臺灣博碩士論文加值系統

在本論文中, 我們成功的展示了基於肽和聚合物組合的熱響應超分子雙網絡 (DN) 纖維水凝膠. 它分為兩部分在第一部分, 我們發現5F-FF和聚 (乙二醇) (PEG) 的有效形成共組合雙網絡納米纖維和pH7.0的水凝膠的重量百分比率. 5F-FF作為平均直徑寬度為15 ± 1nm的第一個光纖網絡, PEG作為第二個光纖網絡, 平均直徑寬度為5±1 nm. 熱分析超分子DN系統不僅增強了凝膠的機械性能, 而且與單獨的5F-FF纖維單網 (SN) 相比, 增強了其穩定性和增強了細胞存活率. 重量比為0.5:4.5 wt % 的5F-FF/PEG1500, 2000和3000水凝膠是生物相容的, 因此它能夠用作生物醫學應用的良好潛在的腳手架材料.
在第二部分, 我們研究了氟原子總數對肽分子的DN末端部分的極大影響, 以更好地了解製造熱反應超分子DN水凝膠. 減少氟原子的總數將降低芳香族π-π相互作用的疏水性和能量結合強度. 3F-FF/PEG, 1F-FF/PEG, 和0F-FF/PEG中的每一種可以經歷水凝膠的溶液, 但是它們在共組裝和水凝膠化時間上具有不同的性質. 通過研究nF-FF/肽水凝膠系統的共同組裝, 我們可以找到適合基於細胞的生物醫學應用的有希望的候選者.

In this thesis, we successfully demonstrated the thermoreversible supramolecular double-network (DN) fiber hydrogel based on the combination of peptide and polymer. It is divided into two part; in the first part, we discovered that weight percentage ratio of 5F-FF and poly (ethylene glycol) (PEG) efficiently formed co-assembled double network nanofibers and the hydrogel at pH 7.0. The 5F-FF acts as the first fiber network with average diameter width 15 ± 1 nm, while PEG as the second fiber network with average diameter width 5 ± 1 nm. The thermoresponsive supramolecular DN system is not only enhanced the mechanical performance of the gel but also enhanced its stability and enhanced the cell survival ratio compared to fiber single network (SN) of 5F-FF alone. The 5F-FF/PEG1500, 2000, and 3000 hydrogels with weight percentage ratios of 0.5:4.5 wt % are biocompatible, therefore its able to use as good potential scaffolding materials for biomedical applications.
In the second part, we studied the greatly influence of total number of fluorine atoms on N-terminus moiety of peptide molecules to get better insight of fabricating thermoresponsive supramolecular DN hydrogel. Reducing the total number of fluorine atom will reduce the hydrophobicity and energy binding strength of aromatic π-π interactions. Each of 3F-FF/PEG, 1F-FF/PEG, and 0F-FF/PEG could undergo solution to hydrogel, but each of it has different properties on co-assembly and hydrogelation time. By studying the co-assembly of nF-FF/peptide hydrogel system, we could find the promising candidate which is suitable for cell-based biomedical applications.

Chinese Abstract i
English Abstract ii
Acknowledgement iii
Table of Content iv
List of Table vi
List of Figure vii
Chapter 1 Introduction 1
1.1 Supramolecular Hydrogel 1
1.1.1 Hydrogels 1
1.1.2 Classifications of hydrogels 2
1.2 Themoresponsive Hydrogel 3
1.2.1 Thermoresponsive Hydrogel Classification 4
1.2.1.1 Sol-Gel-Sol Versus Gel-Sol Behavior 4
1.2.1.2 Gel-Sol Transition Behavior 5
1.2.1.3 Recently Thermoresponsive Hydrogel 6
1.2.1.3.1 Pluronic F127 6
1.2.1.3.2 F127/HA Polymer 7
1.2.1.3.3 Peptide-PEG 8
1.3 Supramolecular Double Network Hydrogel 10
1.3.1 Double Network Hydrogel 10
1.3.2 Method of Preparation 11
1.3.3 Structure 11
1.4 Thermoresponsive Double Network Hydrogel 12
1.4.1 Peptide/Polysaccharide 12
1.4.2 Alginate/poly(N-iso-propylacrylamide)-poly(ethylene glycol) 13
1.5 Conclusions 15
Chapter 2 Thermoreversible Supramolecular Double Network Hydrogel Based on 5F-FF and Poly (ethylene glycol)
16
2.1 Introduction 16
2.2 Experimental section 18
2.3 Results and discussion 24
2.4 Summary 43
Chapter 3 The influence of the total number of fluorine atom on themorenponsive supramolecular DN hydrogel
44
3.1 Introduction 44
3.2 Experimental section 46
3.3 Results and discussion 54
3.4 Summary 67
Chapter 4 Conclusions 69
References 70
Appendices 73
Autobiography 78

[1] J. Liu, H. Song, L. Zhang, H. Xu, and X. Zhao, "Self-Assembly-Peptide Hydrogels as Tissue-Engineering Scaffolds for Three-Dimensional Culture of Chondrocytes in vitro," Macromolecular Bioscience, vol. 10, pp. 1164-1170, 2010.
