請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16189完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 何佳安(Ja-An Annie Ho) | |
| dc.contributor.author | Yi-Te Chou | en |
| dc.contributor.author | 周易德 | zh_TW |
| dc.date.accessioned | 2021-06-07T18:04:23Z | - |
| dc.date.copyright | 2021-02-22 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-02-04 | |
| dc.identifier.citation | 1 Rockwood CA Jr, G. D., Bucholz RW. Rockwood and Green's fractures in adults. Vol. 1 (1996). 2 Colon-Emeric, C. S. Saag, K. G. Osteoporotic fractures in older adults. Best Pract Res Clin Rheumatol 20, 695-706, doi:10.1016/j.berh.2006.04.004 (2006). 3 OlaOlorun, D. A., Oladiran, I. O. Adeniran, A. Complications of fracture treatment by traditional bonesetters in southwest Nigeria. Fam Pract 18, 635-637 (2001). 4 Weiner, S., Traub, W. Wagner, H. D. Lamellar bone: structure-function relations. J Struct Biol 126, 241-255, doi:10.1006/jsbi.1999.4107 (1999). 5 Buckwalter, J. A. Cooper, R. R. Bone structure and function. Instr Course Lect 36, 27-48 (1987). 6 Hall, J. Textbook of Medical Physiology. 12 edn, 957–960 (2011). 7 Feng, X. Chemical and Biochemical Basis of Cell-Bone Matrix Interaction in Health and Disease. Curr Chem Biol 3, 189-196, doi:10.2174/187231309788166398 (2009). 8 Carter, D. R. Hayes, W. C. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg Am 59, 954-962 (1977). 9 Elfenbein, G. J. et al. Immune system reconstitution following allogeneic bone marrow transplantation in man: a multiparameter analysis. Transplant Proc 8, 641-646 (1976). 10 Kricun, M. E. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 14, 10-19 (1985). 11 OpenStax. Anatomy and physiology. (2013). 12 Marsell, R. Einhorn, T. A. The biology of fracture healing. Injury 42, 551-555, doi:10.1016/j.injury.2011.03.031 (2011). 13 Gerstenfeld, L. C., Cullinane, D. M., Barnes, G. L., Graves, D. T. Einhorn, T. A. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88, 873-884, doi:10.1002/jcb.10435 (2003). 14 Cho, T. J., Gerstenfeld, L. C. Einhorn, T. A. Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17, 513-520, doi:10.1359/jbmr.2002.17.3.513 (2002). 15 Sfeir C, H. L., Doll BA, Azari K, Hollinger JO. Fracture repair. (2005). 16 Kon, T. et al. Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner Res 16, 1004-1014, doi:10.1359/jbmr.2001.16.6.1004 (2001). 17 Lee, S. K. Lorenzo, J. Cytokines regulating osteoclast formation and function. Curr Opin Rheumatol 18, 411-418, doi:10.1097/01.bor.0000231911.42666.78 (2006). 18 Lienau, J. et al. Differential Regulation of Blood Vessel Formation between Standard and Delayed Bone Healing. J Orthop Res 27, 1133-1140, doi:10.1002/jor.20870 (2009). 19 Schmidt-Bleek, K. et al. Cellular Composition of the Initial Fracture Hematoma Compared to a Muscle Hematoma: A Study in Sheep. J Orthop Res 27, 1147-1151, doi:10.1002/jor.20901 (2009). 20 Lienau, J. et al. Insight into the Molecular Pathophysiology of Delayed Bone Healing in a Sheep Model. Tissue Eng Pt A 16, 191-199, doi:10.1089/ten.tea.2009.0187 (2010). 21 Granero-Molto, F. et al. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells 27, 1887-1898, doi:10.1002/stem.103 (2009). 22 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 Rheum 60, 813-823, doi:10.1002/art.24330 (2009). 23 Ceradini, D. J. et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10, 858-864, doi:10.1038/nm1075 (2004). 24 Wan, C. et al. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A 105, 686-691, doi:10.1073/pnas.0708474105 (2008). 25 Einhorn, T. A. The cell and molecular biology of fracture healing. Clin Orthop Relat Res, S7-21 (1998). 26 Gerstenfeld, L. C. et al. Three-dimensional reconstruction of fracture callus morphogenesis. J Histochem Cytochem 54, 1215-1228, doi:10.1369/jhc.6A6959.2006 (2006). 27 Keramaris, N. C., Calori, G. M., Nikolaou, V. S., Schemitsch, E. H. Giannoudis, P. V. Fracture vascularity and bone healing: a systematic review of the role of VEGF. Injury 39 Suppl 2, S45-57, doi:10.1016/S0020-1383(08)70015-9 (2008). 28 Ai-Aql, Z. S., Alagl, A. S., Graves, D. T., Gerstenfeld, L. C. Einhorn, T. A. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res 87, 107-118, doi:10.1177/154405910808700215 (2008). 29 Tsiridis, E., Upadhyay, N. Giannoudis, P. Molecular aspects of fracture healing: which are the important molecules? Injury 38 Suppl 1, S11-25, doi:10.1016/j.injury.2007.02.006 (2007). 