本研究使用羥丙基纖維素和明膠作為支架基材並與骨母細胞進行培養，並藉由臭氧的強氧化性使支架表面產生過氧化物，透過氧化還原等方式將柚皮苷固定於支架的表面。柚皮苷為天然黃酮類，是一種HMG-CoA之抑制劑，過去文獻有提到柚皮苷能促進骨細胞的行為表現，如增生、分化等特性，但過高的濃度則會產生細胞毒性。本研究利用臭氧活化的方式固定柚皮苷於支架上，改善以往文獻中使用柚皮苷時釋放過快，短時間內濃度過高的問題。
本實驗藉由紅外線光譜(FTIR)、膨潤性測試以及SEM分析支架改質後的特性，由結果可證明柚皮苷成功接枝於材料表面，且支架經改質後的結構以及親疏水性無明顯改變。而釋放實驗的結果，則可證實本研究的改質接枝程序在釋放含量與時間上優於單純物理吸附的方式，且透過此緩慢地釋放程序，可以良好的控制培養液中柚皮苷的濃度，達到一長效型的釋放模式。
由細胞實驗的結果，支架在經臭氧活化固定柚皮苷後可大幅增進其細胞親和性來促進細胞的貼附以及活性。此外，柚皮苷也促進了骨細胞的分化，初期骨分化指標的鹼性磷酸酶(alkaline phosphatase, ALP)以及後期的骨鈣素(osteocalcin, OCN)含量，在經改質後的支架上其分泌表現提高了近乎一倍。
由SEM以及螢光染色結果可發現支架在固定柚皮苷後，其細胞貼附的數量以及細胞骨架貼附面積如層狀的lamellipodia皆有明顯的增長，此可證明材料在經改質接枝柚皮苷後其細胞親合度大幅的上升。利用螢光染色以及不同環境培養的結果，可證實本研究所使用的支架為三維支架，可提供細胞於支架內部成長形成三維立體生長模式。此外透過動態系統的培養，亦可得知本研究支架在類似體內環境與骨母細胞培養時可擁有更佳的細胞活性表現。

In this research, we used the hydroxypropyl cellulose and gelatin as the scaffold with the immobilization of naringin by ozone treatment. The hydroxypropyl cellulose and gelatin in the ozone treatment were optimized.
The amounts of peroxides produced by ozone treatment were quantified and optimized by the DPPH assay. The efficiency of peroxide generation on hydroxypropyl cellulose was greatly higher than those on the other polymers. The finding supported that the ozone activation process was efficient on hydroxypropyl cellulose. The scaffolds with immobilized naringin were characterized by FTIR, swelling test and SEM. The results showed that naringin was successfully grafted onto scaffold. The topography and hydrophilic did not change after surface modification, indicating that grafted naringin would be the only factor which may influence cultured osteoblastic cells. Besides, the in vitro release of naringin from scaffold was also tested. The results reveal that the immobilized naringin by ozone oxidation was slowly released and the released amount and time were better than the physical adsorption.
The results from cell culture indicated that the cell viability, attachment, proliferation and osteogenic differentiation were promoted by the immobilized naringin on scaffold. Compared with two dimensional culture, the osteoblastic cells cultured with 3 dimensional hydroxypropyl cellulose and gelatin scaffolds presented higher cell affinity and activity.

1. Machida, Y. and T. Nagai, Application of hydroxypropyl cellulose to peroral controlled release dosage forms. Chemical and Pharmaceutical Bulletin, 1978. 26(6): p. 1652-1658.
2. Vandelli, MA, Leo, F. E, and B. F, Drug release from perforated matrices containing hydroxypropylcellulose. International journal of pharmaceutics, 1998. 171(2): p. 165-175.
3. Hoo, S.P., Q.L. Loh, Z. Yue, J. Fu, T.T. Tan, C. Choong, and P.P. Chan, Preparation of a soft and interconnected macroporous hydroxypropyl cellulose methacrylate scaffold for adipose tissue engineering. Journal of Materials Chemistry B, 2013. 1(24): p. 3107-3117.
4. Kawai, K., S. Suzuki, Y. Tabata, Y. Ikada, and Y. Nishimura, Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis. Biomaterials, 2000. 21(5): p. 489-499.