[2] R. Huang, W. Qi, L. Feng, R. Su, and Z. He, "Self-assembling peptide-polysaccharide hybrid hydrogel as a potential carrier for drug delivery," Soft Matter, vol. 7, pp. 6222-6230, 2011.
[3] Y. Li, F. Wang, and H. Cui, "Peptide-based supramolecular hydrogels for delivery of biologics," Bioengineering & Translational Medicine, vol. 1, pp. 306-322, 2016.
[4] C. K. Thota, N. Yadav, and V. S. Chauhan, ""A novel highly stable and injectable hydrogel based on a conformationally restricted ultrashort peptide"," Sci Rep, vol. 6, p. 31167, Aug 10 2016.
[5] X. Du, J. Zhou, J. Shi, and B. Xu, "Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials," Chemical Reviews, vol. 115, pp. 13165-13307, 2015/12/23 2015.
[6] J. Yan, B. S. Wong, and L. Kang, "Molecular Gels for Tissue Engineering," in Soft Fibrillar Materials, ed: Wiley-VCH Verlag GmbH & Co. KGaA, 2013, pp. 129-162.
[7] H. Fenniri, P. Mathivanan, K. L. Vidale, D. M. Sherman, K. Hallenga, K. V. Wood, et al., "Helical Rosette Nanotubes:  Design, Self-Assembly, and Characterization," Journal of the American Chemical Society, vol. 123, pp. 3854-3855, 2001/04/01 2001.
[8] J. H. Fuhrhop and W. Helfrich, "Fluid and solid fibers made of lipid molecular bilayers," Chemical Reviews, vol. 93, pp. 1565-1582, 1993/06/01 1993.
[9] A. N. Moore and J. D. Hartgerink, "Self-Assembling Multidomain Peptide Nanofibers for Delivery of Bioactive Molecules and Tissue Regeneration," Accounts of Chemical Research, vol. 50, pp. 714-722, 2017/04/18 2017.
[10] J. Huang, C. L. Hastings, G. P. Duffy, H. M. Kelly, J. Raeburn, D. J. Adams, et al., "Supramolecular Hydrogels with Reverse Thermal Gelation Properties from (Oligo)tyrosine Containing Block Copolymers," Biomacromolecules, vol. 14, pp. 200-206, 2013/01/14 2013.
[11] N. Higashi, R. Sonoda, and T. Koga, "Thermo-responsive amino acid-based vinyl polymers showing widely tunable LCST/UCST behavior in water," RSC Advances, vol. 5, pp. 67652-67657, 2015.
[12] S. Ashraf, H.-K. Park, H. Park, and S.-H. Lee, "Snapshot of phase transition in thermoresponsive hydrogel PNIPAM: Role in drug delivery and tissue engineering," Macromolecular Research, vol. 24, pp. 297-304, 2016/04/01 2016.
[13] H. H. Nguyen, B. Payré, J. Fitremann, N. Lauth-de Viguerie, and J.-D. Marty, "Thermoresponsive Properties of PNIPAM-Based Hydrogels: Effect of Molecular Architecture and Embedded Gold Nanoparticles," Langmuir, vol. 31, pp. 4761-4768, 2015/04/28 2015.
[14] Y.-s. Jung, W. Park, H. Park, D.-K. Lee, and K. Na, "Thermo-sensitive injectable hydrogel based on the physical mixing of hyaluronic acid and Pluronic F-127 for sustained NSAID delivery," Carbohydrate Polymers, vol. 156, pp. 403-408, 1/20/ 2017.