30 Lehmann, W. et al. Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing. Bone 36, 300-310, doi:10.1016/j.bone.2004.10.010 (2005). 31 Mountziaris, P. M. Mikos, A. G. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev 14, 179-186, doi:10.1089/ten.teb.2008.0038 (2008). 32 Wendeberg, B. Mineral metabolism of fractures of the tibia in man studied with external counting of Sr85. Acta Orthop Scand Suppl 52, 1-79 (1961). 33 Mescher, A. L. Junqueira's Basic Histology. 14 edn. 34 Memarsadeghi, M. et al. Occult scaphoid fractures: comparison of multidetector CT and MR imaging--initial experience. Radiology 240, 169-176, doi:10.1148/radiol.2401050412 (2006). 35 Koo, T. K., Chao, E. Y. Mak, A. F. Development and validation of a new approach for computer-aided long bone fracture reduction using unilateral external fixator. J Biomech 39, 2104-2112, doi:10.1016/j.jbiomech.2005.06.002 (2006). 36 Tressler, M. A. et al. Bone morphogenetic protein-2 compared to autologous iliac crest bone graft in the treatment of long bone nonunion. Orthopedics 34, e877-884, doi:10.3928/01477447-20111021-09 (2011). 37 Finkemeier, C. G. Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 84-A, 454-464 (2002). 38 Tian, H. et al. Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration. ACS Nano 10, 7362-7369, doi:10.1021/acsnano.5b07950 (2016). 39 Paley, D. et al. Ilizarov treatment of tibial nonunions with bone loss. Clin Orthop Relat Res, 146-165 (1989). 40 Paley, D. Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin Orthop Relat Res, 81-104 (1990). 41 Florencio-Silva, R., Sasso, G. R., Sasso-Cerri, E., Simoes, M. J. Cerri, P. S. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed Res Int 2015, 421746, doi:10.1155/2015/421746 (2015). 42 Clarke, B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3 Suppl 3, S131-139, doi:10.2215/CJN.04151206 (2008). 43 Udagawa, N. et al. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A 87, 7260-7264 (1990). 44 Tanaka, Y., Nakayamada, S. Okada, Y. Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy 4, 325-328 (2005). 45 Glantschnig, H., Fisher, J. E., Wesolowski, G., Rodan, G. A. Reszka, A. A. M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ 10, 1165-1177, doi:10.1038/sj.cdd.4401285 (2003). 46 Boyce, B. F. Xing, L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473, 139-146, doi:10.1016/j.abb.2008.03.018 (2008). 47 Einhorn, T. A. Gerstenfeld, L. C. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol 11, 45-54, doi:10.1038/nrrheum.2014.164 (2015). 48 Yang, J., Zhang, L., Yu, C., Yang, X. F. Wang, H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res 2, 1, doi:10.1186/2050-7771-2-1 (2014). 49 Biswas, S. K. Mantovani, A. Orchestration of metabolism by macrophages. Cell Metab 15, 432-437, doi:10.1016/j.cmet.2011.11.013 (2012). 50 Davies, L. C., Jenkins, S. J., Allen, J. E. Taylor, P. R. Tissue-resident macrophages. Nat Immunol 14, 986-995, doi:10.1038/ni.2705 (2013). 51 Alexander, K. A. et al. Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res 26, 1517-1532, doi:10.1002/jbmr.354 (2011). 52 Schlundt, C. et al. Macrophages in bone fracture healing: Their essential role in endochondral ossification. Bone, doi:10.1016/j.bone.2015.10.019 (2015). 53 Italiani, P. Boraschi, D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol 5, 514, doi:10.3389/fimmu.2014.00514 (2014). 54 Schell, H. et al. The haematoma and its role in bone healing. J Exp Orthop 4, 5, doi:10.1186/s40634-017-0079-3 (2017). 55 Loi, F. et al. The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. Stem Cell Res Ther 7, 15, doi:10.1186/s13287-016-0276-5 (2016). 56 Atri, C., Guerfali, F. Z. Laouini, D. Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. Int J Mol Sci 19, doi:ARTN 1801 10.3390/ijms19061801 (2018). 57 'Plenty of room' revisited. Nat Nanotechnol 4, 781, doi:10.1038/nnano.2009.356 (2009). 58 Salata, O. Applications of nanoparticles in biology and medicine. J Nanobiotechnology 2, 3, doi:10.1186/1477-3155-2-3 (2004). 59 Murthy, S. K. Nanoparticles in modern medicine: state of the art and future challenges. Int J Nanomedicine 2, 129-141 (2007). 60 Watkins, R., Wu, L., Zhang, C., Davis, R. M. Xu, B. Natural product-based nanomedicine: recent advances and issues. Int J Nanomedicine 10, 6055-6074, doi:10.2147/IJN.S92162 (2015). 