探討輻射對於生物可降解高分子聚合物PGS降解過程影響

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研究生：	黃國通 Huang, Kuo Tung
論文名稱：	探討輻射對於生物可降解高分子聚合物PGS降解過程影響 Effect of Radiation on the Degradation of Biodegradable PGS
指導教授：	王竹方 Wang,Chu-Fang
口試委員:	謝易恭王清海王潔
學位類別：	碩士 Master
系所名稱：	原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	73
中文關鍵詞：	PGS
外文關鍵詞：	PGS
相關次數：	點閱：3 下載：0
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聚（甘油癸二酸酯）(PGS)，是一種使用甘油和癸二酸作為原料來合成的高分子可降解聚合物。PGS具有良好的生物相容性和生物降解性的生物醫學的許多實驗室基於產品的合成。生物降解性是一種相當特殊的行為，PGS可以逐漸水解在體內或體外環境下，它可經過酶來促進水解行為。然而，有趣的是，為了瞭解PGS暴露於輻射環境下是否會影響降解行為。而輻射同時會產生自由基是一種來自輻射分解水會產生進而破壞生物組織的高活性反應物。過氧化氫也可以模擬輻射產生的自由基而不需要輻射能量。降解實驗、官能基測試和表面侵蝕進行分別自然水解、酶催化或接受輻射曝曬後的PGS，以了解其物理和化學性質的改變。進而提出假說關於輻射和自由基作用於PGS後改變的機制。這項工作預計將探討輻射環境和自由基的攻擊下，可生物降解聚合物的降解性能。

Biodegradable polymer, Poly(glycerol sebacate) (PGS), is synthesized using crude glycerol and sebacic acid as an based product on many biomedical laboratories with good biocompatibility and biodegradability. Biodegradability is a usually hydrolysis behavior of biodegradable polymer in vivo and in vitro, which can be conventionally facilitated through the enzyme treatment. However, it is interesting to understand the possibility of degradation of PGS if it is exposed by the high energy radiation. Free radical can damage tissue in biology and it come from water radiolysis. Hydrogen peroxide also can simulate free radical form water radiolysis without radiation energy. Degradation tests, functional groups tests and surface erosion were performed to characterize the mechanical and chemical properties of different PGS products after the natural hydrolysis, enzyme treatment, or radiolysis respectively. Then put forward hypotheses about the change of PGS mechanism by radiation and free radical. This work is expected to investigate the degradation performance for biodegradable polymer that might be utilized under radiation environment and free radical attacked.

Table of Contents
摘要    I
Abstract    II
Table of Contents    III
List of Figures    V
List of Tables    VII
Chapter 1 Introduction    1
1.1 General overview    1
1.2 Background    2
1.3 The Aim of this Study    4
Chapter 2 Literature Review    6
2.1 Introduction to Biomaterial    6
2.1.1 Introduction of biodegradable material    8
2.1.2 Poly(glycerol sebacate) (PGS)    9
2.1.3 Synthesis of PGS    9
2.1.4 Physico-chemical properties Properties of PGS    12
2.1.5 Biodegradation and Biocompatibility of PGS    13
2.2 Introduction to Ester Group    14
2.2.1 Hydrolysis of Ester Group    14
2.2.2 Enzyme Effect of Ester Group    15
2.3 Ionizing Radiation    17
2.3.1 Dose of Radiation    18
2.3.2 Gamma Ray , Cancer Risk and Radiation Therapy    22
2.3.3 Free radical and Biological Effects    24
3.1 Reagents and Materials    26
3.1.1 Poly(glycerol sebacate) (PGS)    26
3.1.2 In Vitro Condition    27
3.1.3 Enzyme    27
3.2 Gamma Ray System    28
3.3 Simulation of Hydrogen Peroxide    29
3.4 De sol Reaction    30
3.5 Process of Degradation Test    30
3.6 Apparatus and Device    32
3.6.1 Fourier Transform Infrared Spectroscopy (FT-IR)    32
3.6.2 Field Emission Scanning Electron Microscope (FS-SEM)    33
3.6.3 Optical Contact Angle Measuring System    34
3.6.4 Gel Permeation Chromatography (GPC)    35
3.6.5 Tensile Strength Testing Machines    36
Chapter 4 Results and Discussion    38
4.1 PGS Degradation by Different Process    38
4.1.1 Weight Loss by Radiation    39
4.1.2 Microcosmic of Radiation by Prepolymer    43
4.1.3 Hydrogen Peroxide Simulate Free Radical from Radiation    46
4.2 Proposed Degradation Mechanism by Different Process    47
4.2.1 Chemical Bonding of PGS Observed by FT-IR    47
4.2.2 Discussion on Physical Properties    51
4.2.3 Hydrophilic Changes on PGS Surface    52
4.3 PGS Degradation in Long Period    53
4.3.1 Weight Loss Observed after Radiolysis in Different Solution    54
4.3.2 PGS Surface Erosion Observed by SEM    60
Chapter 5 Conclusions    66

 
List of Figures
Figure 1-1 Forecasted Cancer Drug & Treatment Market Growth from 2013 to 2023…………………………………………………………………………………………………………………………1
