本研究主要探討機械強度與親疏水表面對骨母細胞（7F2）和牙髓幹細胞(dental pulp stem cells, DPSCs)行為表面之影響，實驗用的基材為聚二甲基矽氧烷(polydimethyl siloxane, PDMS)，藉由調控寡聚物與硬化劑之間的重量比，製備出不同機械強度的膜材，透過氬氣低溫電漿做表面改質，將其疏水性的表面改質成親水性以利細胞的貼附。實驗將針對膜材的機械強度以及表面特性作分析，觀其對細胞貼附、細胞增生、骨分化之鹼性磷酸酶(alkaline phosphatase, ALP)表現和DPSC表面標誌分子(CD44)之螢光訊號變化之影響。
製備出的PDMS硬度為2111 kPa至160 kPa，並經氬氣電漿的改質，使其產生親水的表面特性，透過紅外線光譜分析，不同硬度的PDMS在改質前後，其化學結構無明顯的改變。
對於7F2而言，不管是疏水性或親水性的PDMS，不同的機械強度對細胞貼附無明顯的差異，另一方面，親水性的膜材有利於DPSCs的貼附，並能對機械性質作出反應，但在疏水性的材料中沒發現任何差異，研究指出膜材的機械性質對DPSCs的影響更勝過骨母細胞。
在細胞增生的研究中，7F2在高硬度且疏水表面的PDMS上，有較佳的增生情形，然而，在親水表面上卻無發現任何機械強度帶來的影響，可能親水表面利於7F2貼附，同時分泌出大量的胞外基質，而這些基質阻隔細胞對材料機械強度的辨識，因此7F2在不同硬度的膜材上，其增生表現無顯著差異。另外，DPSCs在疏水和親水的PDMS上有著不同增生情形，前者細胞在軟材料的增生優於硬材料，而後者卻是相反的情況，推測是堆積於膜材上的蛋白質產生不同的效應，此外，親水材料誘使DPSCs有良好的貼附，故使DPSCs的增生隨著機械強度的不同而有所差別。
7F2和DPSCs不管在疏水或親水的PDMS上，其ALP的分泌隨膜材硬度的減少而增加，由於，骨母細胞在高硬度的膜材上仍有良好的增生行為，因而趨緩骨分化的表現。
藉由觀察CD44的活性變化，分析親水或疏水表面且不同機械強度的膜材對DPSCs的幹細胞性質之影響。在疏水且硬材料中發現，DPSCs有較高的CD44活性，意謂此膜材能有效地保留幹細胞性質並減緩其分化行為，相反地，在任何硬度且親水的PDMS上，DPSCs的CD44卻呈現低活性的狀態，由此可知，高硬度且疏水的表面是有利於保存DPSCs的幹細胞性質。

The purpose of this research is to investigate the effect of mechanical strength and of substrates on dental pulp stem cells and osteoblasts. The influences caused by surface hydrophilicity on effects of mechanical strength were also studied. By means of manipulating the weight ratio of the hardener and oligomer in the preparation of polydimethyl siloxane (PDMS), materials’ stiffness was adjusted. The low temperature plasma of argon was applied to control the hydrophilicity. The PDMS used in this research showed the stiffness ranging from 2111 to 160 kPa. The IR spectra revealed that the chemical structures of PDMS surfaces were not greatly altered with their stiffness and hydrophilicity.
For 7F2 cells, the mechanical strength did not affect cell adhesion on both of hydrophilic and hydrophobic PDMS. On the other hand, attachment of DPSCs was not influenced by mechanical properties on hydrophobic surfaces but enhanced by stiff PDMS on hydrophilic surfaces. The results indicated that DPSCs would be more sensitive to mechanical cues of substrates, compared with mature osteoblasts.
On hydrophobic surfaces, 7F2 preferred to proliferate on the stiff PDMS. However, there was no significant difference caused by mechanical properties on the hydrophilic surfaces. This was probably due to the large amount of extracelluar matrix secreted by 7F2 retarded cells to recognize substrates’ mechanical properties.
