臺灣博碩士論文加值系統

PART-1
本實驗研究氧化石墨烯衍生物（ graphene oxide, GO ）結合物理性金奈米粒子（ gold nanoparticle, AuNP ）促進間葉幹細（ mesenchymal stem cells, MSC ）移動、增生及分化。氧化石墨烯衍生物（graphene oxide, GO）對於生物體不具毒性、製作成本低、機械性質高、熱性能佳且具有良好的導電性、電阻率低可應用於生物感測器中的晶體，甚至誘導幹細胞分化為神經元細胞，骨細胞，脂肪細胞的能力，使得氧化石墨烯衍生物成為生物醫學應用中成為被廣泛應用的材料。物理性金奈米粒子（ gold nanoparticle, AuNP ）能促進間葉幹細胞生長、降低血小板活化程度且減少活性氧化物質的產生。本研究將探討石墨烯衍生物結合奈米金粒子用於組織工程應用的潛力。將評估氧化石墨烯衍生物的生物相容性、生物功能及材料對細胞的分化能力。實驗中測試材料對細胞毒性反應、細胞貼附於材料上能力、細胞分化為成骨細胞及脂肪細胞的潛力。此外，我們將改變奈米金粒子的濃度高低與氧化石墨烯衍生物表面結合測試是否會去影響間葉幹細胞生長及爬行能力並研究對幹細胞分化的影響。從實驗中得知氧化石墨烯結合物理性奈米金粒子可促進間葉幹細胞（ MSC ）的爬行能力（ migration ability ）、在細胞週期（ Cell cycle ）中可以促進細胞增生及減少細胞凋亡，並且可以促進分化為神經、內皮、成骨、脂肪能力都能有效提升。
PART-2
本研究探討奈米金粒子 （gold nanoparticle） 結合基質細胞衍生因子-1α （stromal-cell derived factor-1α） 促進間葉幹細胞 （mesenchymal stem cells） 生長。再生醫療可分為幹細胞治療和奈米組織工程兩部分。幹細胞治療是使用幹細胞去修復損傷的組織，第一種，自體移植幹細胞在體外大量培養，再將幹細胞注射到病患受損組織，目標性的到達受損的組織使細胞自體修復，第二種，奈米組織工程是利用良好生物相容性及無毒性，可自我降解的生物材料，結合幹細胞達到修復組織的效用。而本篇研究所選擇材料為：基質細胞衍生因子1α （SDF-1α） ，稱為CXCL12，從受傷的細胞上接收信息，而基質細胞衍生因子1α結合到細胞膜上的CXCR4受體，並產生可修復的細胞增殖和遷移的修復信息。為了順利將 SDF-1α/CXCL12 通過細胞膜到達受損細胞中，我們在物理性奈米粒子與膠原蛋白交聯的同時與SDF-1α （Au-Col-SDF-1α） 結合，作為本研究的模型系統。我們測試細胞增殖以及細胞遷移能力。還測定了活性氧 （ROS） 生成能力的生物功能，隨後通過金屬蛋白?卅? （MMP） 檢測。觀察了Au-Col-SDF-1α奈米載體的生物相容性，生物功能及細胞分化能力。此外，基質細胞衍生因子-1α （SDF-1α） 表達的測定隨著基質細胞衍生因子1α （SDF-1α） 增加免疫吸附 （ELISA） 。而新型的幹細胞治療相結合的 Au-Col-SDF-1α 奈米載體複合基材可提供組織再生應用。

PART-1
The unique potential of graphene and its derivatives, such as graphene oxides (GOs), have made them one of the most promising materials for many biomedical applications, ranging from the delivery of drugs and genes to biosensing and even for the differentiation capacity of stem cells. Recent studies have also demonstrated that the graphene-nanoparticle hybrid materials offer addition advantageous functions for applications when compared to the use of either material alone. In the study, we propose to evaluate the potential of nanogold particle-decorated graphene derivatives for use in tissue engineering application. The biocompatibility ability and biological performance, such as cell growth, adhesion, differentiation and migration ability, will be evaluated in this study. Further, we will control the concentration of nanogold particles on GO surfaces and study its effects on the stem cells differentiation. Moreover, because graphene and GOs interact differently with the human mesenchymal stem cells (MSC). We suggest that the results of this research will apply effective clinical strategies for further disease treatments in the near future.
PART-2
Regenerative medicine can be divided into two parts: stem cell therapy and tissue engineering. Stem cell therapy is to use stem cells in repairing the injured tissue, like a house made biocompatible, self-degradable biomaterial, houses and escorts stem cells to its target . Upon stromal cell-derived factor-1α (SDF-1α) , known as CXCL12, receiving the message from injured cells , it combines to their membrane receptor CXCR4 and generates repair message for repairable cell proliferation and migration. To introduce therapeutic stem cell into injured cells by SDF-1α/CXCL12, we conjugated gold nanoparticles (AuNP) with SDF-1α (AuNP-SDF-1α) while cross-linked with collagen, as a model system in this study.We use to Dynamic Light Scattering (DLS) to identify the particle size, and in test cell proliferation as well as cell migration ability. It was also determined the biocompatibility at reactive oxygen species (ROS) generation ability and subsequently observed the biological performance of AuNP-SDF-1α nanocarrier by using metalloproteinase zymography (MMP) assay. Moreover, the determination of stromal cell-derived factor-1α (SDF-1α) expression was accompanied by Enzyme-linked immunosorbent (ELISA) assay. This novel AuNP-SDF-1α nanocarrier which combine with stem cell therapy may offer an approach for tissue regeneration application.