5. Choy, Y.B., F. Cheng, H. Choi, and K.K. Kim, Monodisperse gelatin microspheres as a drug delivery vehicle: release profile and effect of crosslinking density. Macromolecular bioscience, 2008. 8(8): p. 758-765.
6. Tabata, Y. and Y. Ikada, Protein release from gelatin matrices. Advanced drug delivery reviews, 1998. 31(3): p. 287-301.
7. Yue, Z., F. Wen, S. Gao, M.Y. Ang, P.K. Pallathadka, L. Liu, and H. Yu, Preparation of three-dimensional interconnected macroporous cellulosic hydrogels for soft tissue engineering. Biomaterials, 2010. 31(32): p. 8141-8152.
8. Lin, J.Y., W.J. Lin, W.H. Hong, W.C. Hung, S.H. Nowotarski, S.M. Gouveia, I. Cristo, and K.-h. Lin, Morphology and organization of tissue cells in 3D microenvironment of monodisperse foam scaffolds. Soft Matter, 2011. 7(21): p. 10010-10016.
9. Wong, R.W.K. and A.B.M. Rabie, Bone induction using hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Hong Kong Dental Journal, 2007.8(5): p.52
10. Li, L., Z. Zeng, and G. Cai, Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1. Phytomedicine, 2011. 18(11): p. 985-989.
11. Dai, K.R., S.G. Yan, W.Q. Yan, D.Q. Chen, and Z.W. Xu, Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. European journal of pharmacology, 2009. 607(1): p. 1-5.
12. Wu, J.B., Y.C. Fong, H.Y. Tsai, Y.F. Chen, M. Tsuzuki, and C.H. Tang, Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts. European journal of pharmacology, 2008. 588(2): p. 333-341.
13. Galon, J., W.H. Fridman, and F. Pagès, The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer research, 2007. 67(5): p. 1883-1886.
14. Heams, T., Selection within organisms in the nineteenth century: Wilhelm Roux’s complex legacy. Progress in biophysics and molecular biology, 2012. 110(1): p. 24-33.
15. Harrison, R.G., Embryonic transplantation and development of the nervous system. The Anatomical Record, 1908. 2(9): p. 385-410.
16. Carrel, A. and R. Ingebrigtsen, The production of antibodies by tissues living outside of the organism. The Journal of experimental medicine, 1912. 15(3): p. 287.
17. Baker, B.M. and C.S. Chen, Deconstructing the third dimension–how 3D culture microenvironments alter cellular cues. J Cell Sci, 2012. 125(13): p. 3015-3024.
18. Chitcholtan, K., E. Asselin, S. Parent, P.H. Sykes, and J.J. Evans, Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Experimental cell research, 2013. 319(1): p. 75-87.
19. Chetty, A.S., V. Vargha, A. Maity, F.S. Moolman, C. Rossouw, R. Anandjiwala, L. Boguslavsky, D. Mancama, and W.W. Focke, Development of thermoresponsive poly (propylene-g-N-isopropylacrylamide) non-woven 3D scaffold for smart cell culture using oxyfluorination-assisted graft polymerisation. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013. 419: p. 37-45.
20. Liu, X., E.M. Weaver, and A.B. Hummon, Evaluation of therapeutics in three-dimensional cell culture systems by MALDI imaging mass spectrometry. Analytical chemistry, 2013. 85(13): p. 6295.
21. Benien, P. and A. Swami, 3D tumor models: history, advances and future perspectives. Future Oncology, 2014. 10(7): p. 1311-1327.
22. Kwapiszewska, K., A. Michalczuk, M. Rybka, R. Kwapiszewski, and Z. Brzózka, A microfluidic-based platform for tumour spheroid culture, monitoring and drug screening. Lab on a Chip, 2014. 14(12): p. 2096-2104.
23. Matsusaki, M., C.P. Case, and M. Akashi, Three-dimensional cell culture technique and pathophysiology. Advanced drug delivery reviews, 2014. 74(3): p. 95-103.
24. Lucas, C., C. Massart, J. Campion, B. Launois, and M. Nicol, Long-term culture of human pancreatic islets in an extracellular matrix: morphological and metabolic effects. Molecular and cellular endocrinology, 1993. 94(1): p. 9-20.