Figure 1-2 Radiation Dose Examples…………………………………………………………………………5
Figure 2-1 North America cardiovascular and soft tissue patches market by application, 2012-2022, (USD Million)………………………………………………………………….7
Figure 2-2 Tow major mode of polymer degradation : bulk and surface erosion.….9
Figure 2-3 Reaction scheme for the chemical synthesis of poly(glycerol sebacate)……………………………………………………………………………………………………………11
Figure 2-4 Cross-linking scheme between two PGS polymer…………………….…………….11
Figure 2-5 Structure of Ester group…………………………………………………………………….14
Figure 2-6 The hydrolysis to ester group at Base-catalyzed ………………………………..15
Figure 2-7 Generic potential energy diagram showing the effect of a catalyst in a hypothetical exothermic chemical reaction S to P.………………………………………………16
Figure 2-8 Enzyme Replacement Results in the Acceleration Process………….……..17
Figure 2-9 Ionization Process.……………………………………………………………………………..18
Figure 2-10 The 60Co source of γ-radiation is rotated around the patient so that the common crossing point is in the tumor, concentrating the dose there. This geometric technique works for well-defined tumors…………………………………………………………….….23
Figure 3-1 Gamma Ray Co-60 Irradiation Chamber and Irradiating Architecture……..29
Figure 3-2 The whole polymer have polymer network and linear polymer………….….30
Figure 3-3 The process of PGS degradation in real radiation and PGS storage box…..31
Figure 3-4 The process of PGS degradation in H2O2 and PGS storage box………….…….32
Figure 3-5 FTIR spectrometer with an attenuated total reflectance (ATR) attachment………………………………………………………………………….………………………………….33
Figure 3-6 Image of FS-SEM (Hitachi SU 8010)…………………………….………………………….34
Figure 3-7, Image of optical contact angle measurement system(Dataphysics)…..…..34
Figure 3-8, Image of GPC instrument…………….………………………………………………………..35
Figure 3-9 Molar mass distribution……………………….…………………………………………………36
Figure 3-10 image of universal testing machine (Hegewald & Peschke)…………….…….37
Figure 4-1 PGS was de-soled and caused weight loss………………………….…………………..38
Figure 4-2 PGS weight loss after radiolysis in water and have enzyme catalyzed (a)0 day after radiolysis , 2 days before radiolysis twice and 2 days after radiolysis twice (b) Enzyme influences(2 days subtract 0 day) and radiolysis twice(2nd subtract 1st )…………………………………………………………………………………………………………………………41
Figure 4-3 SEM photograph of PGS surface irradiated in water, (a)0 gray and 0 day (b) 30 gray and 0 day……………………………………………………………………………………………………43
Figure 4-4, PGS weight loss after free radical attacked in hydrogen peroxide and have enzyme catalyzed……………………………………………………………………………………………………46
Figure 4-5 PGS structure was present by IR spectrum…………………………….……………….48
Figure 4-6 PGS irradiated in water and its C=O/C-C ratio 0 day……………….……….………49
Figure 4-7 PGS irradiated in water and its -OH/C-C ratio 0 day………………..………………49
Figure 4-8 PGS after free radical attacked in hydrogen peroxide and its C=O/C-C ratio……………………………………………………………………….……………………..…………….………….50
Figure 4-9 PGS after free radical attacked in hydrogen peroxide and its -OH/C-C ratio ……………………………………………………………………………………………………………………….51
Figure 4-10, The schematic of PGS hydrophilic changes………………………………..…………52
Figure 4-11, PGS weight loss after radiolysis in water and degraded in PBS.…………55
Figure 4-12, PGS weight loss after free radical attack form H2O2 and degraded in PBS………………………………………………………………….………………………………………………………56
Figure 4-13 PGS weight loss after radiolysis in water and degraded in PBS with enzyme catalyzed after normalize…………………………………………………………………………..58
Figure 4-14 PGS weight loss after radiolysis and degraded in PBS with enzyme catalyzed after normalize…………………………………………….………………………………………….58
Figure 4-15 PGS weight loss after free radical attack form H2O2 and degraded in PBS with enzyme catalyzed……………………………………………………………………………………………60
