臺灣博碩士論文加值系統

機械性響應的水凝膠在生物支架中表現出很大的潛能，但傳統的水凝膠在作為仿生支架時，依舊會遇到動態特徵以及網目尺寸的問題，所以我們嘗試結合動態鍵結所組成的三維網目結構和擁有特殊物理結構的材料當作填充物組成新的複合水凝膠，因此為了符合我們的設計概念，我們先結合殼聚醣和戊二醛反應所得動態席氏夫鍵結所組成的纖維網目，並選擇擁有自組裝特性的F127作為填充纖維網目的材料。

在本文中，首先在應變掃描測試中觀察到F127/殼聚醣/戊二醛複合水凝膠系統中戊二醛濃度與凝膠溶膠間轉變的關係，並在非線性流變學中展現出應變硬化的特性，接著我們利用流變-小角X光散射技術探討非線性行為與微結構變化間的關係，因此可以得知F127/殼聚醣/戊二醛複合水凝膠的應變硬化行為與纖維網目對微胞結構的空間侷限性有關連性。

最後，我們著重於F127/殼聚醣/戊二醛複合水凝膠的機械性質，首先黏彈性質對於生物支架在細胞匹配上是相當重要，在此研究利用應力鬆弛測試並求得複合水凝膠的鬆弛時間，並得到鬆弛時間與纖維網目的空間侷限性有相關，另一方面，自癒能力為仿生支架的另一個重點，而在循環測驗中得到F127/殼聚醣/戊二醛複合水凝膠確實有著自癒特性。

Mechano-responsive hydrogels offer excellent advantages for biomedical applications. However, the conventional hydrogels still encounter dynamic features and mesh size problems when mimics the natural extracellular matrix. Therefore, we tried to develop a new composite hydrogel, which combines the three-dimensional network structure formed by dynamic bonding and the material with a unique physical structure as filler. First, to satisfy our design concept, we combined chitosan and glutaraldehyde to form the dynamic Schiff-base linkage. Then, we selected F127 with self-assembly property as the filler material.

In this study, the strain sweep test observed the relationship between glutaraldehyde concentration and gel-sol transition in the F127/chitosan/glutaraldehyde composite hydrogel system. Then, in the nonlinear rheology, the composite system demonstrated the strain stiffening behavior opposite the strain-softening behavior of F127. Finally, we investigate the relationship between the nonlinear behavior and microstructural changes by in-situ Rheo-SAXS. It can be concluded that the strain-stiffening behavior of F127/chitosan/glutaraldehyde composite hydrogel is related to the fiber network spatial confinement of the micelle structure.

Finally, we focused on the mechanical properties of F127/chitosan/glutaraldehyde composite hydrogel. Firstly, viscoelastic properties are essential for the cellular matching of bioscaffolds. In this study, the stress relaxation test determined the relaxation time of the composite hydrogel—the relaxation time correlated with the spatial limitation of the fibrous mesh.On the other hand, the self-healing ability of the bionic scaffold is a critical point. In the cyclic test, the F127/chitosan/glutaraldehyde composite hydrogel did have self-healing properties.

Abstract............... III
Acknowledgements....... IV
Contents............... V
Chart Catalogues....... VII
Principal Notation..... X
Chapter 1. Introduction........................................... 1
1.1. Structural Characteristics and Applications of Hydrogel ........1
1.2. Biological Properties of Chitosan and its Fibrous Network...... 2
1.3. Structural Characteristics of Self-assembling F127............. 3
1.4. The Development and Application of in situ Rheo-SAXS........... 7
Chapter 2. Experimental Section................................... 10
2.1. Materials...................................................... 10
2.2. Preparation Method............................................. 10
2.2.1. Preparation of chitosan/ GA Hydrogel........................... 10
2.2.2. Preparation of F127 Hydrogel................................... 11
2.2.3. Preparation of chitosan/ GA/F127 Hydrogel...................... 11
2.3. Rheological Measurement........................................ 11
2.4. Dynamic oscillatory shear test................................. 12
2.4.1. Small Amplitude Oscillation Shear(SAOS) ...................... 13
2.4.2. Large Amplitude Oscillation Shear(LAOS) ........................15
2.5. In situ Rheo-SAXS.............................................. 17
Chapter 3. Results and discussion................................. 18
3.1. Rheological properties of F127 self-assembly material, chitosan/GA fiber network, and F127/chitosan/GA composite hydrogel....................... 18
3.2. Rheo-SAXS for F127 self-assembly material, chitosan/GA fiber network, and F127/chitosan/GA composite hydrogel.................................... 29
3.3Stress relaxation and self-healing ability of F127 self-assembly material, chitosan/GA fiber network, and F127/chitosan/GA composite hydrogel..... 39
Chapter 4. Conclusion............................................. 43
References............................................................. 44