第一部分 I
致謝 II
中文摘要 III
英文摘要 IV
目錄 V
圖目錄 VII
表目錄 VIII
英文縮寫表 IX
第一章 前言 1
第一節 緒論 1
第二節 研究背景 2
一、 組織工程發展及應用 2
二、 奈米科技發展與應用 3
三、 奈米金粒子特性及應用 5
四、 氧化石墨烯介紹及應用 7
五、 間葉幹細胞 9
六、 氧化石磨烯在生醫材料與組織工程的應用 11
第三節 研究動機及目的 12
第二章 研究方法 13
第一節 實驗材料 13
第二節 實驗方法 20
第三章 研究結果 32
第四章 討論 42
第五章 結論 46
參考文獻 47



第二部分 95
中文摘要 96
英文摘要 97
目錄 98
圖目錄 99
英文縮寫表 100
第一章前言 101
第一節緒論 101
第二節研究背景 103
一、 幹細胞生長之微環境 103
二、 間葉幹細胞 105
三、 奈米金粒子特性及應用 107
四、 膠原蛋白的特性及應用 109
五、 基質細胞衍生因子-1 α 介紹 110
第三節研究動機及目的 111
第二章研究方法 112
第一節實驗材料 112
第二節實驗方法 119
第三節統計方法 139
第三章研究結果 140
第四章討論 155
第五章結論 161
參考文獻 162

PART-1
1.Shrivastava, S. and D. Dash, Applying nanotechnology to human health: revolution in biomedical sciences. Journal of Nanotechnology, 2009. 2009.
2.Chen, Z.-Y., et al., New development and application of ultrasound targeted microbubble destruction in gene therapy and drug delivery. Current gene therapy, 2013. 13(4): p. 250-274.
3.Lorden, E.R., H.M. Levinson, and K.W. Leong, Integration of drug, protein, and gene delivery systems with regenerative medicine. Drug delivery and translational research, 2015. 5(2): p. 168-186.
4.Chaturvedi, S., P.N. Dave, and N. Shah, Applications of nano-catalyst in new era. Journal of Saudi Chemical Society, 2012. 16(3): p. 307-325.
5.Martin, I., D. Wendt, and M. Heberer, The role of bioreactors in tissue engineering. TRENDS in Biotechnology, 2004. 22(2): p. 80-86.
6.Li, W.J., et al., Electrospun nanofibrous structure: a novel scaffold for tissue engineering. Journal of Biomedical Materials Research Part A, 2002. 60(4): p. 613-621.
7.Coquelin, A.W. and R.A. Gorski, Neuroendocrine control, stress, and immunity. Marcel Dekker, New York, 1984: p. 27-40.
8.Goenka, S., V. Sant, and S. Sant, Graphene-based nanomaterials for drug delivery and tissue engineering. Journal of Controlled Release, 2014. 173: p. 75-88.
9.Lee, W.C., et al., Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS nano, 2011. 5(9): p. 7334-7341.
10.Hung, H.-S., et al., Biocompatibility and favorable response of mesenchymal stem cells on fibronectin-gold nanocomposites. PloS one, 2013. 8(6): p. e65738.
11.Hung, H.-S., et al., In vitro study of a novel nanogold-collagen composite to enhance the mesenchymal stem cell behavior for vascular regeneration. PloS one, 2014. 9(8): p. e104019.
12.Yang, S., et al., The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue engineering, 2002. 8(1): p. 1-11.
13.Ma, Z., et al., Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue engineering, 2005. 11(1-2): p. 101-109.
14.Taniguchi, N. On the basic concept of nano-technology. in Proc. Intl. Conf. Prod. London, 1974. 1974. British Society of Precision Engineering.
15.Yang, Y., et al., Graphene based materials for biomedical applications. Materials Today, 2013. 16(10): p. 365-373.
16.Arora, P., et al., Nano?鬳egenerative medicine towards clinical outcome of stem cell and tissue engineering in humans. Journal of cellular and molecular medicine, 2012. 16(9): p. 1991-2000.
17.Calin, M., D. Stan, and V. Simion, Stem cell regenerative potential combined with nanotechnology and tissue engineering for myocardial regeneration. Current stem cell research & therapy, 2013. 8(4): p. 292-303.
18.Mohamed, A. and M.M. Xing, Nanomaterials and nanotechnology for skin tissue engineering. International journal of burns and trauma, 2012. 2(1): p. 29.
19.Tran, P.A., L. Zhang, and T.J. Webster, Carbon nanofibers and carbon nanotubes in regenerative medicine. Advanced drug delivery reviews, 2009. 61(12): p. 1097-1114.
20.Sheng, Z., et al., Protein-assisted fabrication of nano-reduced graphene oxide for combined in vivo photoacoustic imaging and photothermal therapy. Biomaterials, 2013. 34(21): p. 5236-5243.
21.Gholipourmalekabadi, M., et al., Targeted drug delivery based on gold nanoparticle derivatives. Current pharmaceutical design, 2017.
22.Kim, C.K., et al., Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. Journal of the American Chemical Society, 2009. 131(4): p. 1360-1361.
23.C Nagarwal, R., et al., Nanocrystal technology in the delivery of poorly soluble drugs: an overview. Current drug delivery, 2011. 8(4): p. 398-406.
24.Hsieh, S.-C., et al., Prominent Vascularization Capacity of Mesenchymal Stem Cells in Collagen–Gold Nanocomposites. ACS applied materials & interfaces, 2016. 8(42): p. 28982-29000.
25.Hung, H.-S., et al., Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites. Biomaterials, 2014. 35(25): p. 6810-6821.
26.Avolio, E., M. Caputo, and P. Madeddu, Stem cell therapy and tissue engineering for correction of congenital heart disease. Frontiers in cell and developmental biology, 2015. 3.
27.Huang, H., S. Hsu, and S.-h. Hsu, Current advances of stem cell-based approaches to tissue-engineered vascular grafts. OA Tissue Engineering, 2013. 1(1).