61 Davis, M. E., Chen, Z. G. Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7, 771-782, doi:10.1038/nrd2614 (2008). 62 Cole, L. E., Vargo-Gogola, T. Roeder, R. K. Targeted delivery to bone and mineral deposits using bisphosphonate ligands. Adv Drug Deliv Rev 99, 12-27, doi:10.1016/j.addr.2015.10.005 (2016). 63 Sun, Y. et al. Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery. ACS Nano 10, 5759-5768, doi:10.1021/acsnano.5b07828 (2016). 64 Holyoak, D. T., Tian, Y. F., van der Meulen, M. C. Singh, A. Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment. Ann Biomed Eng 44, 2062-2075, doi:10.1007/s10439-016-1600-z (2016). 65 Farokhi, M. et al. Importance of dual delivery systems for bone tissue engineering. J Control Release 225, 152-169, doi:10.1016/j.jconrel.2016.01.033 (2016). 66 Makadia, H. K. Siegel, S. J. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel) 3, 1377-1397, doi:10.3390/polym3031377 (2011). 67 Bouissou, C., Rouse, J. J., Price, R. van der Walle, C. F. The influence of surfactant on PLGA microsphere glass transition and water sorption: remodeling the surface morphology to attenuate the burst release. Pharm Res 23, 1295-1305, doi:10.1007/s11095-006-0180-2 (2006). 68 Jain, R. A. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21, 2475-2490 (2000). 69 Ruhe, P. Q. et al. rhBMP-2 release from injectable poly(DL-lactic-co-glycolic acid)/calcium-phosphate cement composites. J Bone Joint Surg Am 85-A Suppl 3, 75-81 (2003). 70 Allison, S. D. Effect of structural relaxation on the preparation and drug release behavior of poly(lactic-co-glycolic)acid microparticle drug delivery systems. J Pharm Sci 97, 2022-2035, doi:10.1002/jps.21124 (2008). 71 Mundargi, R. C., Babu, V. R., Rangaswamy, V., Patel, P. Aminabhavi, T. M. Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. J Control Release 125, 193-209, doi:10.1016/j.jconrel.2007.09.013 (2008). 72 Mohamed, F. van der Walle, C. F. Engineering biodegradable polyester particles with specific drug targeting and drug release properties. J Pharm Sci 97, 71-87, doi:10.1002/jps.21082 (2008). 73 Ogston, A. G. Stanier, J. E. The physiological function of hyaluronic acid in synovial fluid; viscous, elastic and lubricant properties. J Physiol 119, 244-252 (1953). 74 Newberry, S. J. et al. in Systematic Review for Effectiveness of Hyaluronic Acid in the Treatment of Severe Degenerative Joint Disease (DJD) of the Knee AHRQ Technology Assessments (2015). 75 Goa, K. L. Benfield, P. Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs 47, 536-566 (1994). 76 Allison, D. D. Grande-Allen, K. J. Review. Hyaluronan: a powerful tissue engineering tool. Tissue Eng 12, 2131-2140, doi:10.1089/ten.2006.12.2131 (2006). 77 Choi, K. Y. et al. Self-assembled hyaluronic acid nanoparticles for active tumor targeting. Biomaterials 31, 106-114, doi:10.1016/j.biomaterials.2009.09.030 (2010). 78 Yu, M. et al. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells. Nanoscale 5, 178-183, doi:10.1039/c2nr32145a (2013). 79 Bauer, C. et al. Chondroprotective effect of high-molecular-weight hyaluronic acid on osteoarthritic chondrocytes in a co-cultivation inflammation model with M1 macrophages. J Inflamm (Lond) 13, 31, doi:10.1186/s12950-016-0139-y (2016). 80 Ariyoshi, W., Okinaga, T., Knudson, C. B., Knudson, W. Nishihara, T. High molecular weight hyaluronic acid regulates osteoclast formation by inhibiting receptor activator of NF-kappaB ligand through Rho kinase. Osteoarthritis Cartilage 22, 111-120, doi:10.1016/j.joca.2013.10.013 (2014). 81 Ariyoshi, W. et al. Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid. J Biol Chem 280, 18967-18972, doi:10.1074/jbc.M412740200 (2005). 82 Rayahin, J. E., Buhrman, J. S., Zhang, Y., Koh, T. J. Gemeinhart, R. A. High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater Sci Eng 1, 481-493, doi:10.1021/acsbiomaterials.5b00181 (2015). 83 Libby, P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 65, S140-146 (2007). 84 R J Bunn, G. B., C Connelly, G Li, D Marsh. INFLAMMATION – A DOUBLE EDGED SWORD IN HIGH-ENERGY FRACTURES? Orthopaedic Proceedings 87-B, 265-266 (2005). 85 Ricciotti, E. FitzGerald, G. A. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31, 986-1000, doi:10.1161/ATVBAHA.110.207449 (2011). 86 Hawkey, C. J. COX-1 and COX-2 inhibitors. Best Pract Res Clin Gastroenterol 15, 801-820, doi:10.1053/bega.2001.0236 (2001). 