糖胺聚醣複合水膠搭載聚電解複合奈米粒子應用於內源性幹細胞調控與中樞神經系統再生

簡易檢索 / 詳目顯示

回結果列表

研究生：	簡維宏 Jian, Wei-Hong
論文名稱：	糖胺聚醣複合水膠搭載聚電解複合奈米粒子應用於內源性幹細胞調控與中樞神經系統再生 Glycosaminoglycan-based Hybrid Hydrogel Encapsulated with Polyelectrolyte Complex Nanoparticles for Endogenous Stem Cell Regulation in Central Nervous System Regeneration
指導教授：	王子威 Wang, Tzu-Wei
口試委員:	吳錫苓洪士杰葉晨聖
學位類別：	碩士 Master
系所名稱：	工學院 - 材料科學工程學系 Materials Science and Engineering
論文出版年：	2017
畢業學年度：	106
語文別：	英文
論文頁數：	104
中文關鍵詞：	糖胺聚醣、聚電解奈米粒子、生長因子、神經幹細胞、水膠、腦
外文關鍵詞：	glycosaminoglycan, polyelectrolyte complex nanoparticle, growth factors, neural stem cell, hydrogel, brain
相關次數：	點閱：4 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

神經幹細胞(NSCs)具有修復中樞神經系統受損的能力，為腦創傷、腦中風及腦退化性神經疾病開創極具潛力的治療策略。然而，神經幹細胞在腦創傷部位的再生能力不佳，這是由於創傷部位極劇的發炎反應、失去結構性的支持、以及缺乏營養因子的滋養，而限制了治療效果。腦部正常的細胞外間質(ECM)由多種物質組成，例如透明質酸(HA)及蛋白聚醣(proteoglycan)等等，這些ECM的組成物提供了理想的微環境，使生長因子、趨化因子及其它生物活性因子擁有良好的儲存空間，以及避免蛋白質受到蛋白質分解酶的降解，並在生物體內提供了促進NSCs增生及分化的適當條件。因此，在本研究中，我們特別開發模仿ECM結構及組成的水膠，成份包含巨分子量的透明質酸以及糖胺聚醣(glycosaminoglycan)為基底製備的聚電解複合奈米粒子(PCNs)，可用來搭載基質細胞衍生因子(SDF-1α)和纖維母細胞生長因子（bFGF），同時藉由患部位置基質金屬蛋白酶(MMP)的活性影響，達到長效性控制釋放的效果。SDF-1α與硫酸乙酰肝素(heparan sulfate)以靜電作用力形成複合物有助於優化SDF-1α對其受體的表現，並且能夠在受傷區域吸引內源性的NSCs前來。除此之外， bFGF與硫酸軟骨素(chondroitin sulfate)形成複合體，能夠有效地調控內源性的NSCs增生及分化。而在生長因子的長效控制釋放方面，我們利用MMP可降解及MMP不可降解之多肽與PCN形成鍵結，隨後再與HA水膠交聯，由於多肽鏈受到MMP的降解能力不同，因此可達到不同階段性生長因子的釋放。此研究結合了搭載兩種生長因子的複合奈米粒子及模仿腦細胞外基質結構的水膠，不僅可進行局部注射，更可穩定生長因子於生理環境下的生物活性。更進一步地，水膠所釋放帶有生長因子的PCN不僅可促進內源性NSCs的化學趨向性(chemotactic recruitment)及存活率，並提供幹細胞理想的增生及分化環境，可望在腦神經組織的再生及修復上達到良好的效用。

Neural stem cells (NSCs) provide potential therapeutic strategy for central nervous system repair after traumatic injury, stroke and degenerative neural disease. However, poor regenerative capability of NSCs in the lesion site limits their therapeutic efficacy because of continuous inflammatory response, loss of structural support, and trophic factors deficiency, etc. Normal extracellular matrix (ECM) in the brain is organized by hyaluronic acid (HA) and proteoglycans, both of which provide an ideal microenvironment for binding, stabilization, and protection of growth factors, chemokines and other ECM proteins from degradation by proteinases. In this study, we specifically develop an ECM-mimetic hydrogel composed of high molecular weight HA and glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCNs) to deliver stromal cell-derived factor-1α (SDF-1α) and basic fibroblast growth factor (bFGF). SDF-1α bounded on heparan sulfate is known to optimize SDF-1α presentation and to recruit endogenous NSCs to the wound area. On the other hand, continuous expression of bFGF that is complexed with chondroitin sulfate plays a critical role in regulating injury-induced NSC proliferation and differentiation. To protect and controllably release the growth factors, the hybrid glycosaminoglycan-based biomatrix and MMP-cleavable peptides linked on the PCNs in hydrogel are tailor designed and developed to perform sustainable controlled release of growth factors in response to matrix metalloproteinase (MMP) activity by physiological requirement. We demonstrate that the combination of growth factor-loaded PCNs and glycosaminoglycan-based hydrogel can be locally injected and preserve bioactivity of the loaded growth factors. Specifically, delivery of SDF-1α and bFGF sequestered on PCNs can enhance chemotactic recruitment and survival of endogenous NSCs with stem cell niche to stimulate NSC proliferation for neural tissue repair and regeneration in the brain.