25. Koutsopoulos, S. and S. Zhang, Long-term three-dimensional neural tissue cultures in functionalized self-assembling peptide hydrogels, matrigel and collagen I. Acta biomaterialia, 2013. 9(2): p. 5162-5169.
26. Jaramillo, M., S.S. Singh, S. Velankar, P.N. Kumta, and I. Banerjee, Inducing endoderm differentiation by modulating mechanical properties of soft substrates. Journal of tissue engineering and regenerative medicine, 2015. 9(1): p. 1-12.
27. Gao, S., P. Zhao, C. Lin, Y. Sun, Y. Wang, Z. Zhou, D. Yang, X. Wang, H. Xu, and F. Zhou, Differentiation of human adipose-derived stem cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds. Tissue Engineering Part A, 2014. 20(7-8): p. 1271-1284.
28. Lien, S.M., L.Y. Ko, and T.J. Huang, Effect of pore size on ECM secretion and cell growth in gelatin scaffold for articular cartilage tissue engineering. Acta Biomaterialia, 2009. 5(2): p. 670-679.
29. Chong, E., T. Phan, I. Lim, Y. Zhang, B. Bay, S. Ramakrishna, and C. Lim, Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta biomaterialia, 2007. 3(3): p. 321-330.
30. Guido, S. and N. Grizzuti, Phase separation effects in the rheology of aqueous solutions of hydroxypropylcellulose. Rheologica acta, 1995. 34(2): p. 137-146.
31. Carotenuto, C. and N. Grizzuti, Thermoreversible gelation of hydroxypropylcellulose aqueous solutions. Rheologica acta, 2006. 45(4): p. 468-473.
32. Fukuyama, T. and Y. FUKASE, Effects of α-DT cement with hydroxypropyl cellulose on bone augmentation within a titanium cap in the rabbit calvarium. Dental materials journal, 2010. 29(2): p. 160-166.
33. Ockerman, H.W. and C.L. Hansen, Animal by-product processing & utilization. 1999.5(4): p. 46.
34. Tamada, Y. and Y. Ikada, Fibroblast growth on polymer surfaces and biosynthesis of collagen. Journal of Biomedical Materials Research Part A, 1994. 28(7): p. 783-789.
35. Van Wachem, P., A. Hogt, T. Beugeling, J. Feijen, A. Bantjes, J. Detmers, and W. Van Aken, Adhesion of cultured human endothelial cells onto methacrylate polymers with varying surface wettability and charge. Biomaterials, 1987. 8(5): p. 323-328.
36. Chan, C.M., Polymer surface modification and characterization. 1993.5(6): p. 68.
37. Garbassi, F., M. Morra, E. Occhiello, and F. Garbassi, Polymer surfaces: from physics to technology. 1998.13(4): p. 47.
38. El Din, H.M.N., M.F.A. Taleb, and A.W.M. El-Naggar, Metal sorption and swelling characters of acrylic acid and sodium alginate based hydrogels synthesized by gamma irradiation. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2008. 266(11): p. 2607-2613.
39. Hua, S. and A. Wang, Synthesis, characterization and swelling behaviors of sodium alginate-g-poly (acrylic acid)/sodium humate superabsorbent. Carbohydrate Polymers, 2009. 75(1): p. 79-84.
40. Kramer, P., Y. Yeh, and H. Yasuda, Low temperature plasma for the preparation of separation membranes. Journal of Membrane Science, 1989. 46(1): p. 1-28.
41. Wang, Y., J.H. Kim, K.H. Choo, Y.S. Lee, and C.H. Lee, Hydrophilic modification of polypropylene microfiltration membranes by ozone-induced graft polymerization. Journal of Membrane Science, 2000. 169(2): p. 269-276.
42. Tsai, C.C., Y. Chang, H.W. Sung, J.C. Hsu, and C.N. Chen, Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin): an in vitro study. Biomaterials, 2001. 22(6): p. 523-533.
43. Peeling, J., M.S. Jazzar, and D.T. Clark, An ESCA study of the surface ozonation of polystyrene film. Journal of Polymer Science: Polymer Chemistry Edition, 1982. 20(7): p. 1797-1805.