28.Lutz, J.-F., et al., Biocompatible, thermoresponsive, and biodegradable: simple preparation of “all-in-one” biorelevant polymers. Macromolecules, 2007. 40(24): p. 8540-8543.
29.Alanazi, F.K., A.A. Radwan, and I.A. Alsarra, Biopharmaceutical applications of nanogold. Saudi Pharmaceutical Journal, 2010. 18(4): p. 179-193.
30.Wagner, J., T. Tshikhudo, and J. Koehler, Microfluidic generation of metal nanoparticles by borohydride reduction. Chemical Engineering Journal, 2008. 135: p. S104-S109.
31.Cross, C., J. Hemminger, and R. Penner, Physical vapor deposition of one-dimensional nanoparticle arrays on graphite: seeding the electrodeposition of gold nanowires. Langmuir, 2007. 23(20): p. 10372-10379.
32.Suneetha, S.C.A., B.P.C. Raghupathy, and P. Suresh, Physicochemical characterization and cytotoxicity screening of a novel colloidal nanogold-based phenytoin conjugate. Scientia pharmaceutica, 2014. 82(4): p. 857-872.
33.Jain, G., S. Chakravartty, and A.G. Patel, Spleen?髹reserving distal pancreatectomy with and without splenic vessel ligation: a systematic review. HPB, 2013. 15(6): p. 403-410.
34.Papastefanaki, F., et al., Intraspinal delivery of polyethylene glycol-coated gold nanoparticles promotes functional recovery after spinal cord injury. Molecular Therapy, 2015. 23(6): p. 993-1002.
35.Lin, C.-M., et al., Hyaluronic acid-fabricated nanogold delivery of the inhibitor of apoptosis protein-2 siRNAs inhibits benzo [a] pyrene-induced oncogenic properties of lung cancer A549 cells. Nanotechnology, 2015. 26(10): p. 105101.
36.Zhao, X., Q. Huang, and Y. Jin, Gold nanorod delivery of LSD1 siRNA induces human mesenchymal stem cell differentiation. Materials Science and Engineering: C, 2015. 54: p. 142-149.
37.Borzenkov, M., et al., Thermal and chemical stability of thiol bonding on gold nanostars. Langmuir, 2015. 31(29): p. 8081-8091.
38.葉峻安, 奈米粒子與間葉幹細胞生物效能與交互作用機制之探討. 中國醫藥大學基礎醫學研究所學位論文, 2015: p. 1-224.
39.Huang, X. and M.A. El-Sayed, Gold nanoparticles: optical properties and implementations in cancer diagnosis and photothermal therapy. Journal of advanced research, 2010. 1(1): p. 13-28.
40.Lee, C., et al., Measurement of the elastic properties and intrinsic strength of monolayer graphene. science, 2008. 321(5887): p. 385-388.
41.Savage, N., Researchers Unzip Carbon Nanotubes to Make Ribbons of Graphene: A New Route to the Narrow Grapheme Ribbons Needed in Electronics. IEEE Spectrum, April, 2009. 16.
42.Nair, R.R., et al., Fine structure constant defines visual transparency of graphene. Science, 2008. 320(5881): p. 1308-1308.
43.Shen, H., et al., Biomedical applications of graphene. Theranostics, 2012. 2(3): p. 283.
44.Wang, Y., et al., Application of graphene-modified electrode for selective detection of dopamine. Electrochemistry Communications, 2009. 11(4): p. 889-892.
45.Jo, G., et al., The application of graphene as electrodes in electrical and optical devices. Nanotechnology, 2012. 23(11): p. 112001.
46.Liu, Q., J. Shi, and G. Jiang, Application of graphene in analytical sample preparation. TrAC Trends in Analytical Chemistry, 2012. 37: p. 1-11.
47.Park, S., et al., Colloidal suspensions of highly reduced graphene oxide in a wide variety of organic solvents. Nano letters, 2009. 9(4): p. 1593-1597.
48.Bagri, A., et al., Structural evolution during the reduction of chemically derived graphene oxide. Nature chemistry, 2010. 2(7): p. 581-587.
49.Liu, J., et al., Strong terahertz conductance of graphene nanoribbons under a magnetic field. Applied Physics Letters, 2008. 93(4): p. 041106.
50.Wang, X., L. Zhi, and K. M?刜len, Transparent, conductive graphene electrodes for dye-sensitized solar cells. Nano letters, 2008. 8(1): p. 323-327.
51.Khalil, I., et al., Graphene–Gold Nanoparticles Hybrid—Synthesis, Functionalization, and Application in a Electrochemical and Surface-Enhanced Raman Scattering Biosensor. Materials, 2016. 9(6): p. 406.
52.Akhavan, O., Graphene scaffolds in progressive nanotechnology/stem cell-based tissue engineering of the nervous system. Journal of Materials Chemistry B, 2016. 4(19): p. 3169-3190.
53.Kang, S., et al., Gold Nanoparticle/Graphene Oxide Hybrid Sheets Attached on Mesenchymal Stem Cells for Effective Photothermal Cancer Therapy. Chemistry of Materials, 2017. 29(8): p. 3461-3476.
54.Mahmoudian, M., et al., Synthesis and characterization of polypyrrole/Sn-doped TiO 2 nanocomposites (NCs) as a protective pigment. Applied Surface Science, 2011. 257(20): p. 8317-8325.
55.Nayak, T.R., et al., Graphene for controlled and accelerated osteogenic differentiation of human mesenchymal stem cells. ACS nano, 2011. 5(6): p. 4670-4678.
56.Kim, J., et al., Graphene-incorporated chitosan substrata for adhesion and differentiation of human mesenchymal stem cells. Journal of Materials Chemistry B, 2013. 1(7): p. 933-938.