Abstract    II
摘要    III
Acknowledgement    IV
Table of Contents    i
Figure Index    v
Chapter 1. Introduction    1
1    Brain injuries    1
1.1    Statistics    1
1.2    Pathology    1
2    Challenges in current therapeutic strategies    3
2.1    Drug-based treatment    3
2.2    Cell-based treatment    4
3    Endogenous regenerative responses in CNS    5
3.1    Programming neurogenesis    5
3.2    Endogenous factors that regulate neural stem cells after brain injuries    6
4    Motivation and objective of this study    9
Chapter 2. Literature Review    13
1    Biomaterials to modify the post-injury environment    13
2    Molecular agents to modulate endogenous neural stem cell behavior    18
2.1    Promotion of NSC migration and recruitment    19
2.2    Enhancement of NSC proliferation    21
3    Strategies for molecular agent delivery    23
3.1    Hydrogel-based molecular agent delivery systems    23
3.2    Direct loading    24
3.3    Electrostatic sequestration with glycosaminoglycan    25
3.4    Nanohybrid hydrogel    29
Chapter 3. Theoretical Basis    31
1    Polyelectrolyte complex nanoparticles    31
2    Bioresponsive nanohybrid hydrogel    33
3    Regulation and acceleration of neural tissue regeneration    34
Chapter 4. Materials and Methods    35
1    Material list    35
2    Experimental design    36
3    Synthesis and physiochemical characterization of PCN    36
3.1    Maleimide group conjugation on chondroitin sulfate and heparan sulfate    36
3.2    bFGF mCSPCN and SDF-1α mHSPCN synthesis    37
3.3    Characterization of PCNs    39
3.4    Growth factor loading efficiency    39
4    Formation and characterization of nanohybrid hydrogel    39
4.1    Synthesis and characterization of aldehyde-functionalized HA    39
4.2    PCN-HA nanohybrid hydrogel formation    40
4.3    Microscopic morphology and mechanical properties of hydrogel    40
4.4    In vitro degradation behavior of hydrogel    41
4.5    Growth factor and PCN release behavior from hydrogel    42
5    In vitro study    43
5.1    Culture of neural stem cells    43
5.2    Encapsulation of NSCs in nanohybrid hydrogels    43
5.3    Biocompatibility assessment    43
5.4    Growth factor protection by PCN    44
5.5    Proliferation assessment    45
5.6    Cylindrical hydrogel construct for NSC recruitment    45
6    In vivo study    46
6.1    Design of animal experiment    46
6.2    Photothrombotic ischemia (PTI) model and gel implantation    48
6.3    Magnetic resonance imaging (MRI) and analysis    50
6.4    Behavioral measurement    50
6.5    Tissue processing and immunohistochemistry (IHC)    51
7    Statistical analysis    52
Chapter 5. Results    53
1    Characterization of maleimide modification on GAGs    53
2    Physiochemical characterization of PCN    55
3    Characterization of nanohybrid hydrogel    57
3.1    Characterization of HA-ALD polymers    57
3.2    Morphology of ECM-mimetic hydrogel matrices    59
3.3    Rheological properties of nanohybrid hydrogel    60
3.4    Degradation and PCN release kinetics of nanohybrid hydrogel    62
3.5    Release kinetics of bFGF and SDF-1α    64
3.6    MMP-mediated release    65
4    In vitro study    67
4.1    Cytocompatibility of nanohybrid hydrogel    67