44. Karlsson, J. and P. Gatenholm, Solid-supported wettable hydrogels prepared by ozone induced grafting. Polymer, 1996. 37(19): p. 4251-4256.
45. Tu, C.Y., Y.L. Liu, K.R. Lee, and J.Y. Lai, Surface grafting polymerization and modification on poly (tetrafluoroethylene) films by means of ozone treatment. Polymer, 2005. 46(18): p. 6976-6985.
46. Dasgupta, S., Surface modification of polyolefins for hydrophilicity and bondability: Ozonization and grafting hydrophilic monomers on ozonized polyolefins. Journal of Applied Polymer Science, 1990. 41(1‐2): p. 233-248.
47. Chen, W.J., Analysis of Osteoinductivity and Cell-Material Interaction of Naringin-Chitosan Substrates Prepare by Ozone Treatment. 2014.2(3): p.69.
48. Alsheyab, M.A. and A.H. Muñoz, Comparative study of ozone and MnO2/O3 effects on the elimination of TOC and COD of raw water at the Valmayor station. Desalination, 2007. 207(1-3): p. 179-183.
49. Chen, L.C., Effects of factors and interacted factors on the optimal decolorization process of methyl orange by ozone. Water Research, 2000. 34(3): p. 974-982.
50. Yuan, Y., J. Zhang, F. Ai, J. Yuan, J. Zhou, J. Shen, and S. Lin, Surface modification of SPEU films by ozone induced graft copolymerization to improve hemocompatibility. Colloids and Surfaces B: Biointerfaces, 2003. 29(4): p. 247-256.
51. Park, J.C., Y.S. Hwang, J.E. Lee, K.D. Park, K. Matsumura, S.H. Hyon, and H. Suh, Type I atelocollagen grafting onto ozone‐treated polyurethane films: Cell attachment, proliferation, and collagen synthesis. Journal of Biomedical Materials Research Part A, 2000. 52(4): p. 669-677.
52. Lo, T.Y., The preparation and characterization of ozone modified PLLA scaffolds for osteoinduction. 2010.46(18): p.676.
53. Moad, G. and D.H. Solomon, The chemistry of radical polymerization. 2006.6(1): p.76: .
54. Chuchin, A.Y., Free radical reactions of polyarylenealkylenes and their hydroperoxides. Review. Polymer Science USSR, 1979. 21(7): p. 1579-1618.
55. O'Neill, T., Grafting of acrylic acid onto radiation‐peroxidized polypropylene film in the presence of ferrous ion. Journal of Polymer Science Part A‐1: Polymer Chemistry, 1972. 10(2): p. 569-580.
56. Matyjaszewski, K. and T.P. Davis, Handbook of radical polymerization. 2003.2(5): p. 56.
57. Fujimoto, K., Y. Takebayashi, H. Inoue, and Y. Ikada, Ozone‐induced graft polymerization onto polymer surface. Journal of Polymer Science Part A: Polymer Chemistry, 1993. 31(4): p. 1035-1043.
58. Roy, D., M. Semsarilar, J.T. Guthrie, and S. Perrier, Cellulose modification by polymer grafting: a review. Chemical Society Reviews, 2009. 38(7): p. 2046-2064.
59. Karlsson, J. and P. Gatenholm, Preparation and characterization of cellulose-supported HEMA hydrogels. Polymer, 1997. 38(18): p. 4727-4731.
60. Jeong, J.C., B.T. Lee, C.H. Yoon, H.M. Kim, and C.H. Kim, Effects of Drynariae rhizoma on the proliferation of human bone cells and the immunomodulatory activity. Pharmacological research, 2005. 51(2): p. 125-136.
61. Wong, R.W., B. Rabie, M. Bendeus, and U. Hägg, The effects of Rhizoma Curculiginis and Rhizoma Drynariae extracts on bones. Chinese medicine, 2007. 2(1): p. 13.
62. Chen, L.L., L.H. Lei, P.H. Ding, Q. Tang, and Y.M. Wu, Osteogenic effect of Drynariae rhizoma extracts and Naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Archives of oral biology, 2011. 56(12): p. 1655-1662.