57.Geng, X., et al., Interlayer catalytic exfoliation realizing scalable production of large-size pristine few-layer graphene. Scientific reports, 2013. 3.
58.Hua-Qiang, W., et al., Graphene applications in electronic and optoelectronic devices and circuits. Chinese Physics B, 2013. 22(9): p. 098106.
59.Algeri, M., et al., Mesenchymal stromal cells and chronic inflammatory bowel disease. Immunology letters, 2015. 168(2): p. 191-200.
60.Wiskemann, J., et al., Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood, 2011. 117(9): p. 2604-2613.
61.Mastropasqua, R., et al., Advanced morphological and functional magnetic resonance techniques in glaucoma. BioMed research international, 2015. 2015.
62.Bruder, O., et al., Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR Registry. JACC: Cardiovascular Imaging, 2011. 4(11): p. 1171-1176.
63.Forraz, N. and C. McGuckin, The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Proliferation, 2011. 44(s1): p. 60-69.
64.Kunkanjanawan, T., P. Noisa, and R. Parnpai, Modeling neurological disorders by human induced pluripotent stem cells. BioMed Research International, 2011. 2011.
65.Howard, D., et al., Tissue engineering: strategies, stem cells and scaffolds. Journal of anatomy, 2008. 213(1): p. 66-72.
66.Teng, Y.D., et al., Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences, 2002. 99(5): p. 3024-3029.
67.Ding, S., et al., A nano-micro alternating multilayer scaffold loading with rBMSCs and BMP-2 for bone tissue engineering. Colloids and Surfaces B: Biointerfaces, 2015. 133: p. 286-295.
68.Jiang, Q.-h., et al., Osteogenesis of rat mesenchymal stem cells and osteoblastic cells on strontium-doped nanohydroxyapatite-coated titanium surfaces. International Journal of Oral & Maxillofacial Implants, 2015. 30(2).
69.Lyu, C.-Q., et al., Induction of osteogenic differentiation of human adipose-derived stem cells by a novel self-supporting graphene hydrogel film and the possible underlying mechanism. ACS applied materials & interfaces, 2015. 7(36): p. 20245-20254.
70.Akhavan, O., et al., Rolled graphene oxide foams as three-dimensional scaffolds for growth of neural fibers using electrical stimulation of stem cells. Carbon, 2016. 97: p. 71-77.
71.Chen, G.-Y., et al., A graphene-based platform for induced pluripotent stem cells culture and differentiation. Biomaterials, 2012. 33(2): p. 418-427.
72.Li, C., et al., Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials, 2006. 27(16): p. 3115-3124.
73.柯智升, 利用多孔性 Collagen II/chondroitin sulfate/hyaluronic acid 載體誘導間葉幹細胞應用於組織工程軟骨之研究. 2008.
74.Sheng, Z.-H., et al., Catalyst-free synthesis of nitrogen-doped graphene via thermal annealing graphite oxide with melamine and its excellent electrocatalysis. ACS nano, 2011. 5(6): p. 4350-4358.
75.Tagusagawa, C., et al., Characterization of HNbWO6 and HTaWO6 metal oxide nanosheet aggregates as solid acid catalysts. The Journal of Physical Chemistry C, 2009. 113(18): p. 7831-7837.
76.Pumera, M., Electrochemistry of graphene: new horizons for sensing and energy storage. The Chemical Record, 2009. 9(4): p. 211-223.
77.Bom, D., et al., Thermogravimetric analysis of the oxidation of multiwalled carbon nanotubes: evidence for the role of defect sites in carbon nanotube chemistry. Nano Letters, 2002. 2(6): p. 615-619.
78.Kim, H., A.A. Abdala, and C.W. Macosko, Graphene/polymer nanocomposites. Macromolecules, 2010. 43(16): p. 6515-6530.
79.Young, R.J., et al., The mechanics of graphene nanocomposites: a review. Composites Science and Technology, 2012. 72(12): p. 1459-1476.
80.Eda, G. and M. Chhowalla, Graphene-based composite thin films for electronics. Nano Letters, 2009. 9(2): p. 814-818.
81.Balandin, A., et al., Extremely high thermal conductivity of graphene: experimental study. arXiv preprint arXiv:0802.1367, 2008.
82.Tang, B. and G. Hu, Two kinds of graphene-based composites for photoanode applying in dye-sensitized solar cell. Journal of Power Sources, 2012. 220: p. 95-102.
83.Nosheen, E., S.M. Shah, and Z. Iqbal, Ru-dye grafted CdS and reduced graphene oxide Ru/CdS/rGO composite: An efficient and photo tuneable electrode material for solid state dye sensitized polymer solar cells. Journal of Photochemistry and Photobiology B: Biology, 2017. 167: p. 117-127.
84.Shao, Y., et al., Graphene based electrochemical sensors and biosensors: a review. Electroanalysis, 2010. 22(10): p. 1027-1036.
85.Zhu, Z., et al., A critical review of glucose biosensors based on carbon nanomaterials: carbon nanotubes and graphene. Sensors, 2012. 12(5): p. 5996-6022.
86.Kuilla, T., et al., Recent advances in graphene based polymer composites. Progress in polymer science, 2010. 35(11): p. 1350-1375.
87.Cai, D. and M. Song, Recent advance in functionalized graphene/polymer nanocomposites. Journal of Materials Chemistry, 2010. 20(37): p. 7906-7915.
88.Kuila, T., et al., Chemical functionalization of graphene and its applications. Progress in Materials Science, 2012. 57(7): p. 1061-1105.
89.Bai, H., C. Li, and G. Shi, Functional composite materials based on chemically converted graphene. Advanced Materials, 2011. 23(9): p. 1089-1115.