4.2    Growth factor protection by PCN    68
4.3    NSC proliferation induced by bFGF expression in hydrogel    69
4.4    Chemotactic migration of NSCs induced by SDF-1α    71
5    In vivo study    74
5.1    Photothrombotic ischemia stroke in rat model    74
5.2    In vivo monitoring of stroke cavity after treatment    76
5.3    Motor recovery    78
5.4    Endogenous neurogenesis in brain tissue    79
Chapter 6. Discussion    87
1    Physicochemical properties of nanohybrid hydrogel    87
1.1    Physiochemical properties of PCNs and nanohybrid hydrogels    87
1.2    Stimulus-controlled delivery of bFGF and SDF-1α    88
2    Controlled signaling regulation of NSCs    89
3    Neuroregeneration in photothrombotic ischemia stroke    91
3.1    Ischemia stroke following photothrombotic insult    91
3.2    Neuroregeneration after treatments    92
Chapter 7. Conclusion    94
References    96

                                

1. C. P. Addington, A. Roussas, D. Dutta, S. E. Stabenfeldt, Endogenous Repair Signaling after Brain Injury and Complementary Bioengineering Approaches to Enhance Neural Regeneration. Biomarker Insights 10, (2015).
2. H. M. Bramlett, W. D. Dietrich, Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences. Journal of Cerebral Blood Flow & Metabolism 24, 133-150 (2004).
3. R. L. Sacco, S. E. Kasner, J. P. Broderick, L. R. Caplan, J. J. Connors, A. Culebras, M. S. V. Elkind, M. G. George, A. D. Hamdan, R. T. Higashida, B. L. Hoh, L. S. Janis, C. S. Kase, D. O. Kleindorfer, J.-M. Lee, M. E. Moseley, E. D. Peterson, T. N. Turan, A. L. Valderrama, H. V. Vinters, An Updated Definition of Stroke for the 21st Century. A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association 44, 2064-2089 (2013).
4. S. D. Smith, C. J. Eskey, Hemorrhagic Stroke. Radiologic Clinics of North America 49, 27-45 (2011).
5. T. M. Woodruff, J. Thundyil, S.-C. Tang, C. G. Sobey, S. M. Taylor, T. V. Arumugam, Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Molecular Neurodegeneration 6, 11-29 (2011).
6. M. W. Greve, B. J. Zink, Pathophysiology of traumatic brain injury. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 76, 97-104 (2009).
7. M. Prins, T. Greco, D. Alexander, C. C. Giza, The pathophysiology of traumatic brain injury at a glance. Disease Models & Mechanisms 6, 1307-1315 (2013).
8. S. Ding, Ca(2+) Signaling in Astrocytes and its Role in Ischemic Stroke. Advances in neurobiology 11, 189-211 (2014).
9. B. Bartnik-Olson, N. Harris, K. Shijo, R. Sutton, Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy. Frontiers in Neuroenergetics 5, (2013).
10. J. C. Hemphill, P. Andrews, M. De Georgia, Multimodal monitoring and neurocritical care bioinformatics. Nat Rev Neurol 7, 451-460 (2011).
11. J. M. Ziebell, M. C. Morganti-Kossmann, Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury. Neurotherapeutics 7, 22-30 (2010).
12. D. J. Loane, A. I. Faden, Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol. Sci. 31, 596-604 (2010).
13. K. C. Rossi, J. W. Liang, N. Wilson, S. Tuhrim, M. S. Dhamoon, More Time Is Taken to Administer Tissue Plasminogen Activator in Ischemic Stroke Patients with Earlier Presentations. Journal of Stroke and Cerebrovascular Diseases 26, 70-73 (2017).