On the other hand, DPSCs proliferation presented opposite tendencies on hydrophilic and hydrophobic PDMS. On hydrophobic surfaces, DPSCs proliferate better on softer PDMS. On hydrophilic surfaces, proliferation of DPSCs was promoted by stiff PDMS. This was probably caused the differences in protein accumulation on hydrophilic and hydrophobic surfaces. The other possibility was that the difference in DPSCs subgroups was induced by surface hydrophilicity in attachment, and these subgroups would be tended to proliferate on surfaces with different mechanical strength.
For 7F2 and DPSCs , on both hydrophilic and hydrophobic surfaces, ALP secretion increased along with the reduction of the hardness. This was because cultured osteoblasts still expressed their proliferation not osteogenic differentiation in this period.
The analysis of DPSCs on the hydrophobic and hydrophilic surfaces as well as on substrate with different mechanical strength was also performed by quantifying the expression of CD44. On hydrophobic surfaces, a longer duration of CD44 was observed on stiffer PDMS, meaning that the differentiation of DPSCs was delayed and the stem properties could be maintained for longer incubation time. Oppositely, CD44 expression was kept negative on hydrophilic surfaces with all the stiffness. The results reveal that hydrophobic and stiff surfaces would keep the stem properties of DPSCs efficiently.

1. Lanzendorf, S.E., Boyd, C.A., Wright, D.L., Muasher, S., Oehninger, S., Hodgen, G.D., Use of human gametes obtained from anonymous donors for the production of human embryonic stem cell lines. Fertil Steril., 2001. 76(1): p. 132-137.
2. Barrilleaux, B., Phinney, D. G., Prockop, D. J., O'Connor, K. C., Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng. , 2006. 12(11): p. 3007-3019.
3. Even-Ram, S., Artym, V., Yamada, K. M., Matrix control of stem cell fate. Cell, 2006. 126(4): p. 645-647.
4. Curtis, A., Riehle, M., Tissue engineering: the biophysical background. Phys. Med. Biol., 2001. 46(4): p. 47-46.
5. Griffith, L.G., Emerging design principles in biomaterials and scaffolds for tissue engineering. Ann. N.Y. Acad. Sci, 2002. 961: p. 83-95.
6. Wendy F. Liu, C.S.C., Engineering biomaterials to control cell function. Mater. Today, 2005. 8(12): p. 28-35.
7. Hutmacher, W., Scaffolds in tissue engineering bone and cartilage. Biomater. , 2000. 21(24): p. 2529-2543.
8. Agrawal, C.M., Ray, R.B., Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. J Biomed Mater Res., 2001. 55(2): p. 141-150.
9. Leong, K.F., Cheah, C. M., Chua, C. K., Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials, 2003. 24(13): p. 2363-2378.
10. Geiger, B., Spatz, J. P., Bershadsky, A. D., Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol., 2009. 10(1): p. 21-33.
11. Yim, E.K., Pang, S. W., Leong, K. W., Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp. Cell. Res., 2007. 313(9): p. 1820-9.
12. Altman, G.H., Horan, R.L., Martin, I., Farhadi, J., Stark, P.R., Volloch, V., Richmond, J.C., Vunjak-Novakovic, G., Kaplan, D.L., Cell differentiation by mechanical stress. FASEB J., 2001. 16(2): p. 270-272.
13. Metallo, C.M., Vodyanik, M. A., de Pablo, J. J., Slukvin, I. I., Palecek, S. P., The response of human embryonic stem cell-derived endothelial cells to shear stress. Biotechnol. Bioeng. , 2008. 100(4): p. 830-837.
14. Caplan, A.I., Bruder, S.P., Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends. Mol. Med., 2001. 7(6): p. 259-264.
15. Sylwia Bobis, D.J., Marcin Majka, Mesenchymal stem cells characteristics and clinical applications. 2006. 44(4): p. 215-230.
16. Chamberlain, G., Fox, J., Ashton, B., Middleton, J/, Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells., 2007. 25(11): p. 2739-2749.