90.Sanchez, V.C., et al., Biological interactions of graphene-family nanomaterials: an interdisciplinary review. Chemical research in toxicology, 2011. 25(1): p. 15-34.
91.Wang, Y., et al., Graphene and graphene oxide: biofunctionalization and applications in biotechnology. Trends in biotechnology, 2011. 29(5): p. 205-212.
92.Born, G.V.R., Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature, 1962. 194(4832): p. 927-929.
93.Ryu, S. and B.-S. Kim, Culture of neural cells and stem cells on graphene. Tissue Eng Regen Med, 2013. 10(2): p. 39-46.
94.Nishida, E., et al., Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket. International journal of nanomedicine, 2016. 11: p. 2265.
95.Domanska, U.M., et al., A review on CXCR4/CXCL12 axis in oncology: no place to hide. European journal of cancer, 2013. 49(1): p. 219-230.
96.Diaconeasa, Z., et al., Antiproliferative and antioxidant properties of anthocyanin rich extracts from blueberry and blackcurrant juice. International journal of molecular sciences, 2015. 16(2): p. 2352-2365.
97.Rastogi, R.P., et al., Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2′, 7′-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochemical and biophysical research communications, 2010. 397(3): p. 603-607.
98.He, Y.-Y. and D.-P. H?黌er, UV-B-induced formation of reactive oxygen species and oxidative damage of the cyanobacterium Anabaena sp.: protective effects of ascorbic acid and N-acetyl-L-cysteine. Journal of Photochemistry and Photobiology B: Biology, 2002. 66(2): p. 115-124.
99.Shams, E., et al., Polyurethane/siloxane membranes containing graphene oxide nanoplatelets as antimicrobial wound dressings: in vitro and in vivo evaluations. Journal of Materials Science: Materials in Medicine, 2017. 28(5): p. 75.
100.Ju, A., Y.-C. Cho, and S. Cho, Methanol extracts of Xanthium sibiricum roots inhibit inflammatory responses via the inhibition of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in murine macrophages. Journal of ethnopharmacology, 2015. 174: p. 74-81.
101.Ko, T.-M., J.-C. Lin, and S.L. Cooper, Surface characterization and platelet adhesion studies of plasma-carboxylated polyethylene. Journal of colloid and interface science, 1993. 156(1): p. 207-217.
102.BROWN, F., et al., Quality of biotechnological products: Derivation and characterisation of cell substrates used for production of biotechnological. Developments in biological standardization, 1998(93): p. 223-234.
103.Ho, T.K., et al., Stromal-cell-derived factor-1 (SDF-1)/CXCL12 as potential target of therapeutic angiogenesis in critical leg ischaemia. Cardiology research and practice, 2012. 2012.
104.Yu, Q., et al., SDF-1α/CXCR4 axis mediates the migration of mesenchymal stem cells to the hypoxic-ischemic brain lesion in a rat model. Cell Journal (Yakhteh), 2015. 16(4): p. 440.
105.Johnson, C. and Z.S. Galis, Matrix metalloproteinase-2 and− 9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization. Arteriosclerosis, thrombosis, and vascular biology, 2004. 24(1): p. 54-60.
106.Hsieh, T., et al., Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials. International journal of oncology, 1999. 15(2): p. 245-297.
107.Cappella, P., et al., Cell cycle effects of gemcitabine. International journal of cancer, 2001. 93(3): p. 401-408.
108.Bratton, D.L., et al., Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. Journal of Biological Chemistry, 1997. 272(42): p. 26159-26165.
109.Rieger, A.M., et al., Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. Journal of visualized experiments: JoVE, 2011(50).
110.Kang, E.-S., et al., Guiding osteogenesis of mesenchymal stem cells using carbon-based nanomaterials. Nano Convergence, 2017. 4(1): p. 2.
111.Yi, H., et al., Recent advances in nano scaffolds for bone repair. Bone research, 2016. 4: p. 16050.
112.Sawai, H. and N. Domae, Discrimination between primary necrosis and apoptosis by necrostatin-1 in Annexin V-positive/propidium iodide-negative cells. Biochemical and biophysical research communications, 2011. 411(3): p. 569-573.
113.Wang, J.-j., et al., Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor. Journal of Zhejiang University-Science B, 2009. 10(5): p. 355-367.
114.Roobrouck, V.D., et al., Differentiation potential of human postnatal mesenchymal stem cells, mesoangioblasts, and multipotent adult progenitor cells reflected in their transcriptome and partially influenced by the culture conditions. Stem Cells, 2011. 29(5): p. 871-882.
PART-2
1.Loizidou, M. and A. Seifalian, Nanotechnology and its applications in surgery. British journal of surgery, 2010. 97(4): p. 463-465.
2.Sato, M. and T.J. Webster, Nanobiotechnology: implications for the future of nanotechnology in orthopedic applications. Expert review of medical devices, 2004. 1(1): p. 105-114.
3.Saraiva, S.M. and J.F. de Oliveira, Control of particle size in the preparation of colloidal gold. Journal of dispersion science and technology, 2002. 23(6): p. 837-844.
4.Helmersson, U., et al., Ionized physical vapor deposition (IPVD): A review of technology and applications. Thin Solid Films, 2006. 513(1): p. 1-24.
5.Raring, J., A. Chakraborty, and C. Poblenz, Rapid Growth Method and Structures for Gallium and Nitrogen Containing Ultra-Thin Epitaxial Structures for Devices. 2010, Google Patents.
6.Bae, S., et al., Roll-to-roll production of 30-inch graphene films for transparent electrodes. Nature nanotechnology, 2010. 5(8): p. 574-578.
7.Das, S., et al., In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration. Biomaterials, 2015. 62: p. 66-75.