14. G. A. Donnan, S. M. Davis, M. W. Parsons, H. Ma, H. M. Dewey, D. W. Howells, How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol 7, 400-409 (2011).
15. R. Y. Tam, T. Fuehrmann, N. Mitrousis, M. S. Shoichet, Regenerative therapies for central nervous system diseases: a biomaterials approach. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39, 169-188 (2014).
16. Z. Kokaia, G. Martino, M. Schwartz, O. Lindvall, Cross-talk between neural stem cells and immune cells: the key to better brain repair[quest]. Nat Neurosci 15, 1078-1087 (2012).
17. D. Sun, The potential of neural transplantation for brain repair and regeneration following traumatic brain injury. Neural Regeneration Research 11, 18-22 (2016).
18. P. Dibajnia, C. M. Morshead, Role of neural precursor cells in promoting repair following stroke. Acta Pharmacol. Sin. 34, 78-90 (2013).
19. C.-A. Grégoire, B. L. Goldenstein, E. M. Floriddia, F. Barnabé-Heider, K. J. L. Fernandes, Endogenous neural stem cell responses to stroke and spinal cord injury. Glia 63, 1469-1482 (2015).
20. N. Picard‐Riera, B. Nait‐Oumesmar, A. B. V. Evercooren, Endogenous adult neural stem cells: Limits and potential to repair the injured central nervous system. Journal of Neuroscience Research 76, 223-231 (2004).
21. G. J. Sun, Y. Zhou, R. P. Stadel, J. Moss, J. H. A. Yong, S. Ito, N. K. Kawasaki, A. T. Phan, J. H. Oh, N. Modak, R. R. Reed, N. Toni, H. Song, G.-l. Ming, Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain. Proc. Natl Acad. Sci. USA 112, 9484-9489 (2015).
22. M. Sawada, M. Matsumoto, K. Sawamoto, Vascular regulation of adult neurogenesis under physiological and pathological conditions. Frontiers in Neuroscience 8, (2014).
23. T. Kojima, Y. Hirota, M. Ema, S. Takahashi, I. Miyoshi, H. Okano, K. Sawamoto, Subventricular Zone-Derived Neural Progenitor Cells Migrate Along a Blood Vessel Scaffold Toward The Post-stroke Striatum. STEM CELLS 28, 545-554 (2010).
24. J. Imitola, K. Raddassi, K. I. Park, F. J. Mueller, M. Nieto, Y. D. Teng, D. Frenkel, J. Li, R. L. Sidman, C. A. Walsh, E. Y. Snyder, S. J. Khoury, Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc. Natl Acad. Sci. USA 101, 18117-18122 (2004).
25. M. Rabenstein, J. Hucklenbroich, A. Willuweit, A. Ladwig, G. R. Fink, M. Schroeter, K.-J. Langen, M. A. Rueger, Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4. Stem Cell Research & Therapy 6, 99-110 (2015).
26. H. X. Chu, T. V. Arumugam, M. Gelderblom, T. Magnus, G. R. Drummond, C. G. Sobey, Role of CCR2 in Inflammatory Conditions of the Central Nervous System. Journal of Cerebral Blood Flow & Metabolism 34, 1425-1429 (2014).
27. A. Guyon, CXCL12 chemokine and its receptors as major players in the interactions between immune and nervous systems. Frontiers in Cellular Neuroscience 8, (2014).
28. D. Alagappan, D. A. Lazzarino, R. J. Felling, M. Balan, S. V. Kotenko, S. W. Levison, Brain Injury Expands the Numbers of Neural Stem Cells and Progenitors in the SVZ by Enhancing Their Responsiveness to EGF. ASN Neuro 1, (2009).
29. S. A. Frautschy, P. A. Walicke, A. Baird, Localization of basic fibroblast growth factor and its mRNA after CNS injury. Brain Research 553, 291-299 (1991).
30. I. Kiprianova, K. Schindowski, O. von Bohlen und Halbach, S. Krause, R. Dono, M. Schwaninger, K. Unsicker, Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2. Exp. Neurol. 189, 252-260 (2004).