87 Zeng, Y. P. et al. Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-kappaB and MAPKs in RANKL-induced RAW264.7 cells. Mol Med Rep 14, 1957-1962, doi:10.3892/mmr.2016.5456 (2016). 88 Du, M., Pan, W., Duan, X., Yang, P. Ge, S. Lower dosage of aspirin promotes cell growth and osteogenic differentiation in murine bone marrow stromal cells. J Dent Sci 11, 315-322, doi:10.1016/j.jds.2016.03.009 (2016). 89 Nagy, E. et al. Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis. Peerj 5, doi:ARTN e3185 10.7717/peerj.3185 (2017). 90 Lavernia, C. J., Contreras, J. S., Villa, J. M. Rossi, M. D. Celecoxib and Heterotopic Bone Formation After Total Hip Arthroplasty. J Arthroplasty 29, 390-392, doi:10.1016/j.arth.2013.06.039 (2014). 91 Boursinos, L. A., Karachalios, T., Poultsides, L. Malizos, K. N. Do steroids, conventional non-steroidal anti-inflammatory drugs and selective Cox-2 inhibitors adversely affect fracture healing? J Musculoskel Neuron 9, 44-52 (2009). 92 Jeffcoach, D. R. et al. Nonsteroidal anti-inflammatory drugs' impact on nonunion and infection rates in long-bone fractures. J Trauma Acute Care Surg 76, 779-783, doi:10.1097/TA.0b013e3182aafe0d (2014). 93 Arulselvan, P. et al. Role of Antioxidants and Natural Products in Inflammation. Oxid Med Cell Longev 2016, 5276130, doi:10.1155/2016/5276130 (2016). 94 Schieber, M. Chandel, N. S. ROS function in redox signaling and oxidative stress. Curr Biol 24, R453-462, doi:10.1016/j.cub.2014.03.034 (2014). 95 Sheweita, S. A. Khoshhal, K. I. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab 8, 519-525 (2007). 96 Roper, P. M., Abbasnia, P., Vuchkovska, A., Natoli, R. M. Callaci, J. J. Alcohol-related deficient fracture healing is associated with activation of FoxO transcription factors in mice. J Orthop Res 34, 2106-2115, doi:10.1002/jor.23235 (2016). 97 Taylor, F. et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev, CD004816, doi:10.1002/14651858.CD004816.pub5 (2013). 98 Huang, W. C. et al. The Effect of Intensified Low Density Lipoprotein Cholesterol Reduction on Recurrent Myocardial Infarction and Cardiovascular Mortality. Acta Cardiol Sin 29, 404-412 (2013). 99 Odden, M. C. et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 years or older in the United States. Ann Intern Med 162, 533-541, doi:10.7326/M14-1430 (2015). 100 Shah, S. R., Werlang, C. A., Kasper, F. K. Mikos, A. G. Novel applications of statins for bone regeneration. Natl Sci Rev 2, 85-99, doi:10.1093/nsr/nwu028 (2015). 101 Abeles, A. M. Pillinger, M. H. Statins as antiinflammatory and immunomodulatory agents - A future in rheumatologic therapy? Arthritis Rheum-Us 54, 393-407, doi:10.1002/art.21521 (2006). 102 Dulak, J. Jozkowicz, A. Anti-angiogenic and anti-inflammatory effects of statins: Relevance to anti-cancer therapy. Curr Cancer Drug Tar 5, 579-594, doi:Doi 10.2174/156800905774932824 (2005). 103 Diamantis, E., Kyriakos, G., Quiles-Sanchez, L. V., Farmaki, P. Troupis, T. The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature. Curr Cardiol Rev 13, 209-216, doi:10.2174/1573403x13666170426104611 (2017). 104 Shah, S. R., Werlang, C. A., Kasper, F. K. Mikos, A. G. Novel applications of statins for bone regeneration. National Science Review 2, 85-99, doi:10.1093/nsr/nwu028 (2015). 105 Soulaidopoulos, S., Nikiphorou, E., Dimitroulas, T. Kitas, G. D. The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis. Front Med-Lausanne 5, doi:ARTN 24 10.3389/fmed.2018.00024 (2018). 106 Park, J. B. The use of simvastatin in bone regeneration. Med Oral Patol Oral 14, E485-E488 (2009). 107 Papadimitriou, K., Karkavelas, G., Vouros, I., Kessopoulou, E. Konstantinidis, A. Effects of local application of simvastatin on bone regeneration in femoral bone defects in rabbit. J Cranio Maxill Surg 43, 232-237, doi:10.1016/j.jcms.2014.11.011 (2015). 108 Degala, S. Bathija, N. A. Evaluation of the Efficacy of Simvastatin in Bone Regeneration after Surgical Removal of Bilaterally Impacted Third Molars-A Split-Mouth Randomized Clinical Trial. J Oral Maxil Surg 76, 1847-1858, doi:10.1016/j.joms.2018.04.035 (2018). 109 Tuomisto, T. T. et al. Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2. Cardiovasc Res 78, 175-184, doi:10.1093/cvr/cvn007 (2008). 110 Manni, G. et al. Statins regulates inflammatory macrophage phenotype through the activation of AhR. Journal of Immunology 200 (2018). 