17. Tuan, R.S., Kolf, C. M., Cho, E., Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther., 2007. 9(1): p. 204.
18. Baksh, D., Song, L., Tuan, R. S. , Adult mesenchymal stem cellsl: characterization, differentiation, and application in cell and gene therapy. J. Cell Mol. Med., 2004. 8(3): p. 301-316.
19. Porada Cd Fau - Zanjani, E.D., G. Zanjani Ed Fau - Almeida-Porad, and G. Almeida-Porad, Adult mesenchymal stem cells: a pluripotent population with multiple applications. Current Stem Cell Research & Therapy, 2006. 1(3): p. 365-369.
20. Gronthos S Fau - Mankani, M., et al., Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA, 2000. 97(25): p. 13625-13630.
21. Miura, M., Gronthos, S., Zhao, M., Lu, B., Fisher, L. W., Robey, P. G., Shi, S., SHED: stem cells from human exfoliated deciduous teeth. Proc. Natl. Acad. Sci. U.S.A., 2003. 100(10): p. 5807-12.
22. Seo, B.M., Miura, M., Gronthos, S., Bartold, P.M., Batouli, S., Brahim, J., Young, M., Robey, P.G., Wang, C.Y., Shi, S., Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet., 2004. 364(9429): p. 149-155.
23. Sonoyama, W., et al., Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine. PLoS ONE, 2006. 1(1): p. e79.
24. Sonoyama, W., Liu, Y., Yamaza, T., Tuan, R. S., Wang, S., Shi, S., Huang, G.T., Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. Journal of endodontics, 2008. 34(2): p. 166-171.
25. Morsczeck, C., Gotz, W., Schierholz, J., Zeilhofer, F., Kuhn, U., Mohl, C., Sippel, C., Hoffmann, K.H., Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol., 2005. 24(2): p. 155-165.
26. Dominici, M.L.B., K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A. Prockop, D., Horwitz, E.,, Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006. 8(4): p. 315-317.
27. Caplan, A.I., Mesenchymal stem cells. J Orthop Res, 1991. 9(5): p. 641-650.
28. Friedenstein, A.J., Gorskaja, J. F., Kulagina, N. N., Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol., 1976. 4(5): p. 267-274.
29. Gronthos, S., Zannettino, A.C., Hay, S.J., Shi, S., Graves, S.E., Kortesidis, A., Simmons, P.J., Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J. Cell. Sci., 2003. 116(9): p. 1827-1835.
30. Prockop, D.J., Marrow stromal cells as stem cells for nonhematopoietic tissues. Science, 1997. 276(5309): p. 71-74.
31. Dominici, M., et al., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006. 8(4): p. 315-7.
32. Schieker, M., Pautke, C., Haasters, F., Schieker, J., Docheva, D., Bocker, W., Guelkan, H., Neth, P., Jochum, M., Mutschler, W.,, Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour immunofluorescence. J Anat, 2007. 210(5): p. 592-599.
33. Docheva, D., Popov, C., Mutschler, W., Schieker, M., Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J. Cell. Mol. Med., 2007. 11(1): p. 21-38.
34. Pierdomenico, L., Bonsi, L., Calvitti, M., Rondelli, D., Arpinati, M., Chirumbolo, G., Becchetti, E., Marchionni, C., Alviano, F., Fossati, V., Staffolani, N., Franchina, M., Grossi, A., Bagnara, G. P., Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation, 2005. 80(6): p. 836-842.
35. Karaoz, E., Dogan, B. N., Aksoy, A., Gacar, G., Akyuz, S., Ayhan, S., Genc, Z. S., Yuruker, S., Duruksu, G., Demircan, P. C., Sariboyaci, A. E., , Isolation and in vitro characterisation of dental pulp stem cells from natal teeth. Histochem. Cell. Biol., 2010. 133(1): p. 95-112.
36. Huang, G.T., Pulp and dentin tissue engineering and regeneration: current progress. Regen Med, 2009. 4(5): p. 697-707.