63. Harborne, J.B. and C.A. Williams, Advances in flavonoid research since 1992. Phytochemistry, 2000. 55(6): p. 481-504.
64. Middleton, E., C. Kandaswami, and T.C. Theoharides, The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacological reviews, 2000. 52(4): p. 673-751.
65. Jagetia, G.C. and T.K. Reddy, Alleviation of iron induced oxidative stress by the grape fruit flavanone naringin in vitro. Chemico-biological interactions, 2011. 190(2): p. 121-128.
66. Gutteridge, J. and B. Halliwell, Free radicals and antioxidants in the year 2000: a historical look to the future. Annals of the New York Academy of Sciences, 2000. 899(1): p. 136-147.
67. Deng, W., X. Fang, and J. Wu, Flavonoids function as antioxidants: by scavenging reactive oxygen species or by chelating iron? Radiation Physics and Chemistry, 1997. 50(3): p. 271-276.
68. Bok, S.H., Y.W. Shin, K.H. Bae, T.S. Jeong, Y.K. Kwon, Y.B. Park, and M.S. Choi, Effects of naringin and lovastatin on plasma and hepatic lipids in high-fat and high-cholesterol fed rats. Nutrition Research, 2000. 20(7): p. 1007-1015.
69. Kim, H.J., G.T. Oh, Y.B. Park, M.K. Lee, H.J. Seo, and M.S. Choi, Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition. Life sciences, 2004. 74(13): p. 1621-1634.
70. Attia, S.M., Abatement by naringin of lomefloxacin-induced genomic instability in mice. Mutagenesis, 2008. 23(6): p. 515-521.
71. Jagetia, G.C. and T.K. Reddy, The grapefruit flavanone naringin protects against the radiation-induced genomic instability in the mice bone marrow: a micronucleus study. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2002. 519(1): p. 37-48.
72. Jagetia, G.C., V. Venkatesha, and T.K. Reddy, Naringin, a citrus flavonone, protects against radiation-induced chromosome damage in mouse bone marrow. Mutagenesis, 2003. 18(4): p. 337-343.
73. Russo, A., R. Acquaviva, A. Campisi, V. Sorrenti, C. Di Giacomo, G. Virgata, M. Barcellona, and A. Vanella, Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors. Cell biology and toxicology, 2000. 16(2): p. 91-98.
74. Park, S.H., E.K. Park, and D.-H. Kim, Passive cutaneous anaphylaxis-inhibitory activity of flavanones from Citrus unshiu and Poncirus trifoliata. Planta medica, 2005. 71(01): p. 24-27.
75. Tsui, V., R. Wong, and A.B.M. Rabie, The inhibitory effects of naringin on the growth of periodontal pathogens in vitro. Phytotherapy Research, 2008. 22(3): p. 401-406.
76. Peter, F., Mechanism-Based Inactivation of Human Liver Microsomal Cytochrome P-450 II IA4 by Gestodene. 1990.3(8): p.23.
77. Jeon, S.M., Y.B. Park, and M.S. Choi, Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clinical nutrition, 2004. 23(5): p. 1025-1034.
78. Le Marchand, L., S.P. Murphy, J.H. Hankin, L.R. Wilkens, and L.N. Kolonel, Intake of flavonoids and lung cancer. Journal of the National Cancer Institute, 2000. 92(2): p. 154-160.
79. Jung, U.J., M.K. Lee, K.S. Jeong, and M.S. Choi, The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. The Journal of nutrition, 2004. 134(10): p. 2499-2503.
80. Galati, E., M. Monforte, A. d’Aquino, N. Miceli, D. Di Mauro, and R. Sanogo, Effects of naringin on experimental ulcer in rats. Phytomedicine, 1998. 5(5): p. 361-366.
81. Kanno, S.I., A. Shouji, A. Tomizawa, T. Hiura, Y. Osanai, M. Ujibe, Y. Obara, N. Nakahata, and M. Ishikawa, Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages. Life sciences, 2006. 78(7): p. 673-681.
82. Pu, P., D.M. Gao, S. Mohamed, J. Chen, J. Zhang, X.Y. Zhou, N.J. Zhou, J. Xie, and H. Jiang, Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Archives of biochemistry and biophysics, 2012. 518(1): p. 61-70.