111 Wu, F. et al. Simvastatin alters M1/M2 polarization of murine BV2 microglia via Notch signaling. Journal of Neuroimmunology 316, 56-64, doi:10.1016/j.jneuroim.2017.12.010 (2018). 112 Tsikas, D. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci 851, 51-70, doi:10.1016/j.jchromb.2006.07.054 (2007). 113 Eruslanov, E. Kusmartsev, S. Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol 594, 57-72, doi:10.1007/978-1-60761-411-1_4 (2010). 114 Yen, M. L., Hsu, P. N., Liao, H. J., Lee, B. H. Tsai, H. F. TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation. PLoS One 7, e38048, doi:10.1371/journal.pone.0038048 (2012). 115 Lee, Y. D. et al. Caveolin-1 regulates osteoclastogenesis and bone metabolism in a sex-dependent manner. J Biol Chem 290, 6522-6530, doi:10.1074/jbc.M114.598581 (2015). 116 Lee, D. J. et al. Dopaminergic effects on in vitro osteogenesis. Bone Res 3, 15020, doi:10.1038/boneres.2015.20 (2015). 117 Thacker, G. et al. Skp2 inhibits osteogenesis by promoting ubiquitin-proteasome degradation of Runx2. Biochim Biophys Acta 1863, 510-519, doi:10.1016/j.bbamcr.2016.01.010 (2016). 118 Zhang, Y., Kong, N., Zhang, Y., Yang, W. Yan, F. Size-dependent Effects of Gold Nanoparticles on Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells. Theranostics 7, 1214-1224, doi:10.7150/thno.17252 (2017). 119 Salgueiro-Pagadigorria, C. L., Kelmer-Bracht, A. M., Bracht, A. Ishii-Iwamoto, E. L. Naproxen affects Ca(2+) fluxes in mitochondria, microsomes and plasma membrane vesicles. Chem Biol Interact 147, 49-63 (2004). 120 Davis, M. J. et al. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. MBio 4, e00264-00213, doi:10.1128/mBio.00264-13 (2013). 121 Robitaille, L. et al. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism 58, 263-269, doi:10.1016/j.metabol.2008.09.023 (2009). 122 Kimmel, D. B., Coble, T. Lane, N. Long-term effect of naproxen on cancellous bone in ovariectomized rats. Bone 13, 167-172 (1992). 123 Lee, N. K. et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106, 852-859, doi:10.1182/blood-2004-09-3662 (2005). 124 Cao, J. J. Picklo, M. J. N-Acetylcysteine Supplementation Decreases Osteoclast Differentiation and Increases Bone Mass in Mice Fed a High-Fat Diet. J Nutr 144, 289-296, doi:10.3945/jn.113.185397 (2014). 125 Abukawa, H. et al. Effect of ibuprofen on osteoblast differentiation of porcine bone marrow-derived progenitor cells. J Oral Maxillofac Surg 67, 2412-2417, doi:10.1016/j.joms.2009.05.434 (2009). 126 Salem, O. et al. Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules. Arthritis Res Ther 16, R152, doi:10.1186/ar4614 (2014). 127 Du, M., Pan, W., Yang, P. Ge, S. [Effect of aspirin on cell biological activities in murine bone marrow stromal cells]. Zhonghua Kou Qiang Yi Xue Za Zhi 51, 160-165, doi:10.3760/cma.j.issn.1002-0098.2016.03.007 (2016). 128 Elsoe, R., Ostgaard, S. E. Larsen, P. Population-based epidemiology of 9767 ankle fractures. Foot Ankle Surg 24, 34-39, doi:10.1016/j.fas.2016.11.002 (2018). 129 Allen, H. L., Wase, A. Bear, W. T. Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand 51, 595-600, doi:10.3109/17453678008990848 (1980). 130 Jameson, S. S. et al. Venous thromboembolic events following foot and ankle surgery in the English National Health Service. J Bone Joint Surg Br 93, 490-497, doi:10.1302/0301-620X.93B4.25731 (2011). 131 Capogna, B. M. Egol, K. A. Treatment of Nonunions After Malleolar Fractures. Foot Ankle Clin 21, 49-62, doi:10.1016/j.fcl.2015.09.004 (2016). 132 Lack, W. D. et al. Effect of aspirin on bone healing in a rabbit ulnar osteotomy model. J Bone Joint Surg Am 95, 488-496, doi:10.2106/JBJS.L.00462 (2013). 133 Zhang, X. P. et al. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 109, 1405-1415, doi:10.1172/Jci200215681 (2002). 134 Wu, L. et al. Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-kappaB and NFATc1 activation. Stem Cell Res Ther 10, 375, doi:10.1186/s13287-019-1500-x (2019). 135 Xie, Y. et al. Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration. Cell Biosci 9, 103, doi:10.1186/s13578-019-0369-9 (2019). 136 Hunter, A. M. et al. Postoperative aspirin use and its effect on bone healing in the treatment of ankle fractures. Injury 51, 554-558, doi:10.1016/j.injury.2019.11.039 (2020). 