Figure 4-16 SEM photograph of PGS surface, (a)0 gray and after 0 day (b) 0 gray and after 7 day (c) 1 gray and after 0 day (d) 1 gray and after 7 day (e) 5 gray and after 0 day (f) 5 gray and after 7 day (g) 10 gray and after 0 day (h) 10 gray and after 7 day (i) 20 gray and after 0 day (j) 20 gray and after 7 day (k) 30 gray and after 0 day (l) 30 gray and after 7 day……………………………………………………………………………………………….62
Figure 4-17 SEM photograph of PGS sectional view, (a)0 gray and after 0 day (b) 0 gray and after 7 day (c) 1 gray and after 0 day (d) 1 gray and after 7 day (e) 5 gray and after 0 day (f) 5 gray and after 7 day (g) 10 gray and after 0 day (h) 10 gray and after 7 day (i) 20 gray and after 0 day (j) 20 gray and after 7 day (k) 30 gray and after 0 day (l) 30 gray and after 7 day…………………………………………………………………………………………..64
Figure 4-18 SEM photograph of PGS surface after free radical attack form H2O2, (a)0 gray and after 0 day (b) 0 gray and after 7 day……………………………………………………….64
Figure 4-19 SEM photograph of PGS sectional view after free radical attack form H2O2, (a)0 gray and after 0 day (b) 0 gray and after 7 day………………………………………………..65
Figure 4-18 PGS structure change mechanism by radiation and free radical……….….68
Figure 4-19 PGS structure change mechanism by free radical attack form H2O2…….68
 
List of Tables
Table 2-1 Several type of radiation source have different BRE[55]……………………….20
Table 2-2 Immediate Effects of Radiation (Adults, Whole Body, Single Exposure) [55]………………………………………………………………………………………………………….…………….21
Table 3-1 The composition of PBS (1X)………………………………..……………….…………………27
Table 3-2 The parameter of gamma ray system………………………………….……………………28
Table 3-3 The Conversion Table of Free Radical in H2O2 and Gamma Ray…..…………..29
Table 3-4 The parameter of PGS degradation…………………………………………….……………31
Table 4-1 The PGS weight loss after radiation in this study…………………….……………….42
Table 4-2 The PGS prepolycondensation 30 hour after radiation and molecular change ……………………………………………………………………………………………………….…………..45
Table 4-3 The PGS physical properties change after radiolysis…………………….…………..52
Table 4-4 The PGS content angel change after radiolysis…………………………….…………..53
Table 4-5 The PGS content angel change after free radical attack form H2O2. ………..53
Table 4-6 Linear correlation of PGS degradation by radiation…………………….……………59
Table 4-7 Linear correlation of PGS degradation by H2O2……………………………………….60 

                                

Chapter 6 Reference
1. Bettinger, C.J., Biodegradable elastomers for tissue engineering and cell-biomaterial interactions. Macromol Biosci, 2011. 11(4): p. 467-82.
2. Medhora, M., et al., Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology, 2012. 17(1): p. 66-71.
3. Sun, F., et al., Changes in Chemical Composition and Microstructure of Bamboo after Gamma Ray Irradiation. BioResources, 2014. 9(4).
4. Rosenbalm, T.N., et al., Structural and mechanical characterization of bioresorbable, elastomeric nanocomposites from poly(glycerol sebacate)/nanohydroxyapatite for tissue transport applications. J Biomed Mater Res B Appl Biomater, 2015.
5. Lim, A.J., et al., Quality of life: radical prostatectomy versus radiation therapy for prostate cancer. The Journal of urology, 1995. 154(4): p. 1420-1425.
6. Das, R., Application of nanobioceramics in bone tissue engineering. Nanobiomaterials in Hard Tissue Engineering: Applications of Nanobiomaterials, 2016: p. 353.
7. Adams, K.E., et al., Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex. Oncogene, 2006. 25(28): p. 3894-904.
8. Keyvani, V. and M.A. Kerachian, The effect of fasting on the important molecular mechanisms related to cancer treatment. J Fasting Health, 2014. 2(3): p. 113-118.
9. Cheang, M.C., et al., Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute, 2009. 101(10): p. 736-750.
10. Bachelder, E.M., et al., Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications. Journal of the American Chemical Society, 2008. 130(32): p. 10494-10495.
11. Garrison, L.P., et al., The cost-effectiveness of initial treatment of multiple myeloma in the US with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment. The oncologist, 2013. 18(1): p. 27-36.