31. S. Yoshimura, Y. Takagi, J. Harada, T. Teramoto, S. S. Thomas, C. Waeber, J. C. Bakowska, X. O. Breakefield, M. A. Moskowitz, FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc. Natl Acad. Sci. USA 98, 5874-5879 (2001).
32. O. Thau-Zuchman, E. Shohami, A. G. Alexandrovich, R. R. Leker, Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 30, 1008-1016 (2010).
33. T. R. M. Filippo, L. T. Galindo, G. F. Barnabe, C. B. Ariza, L. E. Mello, M. A. Juliano, L. Juliano, M. A. Porcionatto, CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells. Stem cell research 11, 913-925 (2013).
34. S. Gyoneva, R. M. Ransohoff, Inflammatory reaction after traumatic brain injury: therapeutic potential of targeting cell–cell comunication by chemokines. Trends Pharmacol. Sci. 36, 471-480 (2015).
35. D. Michalski, W. Härtig, M. Krueger, C. Hobohm, J. A. Käs, T. Fuhs, A novel approach for mechanical tissue characterization indicates decreased elastic strength in brain areas affected by experimental thromboembolic stroke. Neuroreport 26, 583-587 (2015).
36. L. R. Nih, S. T. Carmichael, T. Segura, Hydrogels for brain repair after stroke: an emerging treatment option. Curr. Opin. Biotechnol. 40, 155-163 (2016).
37. G. T. Fallenstein, V. D. Hulce, J. W. Melvin, Dynamic mechanical properties of human brain tissue. J. Biomech. 2, 217-226 (1969).
38. E. Ruoslahti, Brain extracellular matrix. Glycobiology 6, 489-492 (1996).
39. J. K. Mouw, G. Ou, V. M. Weaver, Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 15, 771-785 (2014).
40. L. S. Sherman, S. Matsumoto, W. Su, T. Srivastava, S. A. Back, Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases. International Journal of Cell Biology 2015, 10-19 (2015).
41. J. Zhong, A. Chan, L. Morad, H. I. Kornblum, F. Guoping, S. T. Carmichael, Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke. Neurorehabilitation and Neural Repair 24, 636-644 (2010).
42. J. Struve, P. C. Maher, Y.-q. Li, S. Kinney, M. G. Fehlings, C. Kuntz, L. S. Sherman, Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation. Glia 52, 16-24 (2005).
43. M. A. K. a. T. G. Malgorzata Litwiniuk, PhD Hyaluronic Acid in Inflammation and Tissue Regeneration. Wounds 28, 78-88 (2016).
44. Y. Wang, M. J. Cooke, N. Sachewsky, C. M. Morshead, M. S. Shoichet, Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke. J. Controlled Release 172, 1-11 (2013).
45. A. Tuladhar, C. M. Morshead, M. S. Shoichet, Circumventing the blood–brain barrier: Local delivery of cyclosporin A stimulates stem cells in stroke-injured rat brain. J. Controlled Release 215, 1-11 (2015).
46. J. Zhong, A. Chan, L. Morad, H. I. Kornblum, G. Fan, S. T. Carmichael, Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke. Neurorehabilitation and Neural Repair 24, 636-644 (2010).
47. H. Okano, K. Sawamoto, Neural stem cells: involvement in adult neurogenesis and CNS repair. Philosophical Transactions of the Royal Society B: Biological Sciences 363, 2111-2122 (2008).
48. D. Lozano, G. S. Gonzales-Portillo, S. Acosta, I. de la Pena, N. Tajiri, Y. Kaneko, C. V. Borlongan, Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatric disease and treatment 11, 97-106 (2015).
49. S. Lanfranconi, F. Locatelli, S. Corti, L. Candelise, G. P. Comi, P. L. Baron, S. Strazzer, N. Bresolin, A. Bersano, Growth factors in ischemic stroke. J. Cell. Mol. Med. 15, 1645-1687 (2011).
50. C. P. Addington, C. M. Pauken, M. R. Caplan, S. E. Stabenfeldt, The role of SDF-1alpha-ECM crosstalk in determining neural stem cell fate. Biomaterials 35, 3263-3272 (2014).
