz, Oliver P. Peoples, PHA applications: addressing the price performance issue I Tissue engineering. International Journal of Biological Macromolecules, 1999. 25: p. 111-121.
3. Lyu, S.; Untereker, D. Degradability of Polymers for Implantable Biomedical Devices. Int. J. Mol. Sci. 2009, 10, 4033-4065.
4. Robert J. Young, Peter A. Lovell., Introduction to polymers, 3rd ed.
5. Christopher S. Brazel, S.L.R., Fundamemtal Principles of Polymeric Materials. 2012: Wiley.
6. B.L.Lopez, A.I.Mejia, L.Sierra. Biodegradability of poly(vinyl alcohol), Polymer Engineering and Science., Vol.39, 8 (1999), P.1346-1352.
7. V.Sedlarik, N.Saha, I.Kuritka, P.Saha. Environmentally friendly biocomposites based on waste of the dairy industry and poly (vinyl alcohol), Journal of Applied Polymer Science. - Vol. 106, 3 (2007), P. 1869-1879.
8. Jelinska, N & Martins, K & Tupureina, Velta & Anda, D. (2010). Poly(vinyl alcohol)/poly(vinyl acetate) blend films. Sci. J. Riga Tech. Univ. Mater. Sci. Appl. Chem.. 55-61.
9. E. Chiellini, A.Corti, S.D`Antone, R.Solaro. Biodegradation of poly (vinyl
alcohol) based materials, Progress in Polymer Science. - 28 (2003), P.963-1014
10. C.Vasile, A.K Kulshreshtha. Handbook of Polymer Blends and Composites. – Rapra Technology. - Vol. 4, 2003. P.758
11. R.Jayasekara, I.Harding, I.Bowater, G.B.Y.Christie, G.T.Lonergan.
Preparation, surface modification and characterization of solution cast
starch PVA blended films, Polymer Testing. - Vol. 23 (2004), P. 17–27.
12. Alberts B Johnson A, Lewis J, et al. Molecular biology of the cell. 4th edition.
13. C. M. Lapiere and B. V. Nusgens A., Pharmacology of the Skin I. Fibroblast, Collagen, Elastin, proteoglycans and Glycoproteins, 4th ed.
14. Perez-Basterrechea M, Esteban MM, Alvarez-Viejo M, Fontanil T, Cal S, et al. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation. PLOS ONE 12(7): e0180695.
15. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition.
16. Sunpio, B.B., J.T. Timothy Riley, and A. Dardik, Cells in focus; endothelial cell. The international Journal of Biochemistry & Cell Biology, 2006.2(2): p93-102
17. Park, H.J., et al., Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Rev, 2006.2(2): p 93-102
18. Lyu, S. and D. undereker, Degradability of polymers for implantable biomedical devices. Int J mol Sci, 2009. 10(9): p. 4033-65.
19. Lin, C.-C and K.S. Anseth, Chapter II.4.3 – The Biodegradation of Biodegrdable polymeric Biomaterials, In Biomaterials Science, 3rd edtion, P.716-728.
20. Södergård, A. and Stolt, M. Industrial Production of High Molecular Weight Poly(Lactic Acid), in Poly(Lactic Acid): Synthesis, Structures, Properties, Processing, and Applications (eds R. Auras, L.-T. Lim, S. E. M. Selke and H. Tsuji), John Wiley & Sons, Inc., Hoboken, NJ, USA.
21. Gilding, D. K.; A. M. Reed (December 1979). Biodegradable polymers for use in surgery - polyglycolic/poly (lactic acid) homo- and copolymers. Polymer. 20 (12): 1459–1464.
22. Labet, Marianne; Thielemans, Wim (2009). Synthesis of polycaprolactone: a review. Chemical Society Reviews. 38 (12): 3484–3504.
23. Basu, B. and S. Nath, Fundamentals of Biomaterials and Biocompatibility, in Adavanced Biomaterials. 2010, John wiley & Sons, Inc. p1-18.
24. Agrawal, C.M., et al., Introduction to biomaterials. Basic Theory with Engineering Application. 2013: Cambridge University Press. 419.
25. Nitesh R. Patel, P.P.G., A Review on Biomaterials: Scope, Applications & Human Anatomy Significance. International Journal of Emerging Technology and Advanced Engineering, 2012. 2(4): p. 91-101.
26. Satari, V.R., Plastics in Medical Devices Properties, Requirements and Applications., 1st edition, William Andrew, 2010.