12. Pollack, A., et al., Prostate cancer radiation dose response: results of the MD Anderson phase III randomized trial. International Journal of Radiation Oncology* Biology* Physics, 2002. 53(5): p. 1097-1105.
13. Bartelink, H., et al., Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol, 2007. 25(22): p. 3259-65.
14. Pryor, W.A., Free radical biology: xenobiotics, cancer, and aging. Annals of the New York Academy of Sciences, 1982. 393(1): p. 1-22.
15. Rokkanen, P., et al., Biodegradable implants in fracture fixation: early results of treatment of fractures of the ankle. The lancet, 1985. 325(8443): p. 1422-1424.
16. Staiger, M.P., et al., Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials, 2006. 27(9): p. 1728-1734.
17. Kajzer, A., et al., Wpływ modyfikacji powierzchni na własności fizykochemiczne tytanu stosowanego na implanty do kontaktu z krwią. Engineering of Biomaterials, 2014. 17(126): p. 23--30.
18. Hermawan, H., D. Ramdan, and J.R. Djuansjah, Metals for biomedical applications. 2011: INTECH Open Access Publisher.
19. Okazaki, Y. and E. Gotoh, Comparison of metal release from various metallic biomaterials in vitro. Biomaterials, 2005. 26(1): p. 11-21.
20. Sáenz, A., et al., Ceramic biomaterials: an introductory overview. Journal of Materials Education, 1999. 21(5/6): p. 267-276.
21. Rey, C., et al., Bone mineral: update on chemical composition and structure. Osteoporosis International, 2009. 20(6): p. 1013-1021.
22. Luengo, J.M., et al., Bioplastics from microorganisms. Current opinion in microbiology, 2003. 6(3): p. 251-260.
23. Puskas, J.E. and Y. Chen, Biomedical application of commercial polymers and novel polyisobutylene-based thermoplastic elastomers for soft tissue replacement. Biomacromolecules, 2004. 5(4): p. 1141-1154.
24. Mohanty, A., M. Misra, and G. Hinrichsen, Biofibres, biodegradable polymers and biocomposites: an overview. Macromolecular materials and Engineering, 2000. 276(1): p. 1-24.
25. Göpferich, A., Mechanisms of polymer degradation and erosion. Biomaterials, 1996. 17(2): p. 103-114.
26. Albertsson, A.-C. and I.K. Varma, Aliphatic polyesters: synthesis, properties and applications, in Degradable Aliphatic Polyesters. 2002, Springer. p. 1-40.
27. von Burkersroda, F., L. Schedl, and A. Göpferich, Why degradable polymers undergo surface erosion or bulk erosion. Biomaterials, 2002. 23(21): p. 4221-4231.
28. Valappil, S.P., et al., Biomedical applications of polyhydroxyalkanoates, an overview of animal testing and in vivo responses. Expert Review of Medical Devices, 2006. 3(6): p. 853-868.
29. Colas, A. and J. Curtis, Silicone biomaterials: history and chemistry. Biomaterials science: An introduction to materials in medicine, 2004. 2: p. 80-85.
30. Loh, X.J., A. Abdul Karim, and C. Owh, Poly(glycerol sebacate) biomaterial: synthesis and biomedical applications. J. Mater. Chem. B, 2015. 3(39): p. 7641-7652.
31. Jeon, H.J. and M.N. Kim, Biodegradation of poly(l-lactide) (PLA) exposed to UV irradiation by a mesophilic bacterium. International Biodeterioration & Biodegradation, 2013. 85: p. 289-293.
32. Rai, R., et al., Synthesis, properties and biomedical applications of poly(glycerol sebacate) (PGS): A review. Progress in Polymer Science, 2012. 37(8): p. 1051-1078.
33. Gao, J., P.M. Crapo, and Y. Wang, Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering. Tissue engineering, 2006. 12(4): p. 917-925.
34. Nguyen, V.P.N., N. Kuo, and X.J. Loh, New biocompatible thermogelling copolymers containing ethylene-butylene segments exhibiting very low gelation concentrations. Soft Matter, 2011. 7(5): p. 2150-2159.
35. Wang, Y., et al., A tough biodegradable elastomer. Nature biotechnology, 2002. 20(6): p. 602-606.
36. Jaafar, I.H., et al., Spectroscopic evaluation, thermal, and thermomechanical characterization of poly (glycerol-sebacate) with variations in curing temperatures and durations. Journal of materials science, 2010. 45(9): p. 2525-2529.
37. Robb, R.A. and H.-J. Jiang, Biomedical imaging and analysis. 1996, Google Patents.
38. Grego, A. and G. Mingrone, Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update. Clinical Nutrition, 1995. 14(3): p. 143-148.