51. L. N. Zamproni, M. V. Mundim, M. A. Porcionatto, A. des Rieux, Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment. International Journal of Pharmaceutics 519, 323-331 (2017).
52. D. H. Kim, Y. K. Seo, T. Thambi, G. J. Moon, J. P. Son, G. Li, J. H. Park, J. H. Lee, H. H. Kim, D. S. Lee, O. Y. Bang, Enhancing neurogenesis and angiogenesis with target delivery of stromal cell derived factor-1α using a dual ionic pH-sensitive copolymer. Biomaterials 61, 115-125 (2015).
53. K. Wada, H. Sugimori, P. G. Bhide, M. A. Moskowitz, S. P. Finklestein, Effect of basic fibroblast growth factor treatment on brain progenitor cells after permanent focal ischemia in rats. Stroke 34, 2722-2728 (2003).
54. T. Kawamata, W. D. Dietrich, T. Schallert, J. E. Gotts, R. R. Cocke, L. I. Benowitz, S. P. Finklestein, Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. Proc. Natl Acad. Sci. USA 94, 8179-8184 (1997).
55. B.-W. Song, H. V. Vinters, D. Wu, W. M. Pardridge, Enhanced Neuroprotective Effects of Basic Fibroblast Growth Factor in Regional Brain Ischemia after Conjugation to a Blood-Brain Barrier Delivery Vector. Journal of Pharmacology and Experimental Therapeutics 301, 605-610 (2002).
56. U. Galderisi, G. Peluso, G. Di Bernardo, A. Calarco, M. D'Apolito, O. Petillo, M. Cipollaro, F. R. Fusco, M. A. Melone, Efficient cultivation of neural stem cells with controlled delivery of FGF-2. Stem cell research 10, 85-94 (2013).
57. A. K. A. Silva, C. Richard, M. Bessodes, D. Scherman, O.-W. Merten, Growth Factor Delivery Approaches in Hydrogels. Biomacromolecules 10, 9-18 (2009).
58. Z. Z. Khaing, R. C. Thomas, S. A. Geissler, C. E. Schmidt, Advanced biomaterials for repairing the nervous system: what can hydrogels do for the brain? Materials Today 17, 332-340 (2014).
59. L. Liu, Y. Liu, J. Li, G. Du, J. Chen, Microbial production of hyaluronic acid: current state, challenges, and perspectives. Microbial Cell Factories 10, 99-107 (2011).
60. K. Xue, M. J. Webber, R. S. Langer, D. G. Anderson, Shear-thinning hyaluronic acid hydrogels for insulin delivery. Frontiers in Bioengineering and Biotechnology.
61. S. Zhu, L. Nih, S. T. Carmichael, Y. Lu, T. Segura, Enzyme-Responsive Delivery of Multiple Proteins with Spatiotemporal Control. Adv. Mater. 27, 3620-3625 (2015).
62. L. Macri, D. Silverstein, R. A. Clark, Growth factor binding to the pericellular matrix and its importance in tissue engineering. Advanced drug delivery reviews 59, 1366-1381 (2007).
63. A. D. DiGabriele, I. Lax, D. I. Chen, C. M. Svahn, M. Jaye, J. Schlessinger, W. A. Hendrickson, Structure of a heparin-linked biologically active dimer of fibroblast growth factor. Nature 393, 812-817 (1998).
64. G. Bhakta, B. Rai, Z. X. H. Lim, J. H. Hui, G. S. Stein, A. J. van Wijnen, V. Nurcombe, G. D. Prestwich, S. M. Cool, Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2. Biomaterials 33, 6113-6122 (2012).
65. Q. Feng, S. Lin, K. Zhang, C. Dong, T. Wu, H. Huang, X. Yan, L. Zhang, G. Li, L. Bian, Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. Acta Biomater. 53, 329-342 (2017).
66. L. Karumbaiah, S. F. Enam, A. C. Brown, T. Saxena, M. I. Betancur, T. H. Barker, R. V. Bellamkonda, Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells. Bioconjugate Chemistry 26, 2336-2349 (2015).