[15] I. W. Velthoen, E. J. Tijsma, P. J. Dijkstra, and J. Feijen, "Thermo-Responsive Hydrogels Based on Branched Poly(L-lactide)-poly(ethylene glycol) Copolymers," Macromolecular Symposia, vol. 272, pp. 13-27, 2008.
[16] H. J. Zhang, T. L. Sun, A. K. Zhang, Y. Ikura, T. Nakajima, T. Nonoyama, et al., "Tough Physical Double-Network Hydrogels Based on Amphiphilic Triblock Copolymers," Advanced Materials, vol. 28, pp. 4884-4890, 2016.
[17] B. Jeong, Y. H. Bae, and S. W. Kim, "Thermoreversible Gelation of PEG−PLGA−PEG Triblock Copolymer Aqueous Solutions," Macromolecules, vol. 32, pp. 7064-7069, 1999/10/01 1999.
[18] S. Xuan, C.-U. Lee, C. Chen, A. B. Doyle, Y. Zhang, L. Guo, et al., "Thermoreversible and Injectable ABC Polypeptoid Hydrogels: Controlling the Hydrogel Properties through Molecular Design," Chemistry of Materials, vol. 28, pp. 727-737, 2016/02/09 2016.
[19] E. Gioffredi, M. Boffito, S. Calzone, S. M. Giannitelli, A. Rainer, M. Trombetta, et al., "Pluronic F127 Hydrogel Characterization and Biofabrication in Cellularized Constructs for Tissue Engineering Applications," Procedia CIRP, vol. 49, pp. 125-132, 2016/01/01/ 2016.
[20] C. Weinand, I. Pomerantseva, C. M. Neville, R. Gupta, E. Weinberg, I. Madisch, et al., "Hydrogel-β-TCP scaffolds and stem cells for tissue engineering bone," Bone, vol. 38, pp. 555-563.
[21] I. W. Hamley, G. Cheng, and V. Castelletto, "A Thermoresponsive Hydrogel Based on Telechelic PEG End-Capped with Hydrophobic Dipeptides," Macromolecular Bioscience, vol. 11, pp. 1068-1078, 2011.
[22] N. Tzokova, C. M. Fernyhough, P. D. Topham, N. Sandon, D. J. Adams, M. F. Butler, et al., "Soft Hydrogels from Nanotubes of Poly(ethylene oxide)−Tetraphenylalanine Conjugates Prepared by Click Chemistry," Langmuir, vol. 25, pp. 2479-2485, 2009/02/17 2009.
[23] I. W. Hamley, "PEG–Peptide Conjugates," Biomacromolecules, vol. 15, pp. 1543-1559, 2014/05/12 2014.
[24] J. P. Gong, "Why are double network hydrogels so tough?," Soft Matter, vol. 6, pp. 2583-2590, 2010.
[25] M. A. Haque, T. Kurokawa, and J. P. Gong, "Super tough double network hydrogels and their application as biomaterials," Polymer, vol. 53, pp. 1805-1822, 2012/04/17/ 2012.
[26] Y. Xie, J. Zhao, R. Huang, W. Qi, Y. Wang, R. Su, et al., "Calcium-Ion-Triggered Co-assembly of Peptide and Polysaccharide into a Hybrid Hydrogel for Drug Delivery," Nanoscale Res Lett, vol. 11, p. 184, Dec 2016.
[27] Z. Liang, C. Liu, L. Li, P. Xu, G. Luo, M. Ding, et al., "Double-Network Hydrogel with Tunable Mechanical Performance and Biocompatibility for the Fabrication of Stem Cells-Encapsulated Fibers and 3D Assemble," vol. 6, p. 33462, 09/15/online 2016.
[28] "."
[29] T. Y. Cheng, M. H. Chen, W. H. Chang, M. Y. Huang, and T. W. Wang, "Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering," Biomaterials, vol. 34, 2013// 2013.
[30] Y. Li, J. Rodrigues, and H. Tomas, "Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications," Chemical Society Reviews, vol. 41, pp. 2193-2221, 2012.
[31] D. Seliktar, "Designing cell-compatible hydrogels for biomedical applications," Science, vol. 336, 2012// 2012.