39. Wang, Y.-X., et al., Effects of the chemical structure and the surface properties of polymeric biomaterials on their biocompatibility. Pharmaceutical research, 2004. 21(8): p. 1362-1373.
40. Gold, V., et al., Iupac compendium of chemical terminology. Blackwell Science, Oxford, 1997.
41. Bakkali, F., et al., Biological effects of essential oils–a review. Food and chemical toxicology, 2008. 46(2): p. 446-475.
42. Charton, M., Steric effects. I. Esterification and acid-catalyzed hydrolysis of esters. Journal of the American Chemical Society, 1975. 97(6): p. 1552-1556.
43. Nicolaou, K.C., et al., A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide. Angew Chem Int Ed Engl, 2005. 44(9): p. 1378-82.
44. Bender, M.L., Oxygen exchange as evidence for the existence of an intermediate in ester hydrolysis. Journal of the American Chemical Society, 1951. 73(4): p. 1626-1629.
45. Murthy, N., et al., Biodegradation of polymers. Polymer Science: A Comprehensive Reference, 2012. 9: p. 547-558.
46. Mueller, R.-J., Biological degradation of synthetic polyesters—enzymes as potential catalysts for polyester recycling. Process Biochemistry, 2006. 41(10): p. 2124-2128.
47. Walter, T., et al., Enzymatic degradation of a model polyester by lipase from Rhizopus delemar. Enzyme and microbial technology, 1995. 17(3): p. 218-224.
48. Khemani, K. and C. Scholz, Introduction and overview of degradable and renewable polymers and materials. Degradable Polymers and Materials: Principles and Practice, 2012: p. 3-10.
49. Woodside, G. and D. Kocurek, Environmental, safety, and health engineering. 1997: John Wiley & Sons.
50. Stallcup, J.G., OSHA Stallcup's? High-Voltage and Telecommunication Regulations Simplified. 2006: Jones & Bartlett Learning.
51. DeWitt, M.J. and R.J. Levis, Observing the transition from a multiphoton-dominated to a field-mediated ionization process for polyatomic molecules in intense laser fields. Physical review letters, 1998. 81(23): p. 5101.
52. Gerweck, L.E. and S.V. Kozin, Relative biological effectiveness of proton beams in clinical therapy. Radiotherapy and oncology, 1999. 50(2): p. 135-142.
53. Paganetti, H., et al., Relative biological effectiveness (RBE) values for proton beam therapy. International Journal of Radiation Oncology* Biology* Physics, 2002. 53(2): p. 407-421.
54. Workers, I., Study Group on Cancer Risk among Nuclear Industry. Direct estimates of cancer mortality due to low doses of ionising radiation: an international study, Lancet, 1994. 344: p. 1039-1043.
55. Commission, U.N.R., Office of Nuclear Regulatory Research. Division of Engineering, Component Integrity Branch: International Weld Residual Stress Round Robin Problem Statement Phase IV—Mockup, 2009.
56. Anand, P., et al., Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research, 2008. 25(9): p. 2097-2116.
57. Cardis, E., et al., Cancer consequences of the Chernobyl accident: 20 years on. Journal of radiological protection, 2006. 26(2): p. 127.
58. Radiations, N.R.C.A.C.o.t.B.E.o.I. and U.S.E.P.A.R. Office, The effects on populations of exposure to low levels of ionizing radiation: report. 1972: National Academies.
59. Real, A., et al., Effects of ionising radiation exposure on plants, fish and mammals: relevant data for environmental radiation protection. Journal of Radiological Protection, 2004. 24(4A): p. A123.
60. Beir, V., Health risks from exposure to low levels of ionizing radiation. BEIR VII phase, 2006. 2: p. 65-79.
61. Program, N.T., Ionizing radiation: x-radiation and gamma radiation. Report on carcinogens: carcinogen profiles/US Dept. of Health and Human Services, Public Health Service, National Toxicology Program, 2011. 12: p. 237.
62. Ron, E., Cancer risks from medical radiation. Health Physics, 2003. 85(1): p. 47-59.
63. Rauhut, M.M., et al., Chemiluminescence from reactions of electronegatively substituted aryl oxalates with hydrogen peroxide and fluorescent compounds. Journal of the american Chemical Society, 1967. 89(25): p. 6515-6522.
64. da Silva Aquino, K.A., Sterilization by gamma irradiation. 2012: INTECH Open Access Publisher.
65. Naidu, S.K., E.E. Klaus, and J.L. Duda, Evaluation of liquid phase oxidation products of ester and mineral oil lubricants. Industrial & engineering chemistry product research and development, 1984. 23(4): p. 613-619.

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