8.Hung, H.-S., et al., Biocompatibility and favorable response of mesenchymal stem cells on fibronectin-gold nanocomposites. PloS one, 2013. 8(6): p. e65738.
9.Tashiro, K., et al., Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science, 1993. 261.
10.Rao, C.R., et al., Metal nanoparticles and their assemblies. Chemical Society Reviews, 2000. 29(1): p. 27-35.
11.Scadden, D.T., The stem-cell niche as an entity of action. Nature, 2006. 441(7097): p. 1075.
12.Zhao, W., et al., Cell-surface sensors for real-time probing of cellular environments. Nature nanotechnology, 2011. 6(8): p. 524-531.
13.Hay, E.D., Cell biology of extracellular matrix. 2013: Springer Science & Business Media.
14.Reilly, G.C. and A.J. Engler, Intrinsic extracellular matrix properties regulate stem cell differentiation. Journal of biomechanics, 2010. 43(1): p. 55-62.
15.Aggarwal, P., et al., Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Advanced drug delivery reviews, 2009. 61(6): p. 428-437.
16.Zhao, X., Q. Huang, and Y. Jin, Gold nanorod delivery of LSD1 siRNA induces human mesenchymal stem cell differentiation. Materials Science and Engineering: C, 2015. 54: p. 142-149.
17.Zorlutuna, P., N.E. Vrana, and A. Khademhosseini, The expanding world of tissue engineering: the building blocks and new applications of tissue engineered constructs. IEEE reviews in biomedical engineering, 2013. 6: p. 47-62.
18.Rosenthal, N. and L. Tsao, Helping the heart to heal with stem cells. Nature medicine, 2001. 7(4): p. 412-414.
19.Satyam, A., et al., Macromolecular crowding meets tissue engineering by self?駮ssembly: A paradigm shift in regenerative medicine. Advanced materials, 2014. 26(19): p. 3024-3034.
20.Strauer, B.E., et al., Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 2002. 106(15): p. 1913-1918.
21.Suneetha, S.C.A., B.P.C. Raghupathy, and P. Suresh, Physicochemical characterization and cytotoxicity screening of a novel colloidal nanogold-based phenytoin conjugate. Scientia pharmaceutica, 2014. 82(4): p. 857-872.
22.Via, A.G., A. Frizziero, and F. Oliva, Biological properties of mesenchymal Stem Cells from different sources. Muscles, Ligaments and Tendons Journal, 2012. 2(3): p. 154.
23.Wang, L., et al., Synergic effects of crypt-like topography and ECM proteins on intestinal cell behavior in collagen based membranes. Biomaterials, 2010. 31(29): p. 7586-7598.
24.Zaporojtchenko, V., et al., Physico-chemical and antimicrobial properties of co-sputtered Ag–Au/PTFE nanocomposite coatings. Nanotechnology, 2006. 17(19): p. 4904.
25.Zhang, L., et al., Glycitin regulates osteoblasts through TGF-β or AKT signaling pathways in bone marrow stem cells. Experimental and therapeutic medicine, 2016. 12(5): p. 3063-3067.
26.Yi, C., et al., Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. Acs Nano, 2010. 4(11): p. 6439-6448.
27.Hung, H.-S., et al., Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites. Biomaterials, 2014. 35(25): p. 6810-6821.
28.Huang, C.-Y., et al., Enhanced migration of wharton’s jelly mesenchymal stem cells grown on polyurethane nanocomposites. Journal of Medical and Biological Engineering, 2013. 33(2): p. 139-148.
29.Hung, H.-S., et al., In vitro study of a novel nanogold-collagen composite to enhance the mesenchymal stem cell behavior for vascular regeneration. PloS one, 2014. 9(8): p. e104019.
30.Abbey, C.A. and K.J. Bayless, Matrix density alters zyxin phosphorylation, which limits peripheral process formation and extension in endothelial cells invading 3D collagen matrices. Matrix Biology, 2014. 38: p. 36-47.
31.A?岥l, Y., et al., Effects of zoledronate on irradiated bone in vivo: Analysis of the collagen types I, V and their cross-links lysylpyridinoline, hydroxylysylpyridinoline and hydroxyproline. Calcified tissue international, 2013. 92(3): p. 251-260.
32.Amini, A.R., C.T. Laurencin, and S.P. Nukavarapu, Bone tissue engineering: recent advances and challenges. Critical Reviews?? in Biomedical Engineering, 2012. 40(5).
33.Bleul, C.C., et al., A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). Journal of Experimental Medicine, 1996. 184(3): p. 1101-1109.
34.Chen, M., M. Przyborowski, and F. Berthiaume, Stem cells for skin tissue engineering and wound healing. Critical Reviews?? in Biomedical Engineering, 2009. 37(4-5).
35.Dickerson, E.B., et al., Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. Cancer letters, 2008. 269(1): p. 57-66.
36.Domanska, U.M., et al., A review on CXCR4/CXCL12 axis in oncology: no place to hide. European journal of cancer, 2013. 49(1): p. 219-230.
37.Fleischer, M., et al., Tailoring gold nanostructures for near-field optical applications. Nanotechnology, 2010. 21(6): p. 065301.
38.Fujie, T., et al., Micropatterned polymeric nanosheets for local delivery of an engineered epithelial monolayer. Advanced Materials, 2014. 26(11): p. 1699-1705.
39.Galicka, A., et al., Anethole prevents hydrogen peroxide-induced apoptosis and collagen metabolism alterations in human skin fibroblasts. Molecular and cellular biochemistry, 2014. 394(1-2): p. 217-224.
40.Boudriot, U., et al., Electrospinning approaches toward scaffold engineering—a brief overview. Artificial organs, 2006. 30(10): p. 785-792.