(1) A. S. Hoffman, Adv Drug Deliver Rev 64, 18 (2012) (2) O. Wichterle, D. Lim, Nature 185, 117(1960)
(3) M. Vatankhah-Varnosfaderani, A. N. Keith, Y. Cong, H. Liang, M. Rosenthal, M. Sztucki, C. Clair, S. Magonov, D. A. Ivanov, A. V. Dobrynin, and S. S. Sheiko, Science 359, 1509 (2018).
(4) J. A. Syrett, C. R. Becer, and D. M. Haddleton, Polym Chem-Uk 1, 978 (2010).
(5) J. Chen, Q. Peng, X. Peng, L. Han, X. Wang, J. Wang, and H. Zeng, Acs Appl Polym Mater 2, 1092 (2020).
(6) J. A. Sowjanya, J. Singh, T. Mohita, S. Sarvanan, A. Moorthi, N. Srinivasan, and N. Selvamurugan, Colloids Surfaces B Biointerfaces 109, 294 (2013).
(7) S. Saravanan, D. K. Sameera, A. Moorthi, and N. Selvamurugan, Int J Biol Macromol 62, 481 (2013).
(8) A. M. Rosales and K. S. Anseth, Nat Rev Mater 1, 15012 (2016).
(9) P. Sacco, F. Furlani, G. de Marzo, E. Marsich, S. Paoletti, and I. Donati, Prog Coll Pol Sci S 4, 67 (2018).
(10) J. Berger, M. Reist, J. M. Mayer, O. Felt, N. A. Peppas, and R. Gurny, Eur J Pharm Biopharm 57, 19 (2004).
(11) B. B. Mandal and S. C. Kundu, Biomaterials 30, 2956 (2009)
(12) Y.-J. Ren, H. Zhang, H. Huang, X.-M. Wang, Z.-Y. Zhou, F.-Z. Cui, and Y.-H. An, Biomaterials 30, 1036 (2009).
(13) E. Russo and C. Villa, Pharm 11, 671 (2019).
(14) W. Loose and B. J. Ackerson, J Chem Phys 101, 7211 (1994).
(15) J. Jiang, C. Burger, C. Li, J. Li, M. Y. Lin, R. H. Colby, M. H. Rafailovich, and J. C. Sokolov, Macromolecules 40, 4016 (2007).
(16) K. Hyun, J. G. Nam, M. Wilhellm, K. H. Ahn, and S. J. Lee, Rheol Acta 45, 239 (2006).
(17) B. J. Ackerson and P. N. Pusey, Physical Review Letter 61, 1033(1988).
(18) M. Morishita, J. M. Barichello, K. Takayama, Y. Chiba, S. Tokiwa, and T. Nagai, Int J Pharmaceut 212, 289 (2001).
(19) K. Huang, B. P. Lee, D. R. Ingram, and P. B. Messersmith, Biomacromolecules 3, 397 (2002).
(20) I. Holland, J. Logan, J. Shi, C. McCormick, D. Liu, and W. Shu, Bio-Design Manuf 1, 89 (2018).
(21) Texter J,Schwarz R. Polym Preprints 46, 1238 (2005)
(22) K. H. Sun, Y. S. Sohn, and B. Jeong, Biomacromolecules 7, 2871 (2006).
45
(23) C. Wu and G. Schmidt, Macromol Rapid Comm 30, 1492 (2009).
(24) Y. Lee, H. J. Chung, S. Yeo, C.-H. Ahn, H. Lee, P. B. Messersmith, and T. G. Park, Soft Matter 6, 977 (2010).
(25) M. Gori, S. M. Giannitelli, M. Torre, P. Mozetic, F. Abbruzzese, M. Trombetta, E. Traversa, L. Moroni, and A. Rainer, Adv Healthc Mater 9, 2001163 (2020)
(26) T. Meins, K. Hyun, N. Dingenouts, M. F. Ardakani, B. Struth, and M. Wilhelm, Macromolecules 45, 455 (2012).
(27) B. Pulamagatta, S. Pankaj, M. Beiner, and W. H. Binder, Macromolecules 44, 958 (2011).
(28) P. Panine, M. Gradzielski, and T. Narayanan, Rev Sci Instrum 74, 2451(2003)