67. A. Hasan, A. Khattab, M. A. Islam, K. A. Hweij, J. Zeitouny, R. Waters, M. Sayegh, M. M. Hossain, A. Paul, Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction. Advanced Science 2, 1500122 (2015).
68. P. Thoniyot, M. J. Tan, A. A. Karim, D. J. Young, X. J. Loh, Nanoparticle–Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi-Functional Materials. Advanced Science 2, 1400010 (2015).
69. H. Tan, Q. Shen, X. Jia, Z. Yuan, D. Xiong, Injectable Nanohybrid Scaffold for Biopharmaceuticals Delivery and Soft Tissue Engineering. Macromolecular Rapid Communications 33, 2015-2022 (2012).
70. T. C. Lim, S. Rokkappanavar, W. S. Toh, L. S. Wang, M. Kurisawa, M. Spector, Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1alpha release and compatible structural support. FASEB J. 27, 1023-1033 (2013).
71. E. A. Appel, M. W. Tibbitt, M. J. Webber, B. A. Mattix, O. Veiseh, R. Langer, Self-assembled hydrogels utilizing polymer-nanoparticle interactions. Nature communications 6, 6295-6313 (2015).
72. L. W. Place, M. Sekyi, M. J. Kipper, Aggrecan-mimetic, glycosaminoglycan-containing nanoparticles for growth factor stabilization and delivery. Biomacromolecules 15, 680-689 (2014).
73. Y.-C. Huang, T.-J. Liu, Mobilization of mesenchymal stem cells by stromal cell-derived factor-1 released from chitosan/tripolyphosphate/fucoidan nanoparticles. Acta Biomater. 8, 1048-1056 (2012).
74. S. Boddohi, M. J. Kipper, Engineering Nanoassemblies of Polysaccharides. Adv. Mater. 22, 2998-3016 (2010).
75. T. Netelenbos, S. Zuijderduijn, J. V. D. Born, F. L. Kessler, S. Zweegman, P. C. Huijgens, A. M. Dräger, Proteoglycans guide SDF-1-induced migration of hematopoietic progenitor cells. J. Leukoc. Biol. 72, 353-362 (2002).
76. S. Sirko, A. von Holst, A. Weber, A. Wizenmann, U. Theocharidis, M. Götz, A. Faissner, Chondroitin Sulfates Are Required for Fibroblast Growth Factor-2-Dependent Proliferation and Maintenance in Neural Stem Cells and for Epidermal Growth Factor-Dependent Migration of Their Progeny. STEM CELLS 28, 775-787 (2010).
77. E. Migliorini, D. Thakar, J. Kühnle, R. Sadir, D. P. Dyer, Y. Li, C. Sun, B. F. Volkman, T. M. Handel, L. Coche-Guerente, D. G. Fernig, H. Lortat-Jacob, R. P. Richter, Cytokines and growth factors cross-link heparan sulfate. Open Biology 5, 150046 (2015).
78. C. T. Veldkamp, F. C. Peterson, A. J. Pelzek, B. F. Volkman, The monomer–dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is altered by pH, phosphate, sulfate, and heparin. Protein Science 14, 1071-1081 (2005).
79. S. Sirko, A. von Holst, A. Wizenmann, M. Götz, A. Faissner, Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134, 2727-2738 (2007).
80. J. A. Burdick, W. L. Murphy, Moving from static to dynamic complexity in hydrogel design. Nature communications 3, 1269 (2012).
81. M. Sifringer, V. Stefovska, I. Zentner, B. Hansen, A. Stepulak, C. Knaute, J. Marzahn, C. Ikonomidou, The role of matrix metalloproteinases in infant traumatic brain injury. Neurobiol. Dis. 25, 526-535 (2007).
82. M. Grossetete, J. Phelps, L. Arko, H. Yonas, G. A. Rosenberg, Elevation of MMP-3 and MMP-9 in CSF and Blood in Patients with Severe Traumatic Brain Injury. Neurosurgery 65, 702-708 (2009).
83. S. Khetan, M. Guvendiren, W. R. Legant, D. M. Cohen, C. S. Chen, J. A. Burdick, Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458-465 (2013).