[32] C. M. Scott, C. L. Forster, and E. Kokkoli, "Three-dimensional cell entrapment as a function of the weight percent of peptide-amphiphile hydrogels," Langmuir, vol. 31, 2015// 2015.
[33] G. Scott, S. Roy, Y. M. Abul-Haija, S. Fleming, S. Bai, and R. V. Ulijn, "Pickering stabilized peptide gel particles as tunable microenvironments for biocatalysis," Langmuir, vol. 29, pp. 14321-7, Nov 19 2013.
[34] D. M. Ryan, T. M. Doran, and B. L. Nilsson, "Complementary pi-pi interactions induce multicomponent coassembly into functional fibrils," Langmuir, vol. 27, pp. 11145-56, Sep 06 2011.
[35] S.-M. Hsu, F.-Y. Wu, T.-S. Lai, Y.-C. Lin, and H.-C. Lin, "Self-assembly and hydrogelation from multicomponent coassembly of pentafluorobenzyl-phenylalanine and pentafluorobenzyl-diphenylalanine," RSC Adv., vol. 5, pp. 22943-22946, 2015.
[36] W. Y. Su, Y. C. Chen, and F. H. Lin, "Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration," Acta Biomater, vol. 6, pp. 3044-55, Aug 2010.
[37] S.-M. Hsu, Y.-C. Lin, J.-W. Chang, Y.-H. Liu, and H.-C. Lin, "Intramolecular Interactions of a Phenyl/Perfluorophenyl Pair in the Formation of Supramolecular Nanofibers and Hydrogels," Angewandte Chemie International Edition, vol. 53, pp. 1921-1927, 2014.
[38] L. Pineiro, M. Novo, and W. Al-Soufi, "Fluorescence emission of pyrene in surfactant solutions," Adv Colloid Interface Sci, vol. 215, pp. 1-12, Jan 2015.
[39] L. H. Beun, I. M. Storm, M. W. Werten, F. A. de Wolf, M. A. Cohen Stuart, and R. de Vries, "From micelles to fibers: balancing self-assembling and random coiling domains in pH-responsive silk-collagen-like protein-based polymers," Biomacromolecules, vol. 15, pp. 3349-57, Sep 08 2014.
[40] K. Reichenbacher, H. I. Suss, and J. Hulliger, "Fluorine in crystal engineering--"the little atom that could"," Chem Soc Rev, vol. 34, pp. 22-30, Jan 2005.
[41] D. M. Ryan, S. B. Anderson, F. T. Senguen, R. E. Youngman, and B. L. Nilsson, "Self-assembly and hydrogelation promoted by F5-phenylalanine," Soft Matter, vol. 6, pp. 475-479, 2010.
[42] D. M. Ryan, S. B. Anderson, and B. L. Nilsson, "The influence of side-chain halogenation on the self-assembly and hydrogelation of Fmoc-phenylalanine derivatives," Soft Matter, vol. 6, p. 3220, 2010.
[43] F.-Y. Wu, S.-M. Hsu, H. Cheng, L.-H. Hsu, and H.-C. Lin, "The effect of fluorine on supramolecular hydrogelation of 4-fluorobenzyl-capped diphenylalanine," New Journal of Chemistry, vol. 39, pp. 4240-4243, 2015.
[44] D. M. Ryan, T. M. Doran, and B. L. Nilsson, "Stabilizing self-assembled Fmoc-F5-Phe hydrogels by co-assembly with PEG-functionalized monomers," Chemical Communications, vol. 47, pp. 475-477, 2011.
[45] F.-Q. An, M. Li, X.-D. Guo, H.-Y. Wang, R.-Y. Wu, T.-P. Hu, et al., "Selective adsorption of AuCl4− on chemically modified D301 resin with containing N/S functional polymer," Journal of Environmental Chemical Engineering, vol. 5, pp. 10-15, 2// 2017.
[46] W. Liyanage and B. L. Nilsson, "Substituent Effects on the Self-Assembly/Coassembly and Hydrogelation of Phenylalanine Derivatives," Langmuir, vol. 32, pp. 787-99, Jan 26 2016.
[47] E. C. Lee, B. H. Hong, J. Y. Lee, J. C. Kim, D. Kim, Y. Kim, et al., "Substituent Effects on the Edge-to-Face Aromatic Interactions," Journal of the American Chemical Society, vol. 127, pp. 4530-4537, 2005/03/01 2005.