83. Singh, D., V. Chander, and K. Chopra, Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney. Toxicology, 2004. 201(1): p. 143-151.
84. Habauzit, V., S.M. Sacco, A. Gil, I, A. Trzeciakiewicz, C. Morand, D. Barron, S. Pinaud, E. Offord, and M.N. Horcajada, Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism. Bone, 2011. 49(5): p. 1108-1116.
85. Wong, R.W. and A.B.M. Rabie, Effect of naringin collagen graft on bone formation. Biomaterials, 2006. 27(9): p. 1824-1831.
86. Wong, R. and A. Rabie, Effect of naringin on bone cells. Journal of orthopaedic research, 2006. 24(11): p. 2045-2050.
87. Wang, E.A., V. Rosen, P. Cordes, R.M. Hewick, M.J. Kriz, D.P. Luxenberg, B.S. Sibley, and J.M. Wozney, Purification and characterization of other distinct bone-inducing factors. Proceedings of the National Academy of Sciences, 1988. 85(24): p. 9484-9488.
88. Riley, E.H., J.M. Lane, M.R. Urist, K.M. Lyons, and J.R. Lieberman, Bone morphogenetic protein-2: biology and applications. Clinical orthopaedics and related research, 1996. 324: p. 39-46.
89. Wong, R. and A. Rabie, Effect of Bio-Oss® Collagen and Collagen matrix on bone formation. The open biomedical engineering journal, 2010. 4(1): p.46.
90. Katagiri, T., A. Yamaguchi, M. Komaki, E. Abe, N. Takahashi, T. Ikeda, V. Rosen, J.M. Wozney, A. Fujisawa-Sehara, and T. Suda, Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. Journal of Cell Biology, 1994. 127(6): p. 1755-1766.
91. Boyle, W.J., W.S. Simonet, and D.L. Lacey, Osteoclast differentiation and activation. Nature, 2003. 423(6937): p. 337-342.
92. Ang, E.S., X. Yang, H. Chen, Q. Liu, M.H. Zheng, and J. Xu, Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL‐induced NF‐κB and ERK activation. FEBS letters, 2011. 585(17): p. 2755-2762.
93. YU, H.W., W.N. GU, N. LI, F. ZHANG, X.F. LIU, and H.M. WEI, Research Progress of Naringin [J]. Hubei Agricultural Sciences, 2011. 8: p. 005.
94. Pereira, R., N.E. Andrades, N. Paulino, A.C. Sawaya, M.N. Eberlin, M.C. Marcucci, G.M. Favero, E.M. Novak, and S.P. Bydlowski, Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity. Molecules, 2007. 12(7): p. 1352-1366.
95. Ji, Y., L. Wang, D.C. Watts, H. Qiu, T. You, F. Deng, and X. Wu, Controlled-release naringin nanoscaffold for osteoporotic bone healing. Dental Materials, 2014. 30(11): p. 1263-1273.
96. Beck, G.R., Inorganic phosphate as a signaling molecule in osteoblast differentiation. Journal of cellular biochemistry, 2003. 90(2): p. 234-243.
97. Stein, G.S., J.B. Lian, J.L. Stein, A.J. Van Wijnen, and M. Montecino, Transcriptional control of osteoblast growth and differentiation. Physiological reviews, 1996. 76(2): p. 593-629.
98. Ko, Y.G., Y.H. Kim, K.D. Park, H.J. Lee, W.K. Lee, H. Dal Park, S.H. Kim, G.S. Lee, and D.J. Ahn, Immobilization of poly (ethylene glycol) or its sulfonate onto polymer surfaces by ozone oxidation. Biomaterials, 2001. 22(15): p. 2115-2123.
99. Brondino, C., B. Boutevin, J.P. Parisi, and J. Schrynemackers, Adhesive properties onto galvanized steel plates of grafted poly (vinylidene fluoride) powders with phosphonated acrylates. Journal of applied polymer science, 1999. 72(5): p. 611-620.
100. Belgacem, M.N. and A. Gandini, The surface modification of cellulose fibres for use as reinforcing elements in composite materials. Composite Interfaces, 2005. 12(1-2): p. 41-75.