37. Lindroos, B., Maenpaa, K., Ylikomi, T., Oja, H., Suuronen, R., Miettinen, S., Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem. Biophys. Res. Commun. , 2008. 368(2): p. 329-335.
38. Nam, H., Lee, G., Identification of novel epithelial stem cell-like cells in human deciduous dental pulp. Biochem. Biophys. Res. Commun., 2009. 386(1): p. 135-9.
39. Rodriguez-Lozano, F.J., Bueno, C., Insausti, C. L. , Meseguer, L., Ramirez, M. C., Blanquer, M., Marin, N., Martinez, S., Moraleda, J. M., Mesenchymal stem cells derived from dental tissues. Int. Endod. J., 2011. 44(9): p. 800-806.
40. Shi, S., Bartold, P. M., Miura, M., Seo, B. M., Robey, P. G., Gronthos, S., The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res, 2005. 8(3): p. 191-199.
41. Kawashima, N., Characterisation of dental pulp stem cells: a new horizon for tissue regeneration? Arch. Oral. Biol., 2012. 57(11): p. 1439-58.
42. Gronthos, S., Brahim, J., Li, W., Fisher, L. W., Cherman, N., Boyde, A., DenBesten, P., Robey, P. G., Shi, S.,, Stem cell properties of human dental pulp stem cells. J. Dent. Res., 2002. 81(8): p. 531-535.
43. d'Aquino, R., Graziano, A., Sampaolesi, M., Laino, G., Pirozzi, G., De Rosa, A., Papaccio, G., Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ., 2007. 14(6): p. 1162-1171.
44. Laino, G., d'Aquino, R., Graziano, A., Lanza, V., Carinci, F., Naro, F., Pirozzi, G., Papaccio, G., A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). J. Bone Miner. Res., 2005. 20(8): p. 1394-1402.
45. Zhang W Fau - Walboomers, X.F., et al., Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Engineering, 2006. 12(10): p. 2813-2823.
46. Huang, G.T., Gronthos, S., Shi, S., Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res, 2009. 88(9): p. 792-806.
47. Nakamura, S., Yamada, Y., Katagiri, W., Sugito, T., Ito, K., Ueda, M., Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. J. Endod., 2009. 35(11): p. 1536-1542.
48. Yu, J., Wang, Y., Deng, Z., Tang, L., Li, Y., Shi, J., Jin, Y.,, Odontogenic capability: bone marrow stromal stem cells versus dental pulp stem cells. Biol. Cell., 2007. 99(8): p. 465-74.
49. Papaccio, G., et al., Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair. J Cell Physiol, 2006. 208(2): p. 319-25.
50. Yu J Fau - Deng, Z., et al., Differentiation of dental pulp stem cells into regular-shaped dentin-pulp complex induced by tooth germ cell conditioned medium. Tissue engineering, 2006. 12(11): p. 3097-3105.
51. Ding, G., Wang, W., Liu, Y., An, Y., Zhang, C., Shi, S., Wang, S., Effect of cryopreservation on biological and immunological properties of stem cells from apical papilla. J. Cell. Physiol., 2010. 223(2): p. 415-422.
52. Graziano, A., d'Aquino, R., Laino, G., Papaccio, G., Dental pulp stem cells: a promising tool for bone regeneration. Stem. Cell. Rev., 2008. 4(1): p. 21-6.
53. Ding G Fau - Liu, Y., et al., Suppression of T cell proliferation by root apical papilla stem cells in vitro. Cells Tissues Organs, 2010. 191(5): p. 357-364.
54. Huang, A.H., Snyder, B. R., Cheng, P. H., Chan, A. W., Putative dental pulp-derived stem/stromal cells promote proliferation and differentiation of endogenous neural cells in the hippocampus of mice. Stem Cells, 2008. 26(10): p. 2654-2663.
55. Ikeda, E., Yagi, K., Kojima, M., Yagyuu, T., Ohshima, A., Sobajima, S., Tadokoro, M., Katsube, Y., Isoda, K., Kondoh, M., Kawase, M., Go, M. J., Adachi, H., Yokota, Y., Kirita, T., Ohgushi, H., Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease. Differentiation, 2008. 76(5): p. 495-505.