(29) V. Räntzsch, M. B. Özen, K. Ratzsch, E. Stellamanns, M. Sprung, G. Guthausen, and M. Wilhelm, Macromol Mater Eng 304, 1800586 (2019).
(30) A. Keller, E. Pedemonte, and F. M. Willmouth, Kolloid-Zeitschrift Und Zeitschrift Für Polym 238, 385 (1970).
(31) G. Shin, N. Sakamoto, K. Saijo, S. Suehiro, T. Hashimoto, K. Ito, and Y. Amemiya, Macromolecules 33, 9002 (2000).
(32) K. Saijo, G. Shin, T. Hashimoto, Y. Amemiya, and K. Ito, Macromolecules 46, 1549 (2013).
(33) B. Shriky, A. Kelly, M. Babenko, N. Mahoudi, S. Rogers, O. Shebanova, T. Snow, and T. Gough, Joural of Collidal and Interface Science565,119 (2020).
(34) B. J. Ackerson and P. N. Pusey, Physical Review Letter 61,1033(1988).
(35) K. Hyuna, M. Wilhelmb, C.O. Kleinb, K. S. Choc, J. Gu Namd, K. H. Ahnd, S. J. Leed, R. H. Ewoldte, G. H. McKinleyf, Progress in Polymer Science 36,1697 (2011)
(36) T.G.Meger,The rheology hand book: for users of rotations and oscillatory rheometers.:Vicent Network Gmbh&CO KG(2006).
(37) N.W. Tschoegl. The phenomenological theory of linear viscoelasticbehavior: an introduction.:New York: Springer-Verlag; (1989).
(38) J.M. Dealy, K.F.Wissbrun .Melt rheology and its role in plastics processing:theory and applications. New York: VNR(1990).
(39) T. ‐T Tee and J. M. Dealy, T Soc Rheol 19, 595 (1975).
(40) R. H. Ewoldt, A. E. Hosoi, and G. H. McKinley, J Rheol 52, 1427 (2008).
(41) K. Hyun, J. G. Nam, M. Willhelm, K. H. Ahn, and S. J. LEE, Kroea-Australia Rheology Joural15 ,97(2003).
(42) M. W. Liberatore, F. Nettesheim, N. J. Wagner, and L. Porcar, Phys Rev E 73, 020504 (2006).
(43) Y.-J. Lin, W.-T. Chuang, and S. Hsu, Acs Macro Lett 8, 1449 (2019).
(44) F. Furlani, A. Marfoglia, E. Marsich, I. Donati, and P. Sacco, Biomacromolecules 22, 2902 (2021).
(45) S. Karato, Phys Rev B 79, 214106 (2009).
(46) M. L. Young, J. D. Almer, M. R. Daymond, D. R. Haeffner, and D. C. Dunand, Acta Mater 55, 1999 (2007).
(47) L. Wang, M. Li, and J. Almer, J Nucl Mater 440, 81 (2013).
(48) S. Cheng, Y. D. Wang, H. Choo, X.-L. Wang, J. D. Almer, P. K. Liaw, and Y. K. Lee, Acta Mater 58, 2419 (2010).
(49) O. Chaudhuri, L. Gu, D. Klumpers, M. Darnell, S. A. Bencherif, J. C. Weaver, N. Huebsch, H. Lee, E. Lippens, G. N. Duda, and D. J. Mooney, Nat Mater 15, 326 (2016).
(50) O. Chaudhuri, L. Gu, M. Darnell, D. Klumpers, S. A. Bencherif, J. C. Weaver, N. Huebsch, and D. J. Mooney, Nat Commun 6, 6365 (2015).
(51) A. V. Tobolsky, B. A. Dunell, and R. D. Andrews, Text Res J 21, 404 (1951).
(52) J. Xu, Y. Liu, and S. Hsu, Molecules 24, 3005 (2019).
(53) M. Vahedi, J. Barzin, F. Shokrolahi, and P. Shokrollahi, Macromol Mater Eng 303, 1800200 (2018).
(54) H. Meng, P. Xiao, J. Gu, X. Wen, J. Xu, C. Zhao, J. Zhang, and T. Chen, Chem Commun 50, 12277 (2014).