101. Lu, J., P. Askeland, and L.T. Drzal, Surface modification of microfibrillated cellulose for epoxy composite applications. Polymer, 2008. 49(5): p. 1285-1296.
102. Patel, D., J. Wu, P. Chan, S. Upreti, G. Turcotte, and T. Ye, Surface modification of low density polyethylene films by homogeneous catalytic ozonation. Chemical Engineering Research and Design, 2012. 90(11): p. 1800-1806.
103. Frew, J.E., P. Jones, and G. Scholes, Spectrophotometric determination of hydrogen peroxide and organic hydropheroxides at low concentrations in aqueous solution. Analytica Chimica Acta, 1983. 155(8): p. 139-150.
104. Kuznetsova, A., J. Yates, G. Zhou, J. Yang, and X. Chen, Making a superior oxide corrosion passivation layer on aluminum using ozone. Langmuir, 2001. 17(7): p. 2146-2152.
105. Yim, E.K., S.W. Pang, and K.W. Leong, Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Experimental cell research, 2007. 313(9): p. 1820-1829.
106. Anselme, K., P. Linez, M. Bigerelle, D. Le Maguer, A. Le Maguer, P. Hardouin, H. Hildebrand, A. Iost, and J. Leroy, The relative influence of the topography and chemistry of TiAl6V4 surfaces on osteoblastic cell behaviour. Biomaterials, 2000. 21(15): p. 1567-1577.
107. Selvaraj, S., S. Krishnaswamy, V. Devashya, S. Sethuraman, and U.M. Krishnan, Investigations on the membrane interactions of naringin and its complexes with copper and iron: implications for their cytotoxicity. RSC Advances, 2014. 4(87): p. 46407-46417.
108. Lim, J.Y. and M.C. Shaughnessy, Surface energy effects on osteoblast spatial growth and mineralization. Biomaterials, 2008. 29(12): p. 1776-1784.
109. Mandal, B.B., A.S. Priya, and S. Kundu, Novel silk sericin/gelatin 3-D scaffolds and 2-D films: fabrication and characterization for potential tissue engineering applications. Acta Biomaterialia, 2009. 5(8): p. 3007-3020.
110. Meng, Z., Y. Wang, C. Ma, W. Zheng, L. Li, and Y. Zheng, Electrospinning of PLGA/gelatin randomly-oriented and aligned nanofibers as potential scaffold in tissue engineering. Materials Science and Engineering: C, 2010. 30(8): p. 1204-1210.
111. Hillery, A.M., A.W. Lloyd, and J. Swarbrick, Drug delivery and targeting: for pharmacists and pharmaceutical scientists. 2002.3(5): p. 204.
112. Miranda, S.C., G.A. Silva, R.C. Hell, M.D. Martins, J.B. Alves, and A.M. Goes, Three-dimensional culture of rat BMMSCs in a porous chitosan-gelatin scaffold: A promising association for bone tissue engineering in oral reconstruction. Archives of oral biology, 2011. 56(1): p. 1-15.
113. Liuyun, J., L. Yubao, and X. Chengdong, Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering. Journal of biomedical science, 2009. 16(1): p. 65.
114. Li, X., J. Xie, X. Yuan, and Y. Xia, Coating electrospun poly (ε-caprolactone) fibers with gelatin and calcium phosphate and their use as biomimetic scaffolds for bone tissue engineering. Langmuir, 2008. 24(24): p. 14145-14150.
115. McClatchey, A.I. and A.S. Yap, Contact inhibition (of proliferation) redux. Current opinion in cell biology, 2012. 24(5): p. 685-694.
116. Holley, R.W. and J.A. Kiernan, " Contact inhibition" of cell division in 3T3 cells. Proceedings of the National Academy of Sciences, 1968. 60(1): p. 300-304.
117. Holley, R.W., Control of growth of mammalian cells in cell culture. Nature, 1975. 258(3): p. 487-490.
118. Svensson, A., E. Nicklasson, T. Harrah, B. Panilaitis, D. Kaplan, M. Brittberg, and P. Gatenholm, Bacterial cellulose as a potential scaffold for tissue engineering of cartilage. Biomaterials, 2005. 26(4): p. 419-431.