56. Huang, G.T., Yamaza, T., Shea, L. D., Djouad, F., Kuhn, N. Z., Tuan, R. S., Shi, S., Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng. Part A., 2010. 16(2): p. 605-615.
57. Prescott, R.S., Alsanea, R., Fayad, M. I., Johnson, B. R., Wenckus, C. S., Hao, J., John, A. S., George, A., In vivo generation of dental pulp-like tissue by using dental pulp stem cells, a collagen scaffold, and dentin matrix protein 1 after subcutaneous transplantation in mice. Journal of endodontics, 2008. 34(4): p. 421-426.
58. Eslaminejad, M.B., Bordbar, S., Nazarian, H., Odontogenic differentiation of dental pulp-derived stem cells on tricalcium phosphate scaffolds. Journal of Dental Sciences, 2013.
59. Demarco, F.F., Casagrande, L., Zhang, Z., Dong, Z., Tarquinio, S. B., Zeitlin, B. D., Shi, S., Smith, A. J., Nor, J. E., Effects of morphogen and scaffold porogen on the differentiation of dental pulp stem cells. J. Endod., 2010. 36(11): p. 1805-1811.
60. Wang, J., Liu, X., Jin, X., Ma, H., Hu, J., Ni, L., Ma, PX., The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(L-lactic acid) scaffolds in vitro and in vivo. Acta Biomater., 2010. 6(10): p. 3856-3863.
61. Wang, J., Ma, H., Jin, X., Hu, J., Liu, X., Ni, L., Ma, P. X., The effect of scaffold architecture on odontogenic differentiation of human dental pulp stem cells. Biomaterials, 2011. 32(31): p. 7822-30.
62. Sollazzo, V., Lucchese, A., Palmieri, A., Carnevali, G., Iaccarino, C., Zollino, I., Della Valle, M., Pezzetti, F., Brunelli, G., Carinci, F., Calcium sulfate stimulates pulp stem cells towards osteoblasts differentiation. Int. J. Immunopharmacol 2011. 24: p. 51S-57S.
63. Galli, D., Benedetti, L., Bongio, M., Maliardi, V., Silvani, G., Ceccarelli, G., Ronzoni, F., Conte, S., Benazzo, F., Graziano, A., Papaccio, G., Sampaolesi, M., Cusella De Angelis, M. G., In vitro osteoblastic differentiation of human mesenchymal stem cells and human dental pulp stem cells on poly- L -lysine-treated titanium-6-aluminium-4- vanadium. J. Biomed. Mater. Res. Part A, 2011. 97 A(2): p. 118-126.
64. Bae, W.J., Min, K. S., Kim, J. J., Kim, J. J., Kim, H. W., Kim, E. C., Odontogenic responses of human dental pulp cells to collagen/nanobioactive glass nanocomposites. Dent. Mater., 2012. 28(12): p. 1271-9.
65. Mangano, C., De Rosa, A., Desiderio, V., d'Aquino, R., Piattelli, A., De Francesco, F., Tirino, V., Mangano, F., Papaccio, G.. The osteoblastic differentiation of dental pulp stem cells and bone formation on different titanium surface textures. Biomaterials., 2010. 31(13): p. 3543-3551.
66. Daley, W.P., Peters, S. B., Larsen, M., Extracellular matrix dynamics in development and regenerative medicine. J. Cell. Sci., 2008. 121(3): p. 255-264.
67. Vinay, K., Abul K. Abbas, Nelson, F., Robbins & Cotran Pathologic Basis of Disease. 7 ed. 2005.
68. Giancotti, F.G., A structural view of integrin activation and signaling. Dev. Cell., 2003. 4(2): p. 149-151.
69. Taipale, J., Keski-Oja, J., Growth factors in the extracellular matrix. FASEB J., 1997. 11(1): p. 51-59.
70. Pompe T., S.K., Alberti K., Zandstra P., Werner C., Immobilization of growth factors on solid supports for the modulation of stem cell fate. Nat Protoc., 2010. 5: p. 1042-1050.