41.Hsieh, S.-C., et al., Prominent Vascularization Capacity of Mesenchymal Stem Cells in Collagen–Gold Nanocomposites. ACS applied materials & interfaces, 2016. 8(42): p. 28982-29000.
42.Gr?刡dker, C., et al., Inhibition of SDF-1/CXCR4-induced epithelial–mesenchymal transition by kisspeptin-10. Breast cancer research and treatment, 2015. 152(1): p. 41-50.
43.Huang, X., et al., Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers. Journal of biomedical optics, 2010. 15(5): p. 058002-058002-7.
44.Francillon?鞔ieillot, H., et al., Microstructure and mineralization of vertebrate skeletal tissues. Skeletal biomineralization: patterns, processes and evolutionary trends, 1990: p. 175-234.
45.Jung, D., et al., Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells. Journal of nanobiotechnology, 2012. 10(1): p. 23.
46.Ma, Q., et al., Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4-and SDF-1-deficient mice. Proceedings of the National Academy of Sciences, 1998. 95(16): p. 9448-9453.
47.Malgieri, A., et al., Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. International journal of clinical and experimental medicine, 2010. 3(4): p. 248.
48.Murasawa, Y., T. Hayashi, and P.-C. Wang, The role of type V collagen fibril as an ECM that induces the motility of glomerular endothelial cells. Experimental cell research, 2008. 314(20): p. 3638-3653.
49.N?鮑ar Dur?鴨, E., D. Ludevid M?朧ica, and C. Poschenrieder, Characterization of the maize protein ZmSTOP1 and its role in drought stress response. 2015.
50.Oswald, J., et al., Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem cells, 2004. 22(3): p. 377-384.
51.Pablos, J.L., et al., Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin. The American journal of pathology, 1999. 155(5): p. 1577-1586.
52.Kitaori, T., et al., Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis & Rheumatology, 2009. 60(3): p. 813-823.
53.Askari, A.T., et al., Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. The Lancet, 2003. 362(9385): p. 697-703.
54.Pathak, S., et al., Hybrid congregation of islet single cells and curcumin-loaded polymeric microspheres as an interventional strategy to overcome apoptosis associated with pancreatic islets transplantation. ACS applied materials & interfaces, 2016. 8(39): p. 25702-25713.
55.Payne, E.K., et al., Multipole plasmon resonances in gold nanorods. The Journal of Physical Chemistry B, 2006. 110(5): p. 2150-2154.
56.Berbeco, R.I., W. Ngwa, and G.M. Makrigiorgos, Localized dose enhancement to tumor blood vessel endothelial cells via megavoltage X-rays and targeted gold nanoparticles: new potential for external beam radiotherapy. International Journal of Radiation Oncology* Biology* Physics, 2011. 81(1): p. 270-276.
57.Rahman, W.N., et al., Polymer gels impregnated with gold nanoparticles implemented for measurements of radiation dose enhancement in synchrotron and conventional radiotherapy type beams. Australasian physical & engineering sciences in medicine, 2012. 35(3): p. 301-309.
58.Caplan, A.I., All MSCs are pericytes? Cell stem cell, 2008. 3(3): p. 229-230.
59.Crisan, M., et al., A perivascular origin for mesenchymal stem cells in multiple human organs. Cell stem cell, 2008. 3(3): p. 301-313.
60.da Silva Meirelles, L., et al., Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine & growth factor reviews, 2009. 20(5): p. 419-427.
61.Gu, H.-Y., et al., The immobilization of hepatocytes on 24nm-sized gold colloid for enhanced hepatocytes proliferation. Biomaterials, 2004. 25(17): p. 3445-3451.
62.Nimi, N., W. Paul, and C.P. Sharma, Blood protein adsorption and compatibility studies of gold nanoparticles. Gold Bulletin, 2011. 44(1): p. 15-20.
63.Chen, T.-K., Y.-I. Tien, and K.-H. Wei, Synthesis and characterization of novel segmented polyurethane/clay nanocomposites. Polymer, 2000. 41(4): p. 1345-1353.
64.Cummings, C.L., et al., Properties of engineered vascular constructs made from collagen, fibrin, and collagen–fibrin mixtures. Biomaterials, 2004. 25(17): p. 3699-3706.
65.Ho, T.-T., Y.-C. Lin, and S.-h. Hsu, Human endothelial cell response to polyurethane–gold nanocomposites. Gold Bulletin, 2012. 45(3): p. 161-170.
66.Horovitz, O., et al., Protein binding to gold autoassembled films. Gold bulletin, 2007. 40(4): p. 295-304.
67.Hung, H.-S., et al., The behavior of endothelial cells on polyurethane nanocomposites and the associated signaling pathways. Biomaterials, 2009. 30(8): p. 1502-1511.
68.Liu, P., et al., Tissue?駰ngineered skin containing mesenchymal stem cells improves burn wounds. Artificial organs, 2008. 32(12): p. 925-931.
69.Alamein, M.A., et al., Mass production of nanofibrous extracellular matrix with controlled 3D morphology for large-scale soft tissue regeneration. Tissue Engineering Part C: Methods, 2012. 19(6): p. 458-472.
70.Hu, Q., et al., FABRICATION OF 3D POLYMER-METAL NANO-COMPOSITES IN A SINGLE STEP BY TWO-PHOTON INDUCED POLYMERISATION AND METAL SALT REDUCTION.
71.Storhoff, J.J., et al., One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J. Am. Chem. Soc, 1998. 120(9): p. 1959-1964.
72.Wei, G.-T., F.-K. Liu, and C.C. Wang, Shape separation of nanometer gold particles by size-exclusion chromatography. Analytical chemistry, 1999. 71(11): p. 2085-2091.