27. Kelvin K L Wong, Jiyuan Tu, Zhonghua Sun, Don W Dissanayake, Methods in Research and Development of Biomedical Devices, Mar 2013.
28. Yuanyuan Liu, Chen Jiang, Shuai Li, Qingxi Hu, Composite vascular scaffold combining electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves structure, Journal of the Mechanical Behavior of Biomedical Materials, Volume 61, August 2016, Pages 12-25
29. Riaz Akhtar, Michael J. Sherratt, J. Kennedy Cruickshank, Brian Derby, Characterizing the elastic properties of tissues, Materials Today, Volume 14, Issue 3, March 2011, Pages 96-105
30. Lyu, S.; Untereker, D. Degradability of Polymers for Implantable Biomedical Devices. Int. J. Mol. Sci. 2009, 10, 4033-4065.
31. Azevedo, H.S.a.R., R.L., Understanding the Enzymatic Degradation of Biodegradable Polymers and Strategies to Control Their Degradation Rate, Biodegradable Systems in Tissue Engineering and Regenerative Medicine, 2005: p177-201.
32. Nasrul Wathoni, Keiichi Motoyama, Taishi Higashi, Maiko Okajima, Tatsuo Kaneko, Hidetoshi Arima, Physically crosslinked-sacran hydrogel films for wound dressing application, International Journal of Biological Macromolecules, Volume 89, August 2016, Pages 465-470
33. Hélida Gomes de Oliveira Barud, Robson Rosa da Silva, Hernane da Silva Barud, Agnieszka Tercjak, Junkal Gutierrez, Wilton Rogério Lustri, Osmir Batista de Oliveira Junior, Sidney J.L. Ribeiro, A multipurpose natural and renewable polymer in medical applications: Bacterial cellulose, Carbohydrate Polymers, Volume 153, 20 November 2016, Pages 406-420
34. John Maynard, How Wounds Heal: The 4 Main Phases of Wound Healing, http://www.shieldhealthcare.com/community/wound/2015/12/18/how-wounds-heal-the-4-main-phases-of-wound-healing/
35. C. Mauli Agrawal* and Robert B. Ray, Biodegradable polymeric scaffolds for musculoskeletal tissue engineering, Journal of Biomedical Materials Research, Volume 55, Issue 2, pages 141–150, May 2001.
36. Kyriacos A. Athanasiou, Gabriele G. Niederauer, C.Mauli Agrawal, Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/ polyglycolic acid copolymers, Biomaterials, Volume 17, Issue 2, 1996, Pages 93-102.
37. Riaz Akhtar, Michael J. Sherratt, J. Kennedy Cruickshank, Brian Derby, Characterizing the elastic properties of tissues, Materials Today, Volume 14, Issue 3, March 2011, Pages 96-105.
38. Martin, O.; Avérous, L. Poly(lactic acid): Plasticization and properties of biodegradable multiphase systems. Polymer 2001, 42, 6209–6219
39. Mi, H.-Y.; Salick, M.R.; Jing, X.; Jacques, B.R.; Crone, W.C.; Peng, X.-F.; Turng, L.-S. Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding. Mater. Sci. Eng. C 2013, 33, 4767–4776.
40. Kouya, T.; Tada, S.-i.; Minbu, H.; Nakajima, Y.; Horimizu, M.; Kawase, T.; Lloyd, D.R.; Tanaka, T. Microporous membranes of PLLA/PCL blends for periosteal tissue scaffold. Mater. Lett. 2013, 95, 103–106.
41. Dash, T.K.; Konkimalla, V.B. Poly--caprolactone based formulations for drug delivery and tissue engineering: A review. J. Control. 2012, 158, 15–33.
42. Manavitehrani, I.; Fathi, A.; Badr, H.; Daly, S.; Negahi Shirazi, A.; Dehghani, F. Biomedical Applications of Biodegradable Polyesters. Polymers 2016, 8, 20.
43. Kyriacos A. Athanasiou, Gabriele G. Niederauer and C. Mauli Agrawal, Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers, Biomoterids 17 (1996) 93-102.
44. Peter B. Maurus, Christopher C. Kaeding, Bioabsorbable implant material review, Operative Techniques in Sports Medicine, Volume 12, Issue 3, July 2004, Pages 158-160
45. Rajeev A Jain, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials, Volume 21, Issue 23, 1 December 2000, Pages 2475-2490.