71. Bakeine, G.J., Ban, J., Grenci, G., Pozzato, A., Zilio, S. D., Prasciolu, M., Businaro, L., Tormen, M., Ruaro, M. E., Design, fabrication and evaluation of nanoscale surface topography as a tool in directing differentiation and organisation of embryonic stem-cell-derived neural precursors. Microelectron. Eng. , 2009. 86(4-6): p. 1435-1438.
72. Engler, A.J., Sen, S., Sweeney, H. L., Discher, D. E., Matrix elasticity directs stem cell lineage specification. Cell, 2006. 126(4): p. 677-89.
73. Kshitiz, M.E., Hubbi, E. H., Ahn, J., Downey, J., Afzal, D. H., Kim, S., Rey, C., Chang, A., Kundu, G. L., Semenza, R. M., Abraham, A., Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. Sci. Signal., 2012. 5(227): p. ra41.
74. dela Paz, N.G., Walshe, T. E., Leach, L. L., Saint-Geniez, M., D'Amore, P. A., Role of shear-stress-induced VEGF expression in endothelial cell survival. J. Cell. Sci., 2012. 125: p. 831-43.
75. Kshitiz, P., J. S., Kim, P., Helen, W., Engler, A. J., Levchenko, A., Kim, D. H., Control of stem cell fate and function by engineering physical microenvironments. Integr. Biol., 2012. 4: p. 1008-1018.
76. Dennis E., D., Paul, J., Yu-li, W., Tissue cells feel and respond to the stiffness of their substrate. Science, 2005. 310: p. 1139-1143.
77. Smith, K.E., Hyzy, S. L., Sunwoo, M., Gall, K. A., Schwartz, Z., Boyan, B. D., The dependence of MG63 osteoblast responses to (meth)acrylate-based networks on chemical structure and stiffness. Biomaterials, 2010. 31(24): p. 6131-41.
78. Keogh, M.B., O'Brien, F. J., Daly, J. S., Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen-GAG scaffold. Acta Biomater, 2010. 6(11): p. 4305-13.
79. Cox, T.R., Erler, J.T., Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis. Model. Mech., 2011. 4(2): p. 165-78.
80. Trappmann, B., Gautrot, J. E., Connelly, J. T., Strange, D. G., Li, Y., Oyen, M. L., Cohen Stuart, M. A., Boehm, H., Li, B., Vogel, V., Spatz, J. P., Watt, F. M., Huck, W. T., Extracellular-matrix tethering regulates stem-cell fate. Nature Materials, 2012. 11: p. 642-649.
81. Van Tam, J.K., Uto, K., Ebara, M., Pagliari, S., Forte, G., Aoyagi, T., Mesenchymal stem cell adhesion but not plasticity is affected by high substrate stiffness. Sci. Technol. Adv. Mater., 2012. 13(6): p. 064205.
82. Mason, B.N., Califano, J. P., Reinhart-King, C. A., Matrix stiffness: A regulator of cellular behavior and tissue formation. Engineering Biomaterials for Regenerative Medicine, 2012: p. 19-37.
83. Lo, C.M., Wang, H. B., Dembo, M., Wang, Y. L., Cell movement is guided by the rigidity of the substrate. Biophys J., 2000. 79(1): p. 144-152.
84. Joong-Yull Park, S.-J.Y., Eun-Joong Lee, Dae-Ho Lee, Ji-Young Kim, Sang-Hoon Lee, Increased poly(dimethylsiloxane) stiffness improves viability and morphology of mouse fibroblast cells. J. BIOCHIP 2010. 4(3): p. 230-236.
85. Wang, L., Sun, B., Ziemer, K. S., Barabino, G. A., Carrier, R. L., Chemical and physical modifications to poly(dimethylsiloxane) surfaces affect adhesion of Caco-2 cells. J. Biomed. Mater. Res. A, 2010. 93(4): p. 1260-71.