84. B. P. Purcell, D. Lobb, M. B. Charati, S. M. Dorsey, R. J. Wade, K. N. Zellars, H. Doviak, S. Pettaway, C. B. Logdon, J. A. Shuman, P. D. Freels, J. H. Gorman, 3rd, R. C. Gorman, F. G. Spinale, J. A. Burdick, Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat. Mater. 13, 653-661 (2014).
85. Y. C. Chen, W. Y. Su, S. H. Yang, A. Gefen, F. H. Lin, In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration. Acta Biomater. 9, 5181-5193 (2013).
86. N. Oueslati, P. Leblanc, C. Harscoat-Schiavo, E. Rondags, S. Meunier, R. Kapel, I. Marc, CTAB turbidimetric method for assaying hyaluronic acid in complex environments and under cross-linked form. Carbohydr. Polym. 112, 102-108 (2014).
87. Y. Ge, Y. Zhang, S. He, F. Nie, G. Teng, N. Gu, Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging. Nanoscale Res. Lett. 4, 287-295 (2009).
88. J. Zhong, A. Chan, L. Morad, H. I. Kornblum, G. Fan, S. T. Carmichael, Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke. Neurorehabil. Neural. Repair 24, 636-644 (2010).
89. T.-N. Lin, S.-W. Sun, W.-M. Cheung, F. Li, C. Chang, Dynamic Changes in Cerebral Blood Flow and Angiogenesis After Transient Focal Cerebral Ischemia in Rats. Stroke 33, 2985-2991 (2002).
90. K. Vulic, M. S. Shoichet, Tunable Growth Factor Delivery from Injectable Hydrogels for Tissue Engineering. JACS 134, 882-885 (2012).
91. J. G. Hardy, P. Lin, C. E. Schmidt, Biodegradable hydrogels composed of oxime crosslinked poly(ethylene glycol), hyaluronic acid and collagen: a tunable platform for soft tissue engineering. J. Biomater. Sci., Polym. Ed. 26, 143-161 (2015).
92. J. W. Murphy, Y. Cho, A. Sachpatzidis, C. Fan, M. E. Hodsdon, E. Lolis, Structural and functional basis of CXCL12 (stromal cell-derived factor-1 alpha) binding to heparin. J. Biol. Chem. 282, 10018-10027 (2007).
93. S. Lotz, S. Goderie, N. Tokas, S. E. Hirsch, F. Ahmad, B. Corneo, S. Le, A. Banerjee, R. S. Kane, J. H. Stern, S. Temple, C. A. Fasano, Sustained Levels of FGF2 Maintain Undifferentiated Stem Cell Cultures with Biweekly Feeding. PLOS ONE 8, e56289 (2013).
94. U. Freudenberg, Y. Liang, K. L. Kiick, C. Werner, Glycosaminoglycan-Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials. Adv. Mater. 28, 8861-8891 (2016).
95. H. Li, N. Zhang, H.-Y. Lin, Y. Yu, Q.-Y. Cai, L. Ma, S. Ding, Histological, cellular and behavioral assessments of stroke outcomes after photothrombosis-induced ischemia in adult mice. BMC Neuroscience 15, 58 (2014).
96. U. I. Tuor, Q. Deng, D. Rushforth, T. Foniok, M. Qiao, Model of minor stroke with mild peri-infarct ischemic injury. Journal of Neuroscience Methods 268, 56-65 (2016).
97. J. E. Burda, A. M. Bernstein, M. V. Sofroniew, Astrocyte roles in traumatic brain injury. Exp. Neurol. 275, 305-315 (2016).
98. K. C. Spencer, J. C. Sy, K. B. Ramadi, A. M. Graybiel, R. Langer, M. J. Cima, Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants. Sci. Rep. 7, 1952 (2017).
99. Y. Li, J. Huang, X. He, G. Tang, Y. H. Tang, Y. Liu, X. Lin, Y. Lu, G. Y. Yang, Y. Wang, Postacute stromal cell-derived factor-1alpha expression promotes neurovascular recovery in ischemic mice. Stroke 45, 1822-1829 (2014).

簡易檢索 / 詳目顯示

相關論文