119. Aravamudhan, A., D.M. Ramos, J. Nip, M.D. Harmon, R. James, M. Deng, C.T. Laurencin, X. Yu, and S.G. Kumbar, Cellulose and collagen derived micro-nano structured scaffolds for bone tissue engineering. Journal of biomedical nanotechnology, 2013. 9(4): p. 719-731.
120. Zhang, Y., H. Ouyang, C.T. Lim, S. Ramakrishna, and Z.M. Huang, Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2005. 72(1): p. 156-165.
121. Peter, M., N. Binulal, S. Nair, N. Selvamurugan, H. Tamura, and R. Jayakumar, Novel biodegradable chitosan–gelatin/nano-bioactive glass ceramic composite scaffolds for alveolar bone tissue engineering. Chemical Engineering Journal, 2010. 158(2): p. 353-361.
122. Guo, T., J. Zhao, J. Chang, Z. Ding, H. Hong, J. Chen, and J. Zhang, Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-β1 for chondrocytes proliferation. Biomaterials, 2006. 27(7): p. 1095-1103.
123. Zhao, F., Y. Yin, W.W. Lu, J.C. Leong, W. Zhang, J. Zhang, M. Zhang, and K. Yao, Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds. Biomaterials, 2002. 23(15): p. 3227-3234.
124. Kim, H.W., H.E. Kim, and V. Salih, Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin–hydroxyapatite for tissue engineering scaffolds. Biomaterials, 2005. 26(25): p. 5221-5230.
125. Burdick, J.A. and K.S. Anseth, Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials, 2002. 23(22): p. 4315-4323.
126. Ramires, P., A. Giuffrida, and E. Milella, Three-dimensional reconstruction of confocal laser microscopy images to study the behaviour of osteoblastic cells grown on biomaterials. Biomaterials, 2002. 23(2): p. 397-406.
127. Zimmermann, K.A., J.M. LeBlanc, K.T. Sheets, R.W. Fox, and P. Gatenholm, Biomimetic design of a bacterial cellulose/hydroxyapatite nanocomposite for bone healing applications. Materials Science and Engineering: C, 2011. 31(1): p. 43-49.
128. Shi, Q., Y. Li, J. Sun, H. Zhang, L. Chen, B. Chen, H. Yang, and Z. Wang, The osteogenesis of bacterial cellulose scaffold loaded with bone morphogenetic protein-2. Biomaterials, 2012. 33(28): p. 6644-6649.
129. Fang, B., Y.Z. Wan, T.T. Tang, C. Gao, and K.R. Dai, Proliferation and osteoblastic differentiation of human bone marrow stromal cells on hydroxyapatite/bacterial cellulose nanocomposite scaffolds. Tissue Engineering Part A, 2009. 15(5): p. 1091-1098.
130. Kim, H.W., J.C. Knowles, and H.E. Kim, Hydroxyapatite and gelatin composite foams processed via novel freeze‐drying and crosslinking for use as temporary hard tissue scaffolds. Journal of Biomedical Materials Research Part A, 2005. 72(2): p. 136-145.
131. Yang, X., F. Yang, X.F. Walboomers, Z. Bian, M. Fan, and J.A. Jansen, The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. Journal of biomedical materials research Part A, 2010. 93(1): p. 247-257.
132. Chen, F.M., Y.M. Zhao, R. Zhang, T. Jin, H.H. Sun, Z.F. Wu, and Y. Jin, Periodontal regeneration using novel glycidyl methacrylated dextran (Dex-GMA)/gelatin scaffolds containing microspheres loaded with bone morphogenetic proteins. Journal of controlled release, 2007. 121(1): p. 81-90.
133. Haroun, A.A., A. Gamal-Eldeen, and D.R. Harding, Preparation, characterization and in vitro biological study of biomimetic three-dimensional gelatin–montmorillonite/cellulose scaffold for tissue engineering. Journal of Materials Science: Materials in Medicine, 2009. 20(12): p. 2527-2540.
134. Strehl, R., K. Schumacher, U. de Vries, and W.W. Minuth, Proliferating cells versus differentiated cells in tissue engineering. Tissue engineering, 2002. 8(1): p. 37-42.
135. Lanza, R., R. Langer, and J.P. Vacanti, Principles of tissue engineering. 2011.155(2):p.139.