46. Priya Vashisth, Vikas Pruthi, Synthesis and characterization of crosslinked gellan/PVA nanofibers for tissue engineering application, Materials Science and Engineering: C, Volume 67, 1 October 2016, Pages 304-312
47. Abraham Ulman, Formation and Structure of Self-Assembled Monolayers, Chem. Rev., 1996, 96 (4), pp 1533–1554.
48. Shuguang Zhang, Fabrication of novel biomaterials through molecular self-assembly, Nature Biotechnology, vol 21, 10 Oct 2003, p1171-1178
49. Chemistry of Crosslinking, https://www.thermofisher.com/tw/zt/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/chemistry-crosslinking.html
50. L. Calcagno, G. Compagnini, G. Foti, Structural modification of polymer films by ion irradiation, Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, Volume 65, Issue 1, 1992, Pages 413-422
51. Excell, Jon. The rise of additive manufacturing., The Engineer. 2013-10-30.
52. Standard Terminology for Additive Manufacturing – General Principles – Terminology. ASTM International. September 2013, Retrieved 2016-07-11
53. Esben Kjær Unmack Larsen, Niels B. Larsen, Kristoffer Almdal,
E. K. U. Larsen, N. B. Larsen, K. Almdal, Multimaterial Hydrogel with Widely Tunable Elasticity by Selective Photopolymerization of PEG Diacrylate and Epoxy Monomers, 8 February 2016.
54. Qi-Zhi Chen, Alexander Bismarck, Ulrich Hansen, Sarah Junaid, Michael Q. Tran, Siân E. Harding, Nadire N. Ali, Aldo R. Boccaccini, Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue, Biomaterials, Volume 29, Issue 1, January 2008, Pages 47-57
55. Ling Zhou, Hui He, Can Jiang, Shuai He, Preparation and characterization of poly(glycerol sebacate)/cellulose nanocrystals elastomeric composites, 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42196.
56. Yadong Wang, Guillermo A. Ameer, Barbara J. Sheppard, and Robert Langer, A tough biodegradable elastomer, Nature Biotechnology, volume 20,june 2002.
57. Yuan Li, George A Thouas and Qi-Zhi Chen, Biodegradable soft elastomers: synthesis/properties of materials and fabrication of scaffolds, RSC Advances
, 2012, 8229–8242
58. Christiaan L. E. Nijst , Joost P. Bruggeman , Jeffrey M. Karp , Lino Ferreira , Andreas Zumbuehl , Christopher J. Bettinger , and Robert Langer, Synthesis and Characterization of Photocurable Elastomers from Poly(glycerol-co-sebacate), Biomacromolecules, 2007, 8 (10), pp 3067–3073
59. Bioplastics market data, http://www.european-bioplastics.org/market/
60. Global Biodegradable Polymer Market Is Expected To Reach Around USD 5.18 Billion in 2020, http://www.marketresearchstore.com/news/global-biodegradable-polymer-market-208
61. A Fibroblast Cell is a connective tissue. https://www.thinglink.com/scene/578216420446306304
62. R. Dinarvand, N.Sepehri, S Manoochehri, H. Rouhani1, F. Atyabi, Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents, International Journal of Nanomedicine (default):877-95, May 2011.
63. Jaffer AK, Amin AN, Brotman DJ, Deitelzweig SB, McKean SC, Spyropoulos AC.
Prevention of venous thromboembolism in the hospitalized medical patient. Cleve
Clin J Med. 2008 Apr;75 Suppl 3:S7-16. Review. PubMed PMID: 18494223.
64. White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107:I-4-I-8. PMID: 12814979
65. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd (1998) Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year populationbased study. Arch Intern Med ,158:585–593.
66. Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US). The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville (MD): Office of the Surgeon General (US); 2008.
67. Prevention and Treatment of Venous Thromboembolism (VTE)
Site:http://www.heart.org/HEARTORG/Conditions/VascularHealth/VenousThromboembolism/Prevention-and-Treatment-of-Venous-Thromboembolism-VTE_UCM_479058_Article.jsp#.WVlC44SGOM8
68. Inferior Vena Cava Filter Placement
Site: http://emedicine.medscape.com/article/1377859-overview
69. Yasushi Tamada and Yoshito Ikadat, Fibroblast growth on polymer surfaces and biosynthesis of collagen, Journal of Biomedical Materials Research, Vol. 28, 783-789
70. Huang Han Sheng, Wang Jane; Synthesis and Characterization of Biodegradable PGS-PVA co-Polymer. Master thesis, 2015.
71. Ao-Ieong Wai-Sam, Wang Jane; Synthesis and Characterization of Photocrosslinkable Biodegradable Elastomer PGSA. Master thesis, 2015.