137 Du, M., Pan, W., Duan, X. Q., Yang, P. S. Ge, S. H. Lower dosage of aspirin promotes cell growth and osteogenic differentiation in murine bone marrow stromal cells. J Dent Sci 11, 315-322, doi:10.1016/j.jds.2016.03.009 (2016). 138 Zimmermann, P. Curtis, N. The effect of aspirin on antibiotic susceptibility. Expert Opin Ther Targets 22, 967-972, doi:10.1080/14728222.2018.1527314 (2018). 139 in Drugs and Lactation Database (LactMed) (2006). 140 Myers, L. K. et al. The isozyme-specific effects of cyclooxygenase-deficiency on bone in mice. Bone 39, 1048-1052, doi:10.1016/j.bone.2006.05.015 (2006). 141 Xu, M. S. et al. Do cyclooxygenase-2 knockout mice have primary hyperparathyroidism? Endocrinology 146, 1843-1853, doi:10.1210/en.2004-0734 (2005). 142 Loi, F. et al. The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. Stem Cell Research Therapy 7, doi:ARTN 15 10.1186/s13287-016-0276-5 (2016). 143 Schlundt, C. et al. Macrophages in bone fracture healing: Their essential role in endochondral ossification. Bone 106, 78-89, doi:10.1016/j.bone.2015.10.019 (2018). 144 Van den Bossche, J. et al. Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages. Cell Reports 17, 684-696, doi:10.1016/j.celrep.2016.09.008 (2016). 145 Oryan, A., Kamali, A. Moshiri, A. Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions. J Control Release 215, 12-24, doi:10.1016/j.jconrel.2015.07.022 (2015). 146 Moshiri, A., Shahrezaee, M., Shekarchi, B., Oryan, A. Azma, K. Three-Dimensional Porous Gelapin-Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits. Calcified Tissue Int 96, 552-564, doi:10.1007/s00223-015-9981-9 (2015). 147 Oryan, A., Alidadi, S., Moshiri, A. Maffulli, N. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res 9, 18, doi:10.1186/1749-799X-9-18 (2014). 148 Moon, H. J. et al. Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species. Exp Mol Med 43, 605-612, doi:10.3858/emm.2011.43.11.067 (2011). 149 Chung, Y. S., Lee, M. D., Lee, S. K., Kim, H. M. Fitzpatrick, L. A. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocr Metab 85, 1137-1142, doi:DOI 10.1210/jcem.85.3.6476 (2000). 150 Wu, F. et al. Simvastatin alters M1/M2 polarization of murine BV2 microglia via Notch signaling. J Neuroimmunol 316, 56-64, doi:10.1016/j.jneuroim.2017.12.010 (2018). 151 Yan, Q. et al. Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics. J Biomed Mater Res A 103, 3580-3589, doi:10.1002/jbm.a.35499 (2015). 152 Tao, Z. S. et al. The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats. Injury 46, 2164-2169, doi:10.1016/j.injury.2015.08.034 (2015). 153 Li, X. F. et al. Effects of Simvastatin and Combination of Simvastatin and Nylestriol on Bone Metabolism in Ovariectomized Rats. Am J Ther 23, e1630-e1636, doi:10.1097/MJT.0000000000000271 (2016). 154 Tan, J. et al. Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model. Med Sci Monit 21, 1428-1439, doi:10.12659/MSM.892247 (2015). 155 Issa, J. P. et al. The effect of simvastatin treatment on bone repair of femoral fracture in animal model. Growth Factors 33, 139-148, doi:10.3109/08977194.2015.1011270 (2015). 156 Yuan, F., Quan, L. D., Cui, L., Goldring, S. R. Wang, D. Development of macromolecular prodrug for rheumatoid arthritis. Adv Drug Deliver Rev 64, 1205-1219, doi:10.1016/j.addr.2012.03.006 (2012). 157 Jia, Z. et al. Simvastatin prodrug micelles target fracture and improve healing. Journal of Controlled Release 200, 23-34, doi:10.1016/j.jconrel.2014.12.028 (2015). 158 Danhier, F. et al. PLGA-based nanoparticles: An overview of biomedical applications. Journal of Controlled Release 161, 505-522, doi:10.1016/j.jconrel.2012.01.043 (2012). 159 Mirakabad, F. S. T. et al. PLGA-Based Nanoparticles as Cancer Drug Delivery Systems. Asian Pac J Cancer P 15, 517-535, doi:10.7314/Apjcp.2014.15.2.517 (2014). 160 Riffault, M., Six, J. L., Netter, P., Gillet, P. Grossin, L. PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies. Pharm Res-Dordr 32, 3886-3898, doi:10.1007/s11095-015-1748-5 (2015). 161 Tai, I. C., Fu, Y. C., Wang, C. K., Chang, J. K. Ho, M. L. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair. Int J Nanomed 8, 3895-3904, doi:10.2147/Ijn.S48694 (2013). 162 Zhai, P. S. et al. The application of hyaluronic acid in bone regeneration. Int J Biol Macromol 151, 1224-1239, doi:10.1016/j.ijbiomac.2019.10.169 (2020). 