73.Bacakova, L., K. Novotn??, and M. Parizek, Polysaccharides as cell carriers for tissue engineering: the use of cellulose in vascular wall reconstruction. Physiological research, 2014. 63: p. S29.
74.Cencioni, C., M.C. Capogrossi, and M. Napolitano, The SDF-1/CXCR4 axis in stem cell preconditioning. Cardiovascular research, 2012. 94(3): p. 400-407.
75.Jeong, J.W., et al., Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up?霒egulation, ROS Generation, Modulation of Bcl??2 and IAP Family Members. Phytotherapy Research, 2015. 29(10): p. 1516-1524.
76.Kalyanaraman, B., et al., Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radical Biology and Medicine, 2012. 52(1): p. 1-6.
77.Li, M., et al., SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways. Scientific reports, 2017. 7: p. 40161.
78.Li, Y., et al., Cell migration microfluidics for electrotaxis-based heterogeneity study of lung cancer cells. Biosensors and Bioelectronics, 2017. 89: p. 837-845.
79.Moreno-Arotzena, O., et al., Inducing chemotactic and haptotactic cues in microfluidic devices for three-dimensional in vitro assays. Biomicrofluidics, 2014. 8(6): p. 064122.
80.Rota, C., C.F. Chignell, and R.P. Mason, Evidence for free radical formation during the oxidation of 2′-7′-dichlorofluorescin to the fluorescent dye 2′-7′-dichlorofluorescein by horseradish peroxidase:: Possible implications for oxidative stress measurements. Free Radical Biology and Medicine, 1999. 27(7): p. 873-881.
81.Gialeli, C., A.D. Theocharis, and N.K. Karamanos, Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. The FEBS journal, 2011. 278(1): p. 16-27.
82.Zhang, D., et al., Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d). Proceedings of the National Academy of Sciences, 1994. 91(18): p. 8447-8451.
83.Jabłońska-Trypuć, A., M. Matejczyk, and S. Rosochacki, Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. Journal of enzyme inhibition and medicinal chemistry, 2016. 31(sup1): p. 177-183.
84.Wang, J.D. and P.A. Levin, Metabolism, cell growth and the bacterial cell cycle. Nature Reviews Microbiology, 2009. 7(11): p. 822-827.
85.Lilly, M.A. and R.J. Duronio, New insights into cell cycle control from the Drosophila endocycle. Oncogene, 2005. 24(17): p. 2765-2775.
86.Meers, P. and T. Mealy, Phospholipid determinants for annexin V binding sites and the role of tryptophan 187. Biochemistry, 1994. 33(19): p. 5829-5837.
87.Koopman, G., et al., Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood, 1994. 84(5): p. 1415-1420.
88.Cecchini, M.J., M. Amiri, and F.A. Dick, Analysis of cell cycle position in mammalian cells. Journal of visualized experiments: JoVE, 2012(59).
89.Hirschi, A., et al., An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nature structural & molecular biology, 2010. 17(99): p. 1051-1057.
90.Buck, S.B., et al., Detection of S-phase cell cycle progression using 5-ethynyl-2''-deoxyuridine incorporation with click chemistry, an alternative to using 5-bromo-2''-deoxyuridine antibodies. Biotechniques, 2008. 44(7): p. 927-929.
91.Wang, Q., et al., Decreased proliferation ability and differentiation potential of mesenchymal stem cells of osteoporosis rat. Asian Pacific journal of tropical medicine, 2014. 7(5): p. 358-363.
92.Saulite, L., et al., Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery. Beilstein Journal of Nanotechnology, 2017. 8(1): p. 1218-1230.
93.Sasaki, M., et al., Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. the Journal of immunology, 2008. 180(4): p. 2581-2587.
94.Kawaguchi, H., et al., Enhancement of periodontal tissue regeneration by transplantation of bone marrow mesenchymal stem cells. Journal of periodontology, 2004. 75(9): p. 1281-1287.
95.Hinz, B., Formation and function of the myofibroblast during tissue repair. Journal of Investigative Dermatology, 2007. 127(3): p. 526-537.
96.Griffith, L.G. and G. Naughton, Tissue engineering--current challenges and expanding opportunities. Science, 2002. 295(5557): p. 1009-1014.
97.McBride, J.D., et al., Bone marrow mesenchymal stem cell-derived CD63+ exosomes transport Wnt3a exteriorly and enhance dermal fibroblast proliferation, migration and angiogenesis in vitro. Stem Cells and Development, 2017(ja).
98.Wang, J.-j., et al., Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor. Journal of Zhejiang University-Science B, 2009. 10(5): p. 355-367.
99.Falcone, S., et al., Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events. J Cell Sci, 2006. 119(22): p. 4758-4769.
100.Swazey, J.P., Chlorpromazine in psychiatry: A study of therapeutic innovation. 1974: The MIT Press.
101.Rodal, S.K., et al., Extraction of cholesterol with methyl-β-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Molecular biology of the cell, 1999. 10(4): p. 961-974.
102.Madara, J.L., D. Barenberg, and S. Carlson, Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. The Journal of cell biology, 1986. 102(6): p. 2125-2136.
103.Yamamoto, A., et al., Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell structure and function, 1998. 23(1): p. 33-42.
104.Nabi, I.R. and P.U. Le, Caveolae/raft-dependent endocytosis. The Journal of cell biology, 2003. 161(4): p. 673-677.
105.Sanchez, A., Analysis of filovirus entry into vero e6 cells, using inhibitors of endocytosis, endosomal acidification, structural integrity, and cathepsin (B and L) activity. The Journal of infectious diseases, 2007. 196(Supplement_2): p. S251-S258.
106.Ma, X., et al., Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. ACS nano, 2011. 5(11): p. 8629-8639.