163 Gwon, K., Kim, E. Tae, G. Heparin-hyaluronic acid hydrogel in support of cellular activities of 3D encapsulated adipose derived stem cells. Acta Biomaterialia 49, 284-295, doi:10.1016/j.actbio.2016.12.001 (2017). 164 Collins, M. N. Birkinshaw, C. Comparison of the effectiveness of four different crosslinking agents with hyaluronic acid hydrogel films for tisslue-culture applications. J Appl Polym Sci 104, 3183-3191, doi:10.1002/app.25993 (2007). 165 Zhang, C. et al. Photopolymerizable thiol-acrylate maleiated hyaluronic acid/thiol-terminated poly(ethylene glycol) hydrogels as potential in-situ formable scaffolds. Int J Biol Macromol 119, 270-277, doi:10.1016/j.ijbiomac.2018.07.153 (2018). 166 Tokatlian, T., Cam, C., Siegman, S. N., Lei, Y. G. Segura, T. Design and characterization of microporous hyaluronic acid hydrogels for in vitro gene transfer to mMSCs. Acta Biomaterialia 8, 3921-3931, doi:10.1016/j.actbio.2012.07.014 (2012). 167 Martinez-Sanz, E. et al. Bone reservoir: Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation. Journal of Controlled Release 152, 232-240, doi:10.1016/j.jconrel.2011.02.003 (2011). 168 Silva, C. R. et al. Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration. Acta Biomaterialia 77, 155-171, doi:10.1016/j.actbio.2018.07.035 (2018). 169 Amini, A. R., Laurencin, C. T. Nukavarapu, S. P. Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40, 363-408, doi:10.1615/critrevbiomedeng.v40.i5.10 (2012). 170 Nath, S. D., Linh, N. T. B., Sadiasa, A. Lee, B. T. Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP porous spongy scaffold as a controlled drug delivery system for bone tissue regeneration. J Biomater Appl 28, 1151-1163, doi:10.1177/0885328213499272 (2014). 171 Alfonso-Garcia, A. et al. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy. J Biomed Opt 21, doi:Artn 046005 10.1117/1.Jbo.21.4.046005 (2016). 172 Galvan-Pena, S. O'Neill, L. A. Metabolic reprograming in macrophage polarization. Front Immunol 5, 420, doi:10.3389/fimmu.2014.00420 (2014). 173 Alfonso-Garcia, A. et al. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy. J Biomed Opt 21, 46005, doi:10.1117/1.JBO.21.4.046005 (2016). 174 Rayahin, J. E., Buhrman, J. S., Zhang, Y., Koh, T. J. Gemeinhart, R. A. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16189 | - |
| dc.description.abstract | 根據中華民國骨質疏鬆症學會的統計數字，台灣民眾髖關節骨折發生率在國際間名列前茅。而目前臨床醫學並無針對骨折癒合修復的專屬用藥，因此本研究的目標是開發生物相容性的奈米粒子促進骨折的修復速度，加速病患斷骨的癒合，減低病患生理、心理的壓力和經濟負擔。針對改善骨折患處局部的微環境，以加速骨折癒合。本研究的策略包括：（1）緩解骨折初期產生之急性發炎反應。（2）調節骨折微環境中巨噬細胞的極化。本研究利用兩種劑型：（1）生物可降解的奈米載體（PLGA）包覆抗發炎藥物，用以緩解發炎；（2）PLGA包覆免疫調節藥物，在骨折微環境增加M2巨噬細胞數量達到加速癒合目的。同時，在奈米粒子外層修飾玻尿酸，增加極化巨噬細胞效率。抗炎藥物選擇上，設計篩藥平台用篩選適合骨折修復的抗炎藥物，條件包括了LPS處理RAW264.7細胞株模擬發炎環境，加入臨床使用的抗發炎藥物進行測試，DCFDA偵測自由基、Griess試劑檢測一氧化氮等發炎指標的產物來確認藥物的效力，同時也利用MTT測試細胞存活率確認有效劑量。使用alizarin rad s染色，偵測抗發炎藥物是否影響造骨細胞的分化，並使用TRAP染色，偵測抗發炎藥物是否影響蝕骨細胞的分化能力，經由篩藥平台的篩選，阿斯匹靈是適合骨折使用之抗炎藥物。本研究亦使用巨噬細胞株，經由QPCR、Flow cytometry等技術建立並鑑定辛伐他汀成功介導M2-like巨噬細胞數量，並且於巨噬細胞轉換的過程中成功觀察到造骨細胞分化。接著，將辛伐他汀進行奈米劑型合成，該載體經證實有效介導M2-like巨噬細胞數量進而促進造骨細胞活化。本研究成功藉由核磁共振成像觀察到本研究開發的奈米載體可使骨傷位置呈現消炎狀態，並開創雙光子共軛焦顯微鏡即時觀察動物骨質上巨噬細胞極化狀態。綜合以上，本研究之奈米劑型極具潛力應用於促骨癒合。 | zh_TW |
| dc.description.abstract | According to statistics released by the Taiwanese Osteoporosis Association, the incidence of hip bone fracture in Taiwan ranks at top in Asia. Traditional repair of fracture remains to be anatomic reduction and rigid internal fixation. Bone fracture may be costly, in terms of direct medical costs and lost productivity. Up to now, there is no clinical medication available that is specifically designed for fractures. Hence, in this study is to develop bio-compatible nanoparticles to promote the bone repair, leading to the acceleration in the rehabilitation of the patients, and shortening of the recovery time. One of our strategies in promoting bone fracture is to improve the inflammatory microenvironment of fracture site. The other strategy is related to the manipulation of macrophages (toward M2-like) involving in fracture repair. We herein design two nano-formulations for achieving our specific aims. The utilization of bio-degradable PLGA nanoparticles, carrying anti-inflammatory drugs is to relieve inflammation. While immunomodulatory drugs were encapsulated in hyaluronic acid-modified PLGA nanoparticles, the switch of M0 macrophage to M2-like macrophage become feasible. Recently, we have proved that nanoformulations can improve bone fracture healing via in vitro/in vivo experiment. This experimental evidence can make our nanoformulations as potential medicine for bone fracture in clinical. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T18:04:23Z (GMT). No. of bitstreams: 1 U0001-0402202112340500.pdf: 5413798 bytes, checksum: 70ae4725ffd959fb6976226efe77e768 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 目錄 口試委員審定書 I 謝誌 II 中文摘要 III Abstract IV 縮寫表 V 第一章 緒論 1 1.1 前言 1 1.2 骨骼 1 1.2.1 骨骼構造 1 1.2.2 骨折類型 3 1.2.3 骨折修復階段 5 1.2.4 骨折治療 8 1.2.5 造骨細胞（Osteoblast）和骨細胞（Osteocyte） 9 1.2.6 蝕骨細胞（Osteoclast） 10 1.3 巨噬細胞在骨折修復環境的角色 11 1.4 奈米技術在骨再生的應用 13 1.4.1 聚乳酸聚乙醇酸（PLGA）奈米載體 14 1.5 玻尿酸（Hyaluronic acid） 15 1.6 抗發炎藥物（Anti-inflammation drugs） 16 1.6.1 布洛芬（Ibuprofen） 17 1.6.2 萘普生（Naproxen） 17 1.6.3 阿斯匹靈（Aspirin） 18 1.6.4 美洛昔康（Meloxicam） 18 1.6.5 塞來昔布（Celecoxib） 19 1.6.6 依托考昔（Etoricoxib） 19 1.7 抗氧化藥物（Anti-oxidant drugs） 20 1.7.1 抗壞血酸（Ascorbic acid） 21 1.7.2 乙醯半胱氨酸（N-acetyl-cysteine；NAC） 21 1.8 他汀類藥物 （Stain drugs） 22 1.8.1 辛伐他汀（Simvastatin） 23 第二章 研究目的與策略 24 第三章 材料與方法 27 3.1 細胞培養及細胞株 (Cell lines and Cell culture) 27 3.2 細胞mRNA萃取與反轉錄 (mRNA extraction and Reverse Transcription) 28 3.2.1 mRNA萃取 28 3.2.2 mRNA定量 28 3.2.3 反轉錄 29 3.3 聚合酶鏈鎖反應 (Polymerase Chain Reaction, PCR) 29 3.4 即時定量聚合酶鏈鎖反應 (Real-time PCR；Quantitative PCR；QPCR) 31 3.5 西方墨點法 （Western blotting assay） 31 3.5.1 蛋白質萃取液之取得 31 3.5.2 蛋白質定量 32 3.5.3 蛋白質電泳凝膠（SDS-PAGE）之配置 32 3.5.4 SDS-PAGE蛋白質膠體電泳 33 3.5.5 蛋白質樣本轉印 33 3.5.6 免疫墨點法 (Immuno-blotting) 34 3.6 細胞存活率測定（MTT cell viability assay） 34 3.7 台盼藍染色（Trypan blue staining） 35 3.8 細胞分化 （Cell differentiation） 35 3.9 茜紅素S染色（Alizarin Rad S Staining assay；ARS） 36 3.10 抗酒石酸酸性磷酸酶染色（Tartrate-resistant acid phosphatase stain；TRAP） 37 3.11 一氧化氮累積量偵測（Griess Assay） 38 3.12 細胞內自由基偵測（Intracellular reactive oxygen species；ROS） 38 3.13 免疫螢光染色（Immunofluorescence assay；IFA） 39 3.14 流式細胞儀分析（Flow cytometric analysis） 40 3.15 In vitro雙光子共軛焦顯微鏡（Two-Photon Confocal Microscopy）觀察 40 3.16 脂質PLGA複合奈米粒子合成（Lipid-PLGA） 40 3.17 玻尿酸透析（Dialysis） 41 3.18 樣品冷凍乾燥（Freeze drying；Lyophilisation） 42 3.19 玻尿酸修飾脂質PLGA複合奈米粒子（HA-Lipid-PLGA） 42 3.20 動態光散射粒徑分析及電位分析（Dynamic Light Scattering/Zeta Potential Analyzer） 43 3.21 紫外光/可見光光譜儀（UV-VIS）定量 43 3.22 奈米粒子釋放曲線（Release Profile）測定 44 3.23 動物骨傷模型建立 45 3.24 建立分辯率核磁共振特殊影像 45 3.25 In vivo雙光子共軛焦顯微鏡（Two-Photon Confocal Microscopy）觀察 46 第四章 現有結果與討論 47 4.1 建立蝕骨細胞及造骨細胞分化和鑑定平台 47 4.2 確認各種抗發炎、抗氧化候選藥物對單核球細胞的存活率影響 52 4.3 確認各種抗發炎、抗氧化候選藥物對抗氧化指標之有效劑量 54 4.4 建立巨噬細胞極化以及鑑定系統 57 4.5 確認各種抗發炎候選藥物是否具有促M1至M2極化能力 60 4.6 確認各種抗發炎候選藥物是否具有抑制蝕骨細胞分化能力 62 4.7 確認各種抗發炎候選藥物是否具有抑制造骨細胞分化能力 65 4.8 極化巨噬細胞型態對造骨細胞之影響 69 4.9 辛伐他汀對巨噬細胞極化狀態之影響 71 4.10 包覆辛伐他汀之脂質PLGA複合奈米粒子之合成結果與型態鑑定 78 4.11 包覆辛伐他汀之脂質PLGA複合奈米粒子修飾玻尿酸之合成結果與型態鑑定 81 4.12 奈米粒子藥物釋放曲線（Release profile） 85 4.13 奈米粒子包覆辛伐他汀對巨噬細胞極化狀態之影響 87 4.14 奈米粒子包覆辛伐他汀極化巨噬細胞對造骨細胞之影響 90 4.15 特殊MRI影像對骨傷動物微環境檢測 93 4.16 雙光子共軛焦顯微鏡對骨傷動物模型M1/M2巨噬細胞影像測試 95 第五章 總論與未來展望 99 第六章 參考文獻 104 | |
| dc.language.iso | zh-TW | |
| dc.subject | 骨折癒合 | zh_TW |
| dc.subject | 雙光子共軛焦顯微鏡 | zh_TW |
| dc.subject | 核磁共振成像 | zh_TW |
| dc.subject | 抗氧化 | zh_TW |
| dc.subject | 抗發炎 | zh_TW |
| dc.subject | M2型態巨噬細胞 | zh_TW |
| dc.subject | M1型態巨噬細胞 | zh_TW |
| dc.subject | 奈米藥物傳輸系統 | zh_TW |
| dc.subject | anti-inflammatory | en |
| dc.subject | anti-oxidative stress | en |
| dc.subject | MRI | en |
| dc.subject | M2 type macrophage | en |
| dc.subject | Two-photon microscopy | en |
| dc.subject | M1 type macrophage | en |
| dc.subject | bone fracture healing | en |
| dc.subject | nanodrug delivery system | en |
| dc.title | 發展具生物可利用性的奈米粒子以促進骨折癒合 | zh_TW |
| dc.title | Development of bio-applicable nanoparticles for the promotion of fracture healing | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 109-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 周必泰(Pi-Tai Chou),徐士蘭(Shih-Lan Hsu),吳立真(Li-Chen Wu),曾崇育(Chugn-Yuh Tseng),楊家銘(Chia-Min Yang) | |
| dc.subject.keyword | 骨折癒合,奈米藥物傳輸系統,M1型態巨噬細胞,M2型態巨噬細胞,抗發炎,抗氧化,核磁共振成像,雙光子共軛焦顯微鏡, | zh_TW |
| dc.subject.keyword | bone fracture healing,nanodrug delivery system,M1 type macrophage,M2 type macrophage,anti-inflammatory,anti-oxidative stress,MRI,Two-photon microscopy, | en |
| dc.relation.page | 118 | |
| dc.identifier.doi | 10.6342/NTU202100504 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-02-04 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-0402202112340500.pdf 未授權公開取用 | 5.29 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。