86. Wang, P.Y., Tsai, W. B., Voelcker, N. H., Screening of rat mesenchymal stem cell behaviour on polydimethylsiloxane stiffness gradients. Acta Biomater., 2012. 8(2): p. 519-30.
87. Rowlands, A.S., George, P.A., Cooper-White, J.J., Directing osteogenic and myogenic differentiation of MSCs: interplay of stiffness and adhesive ligand presentation. Am. J. Physiol., Cell Physiol., 2008. 295(4): p. 1037-1044.
88. McArthur, S.L., Colley, H. E., Mishra, G., Scutt, A. M. , Plasma polymer coatings to support mesenchymal stem cell adhesion, growth and differentiation on variable stiffness silicone elastomers. Plasma Processes and Polymers, 2009. 6(12): p. 831–839.
89. Leipzig, N.D., Shoichet, M. S., The effect of substrate stiffness on adult neural stem cell behavior. Biomaterials, 2009. 30(36): p. 6867-78.
90. Evans, N.D., Minelli, C., Gentleman, E., LaPointe, V., Patankar, S. N., Kallivretaki, M., Chen, X., Roberts, C. J., Stevens, M. M., Substrate stiffness affects early differntiation events in embryonic stem cells. Eur. Cell. Mater., 2009. 18: p. 1-14.
91. Witkowska-Zimny, M., Walenko, K., Wałkiewicz, A. E., Pojda, Z., Przybylski, J., Lewandowska-Szumieł, M., Effect of substrate stiffness on differentiation of umbilical cord stem cells. Acta biochimica. Polonica., 2012. 59(2): p. 261-264.
92. Viale-Bouroncle, S., Gosau, M., Kupper, K., Mohl, C., Brockhoff, G., Reichert, T. E., Schmalz, G., Ettl, T., Morsczeck, C., Rigid matrix supports osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Differentiation, 2012. 84(5): p. 366-70.
93. Viale-Bouroncle, S., Vollner, F., Mohl, C., Kupper, K., Brockhoff, G., Reichert, T. E., Schmalz, G., Morsczeck, C., Soft matrix supports osteogenic differentiation of human dental follicle cells. Biochem. Biophys. Res. Commun., 2011. 410(3): p. 587-92.
94. Wang, Y., Wang, G., Luo, X., Qiu, J., Tang, C., Substrate stiffness regulates the proliferation, migration, and differentiation of epidermal cells. Burns, 2012. 38(3): p. 414-420.
95. Palchesko, R.N., Zhang, L., Sun, Y., Feinberg, A. W., Development of polydimethylsiloxane substrates with tunable elastic modulus to study cell mechanobiology in muscle and nerve. PLoS. One, 2012. 7(12): p. 1-13.
96. Fioretta, E.S., Fledderus, J. O., Baaijens, F. P., Bouten, C. V., Influence of substrate stiffness on circulating progenitor cell fate. J. Biomech., 2012. 45(5): p. 736-44.
97. Witkowska-Zimny, M., Walenko, K., Wrobel, E., Mrowka, P., Mikulska, A., Przybylski, J., Effect of substrate stiffness on the osteogenic differentiation of bone marrow stem cells and bone-derived cells. Cell. Biol. Int., 2013. 37(6): p. 608-16.
98. Keddie, J.L., Z. Tabatabaian, Z., Jeyens, C., Parbhoo, B., , Influence of interfaces on the rates of crosslinking in poly(dimethyl siloxane) coatings J. Polym. Sci., Part A: Polym. Chem., 2004. 42: p. 1421-1431.
99. Fuard, D., Tzvetkova-Chevolleau, T., Decossas, S., Tracqui, P., Schiavone, P., Optimization of poly-di-methyl-siloxane (PDMS) substrates for studying cellular adhesion and motility. Microelectron. Eng. , 2008. 85(5-6): p. 1289-1293.
100. Whitesides, G.M., Duffy, David C., Cooper McDonald, J., Schueller, Olivier J. A. , Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal. Chem.,, 1998. 70 (23): p. 4974-4987.
101. Min-Hsien, W., Simple poly(dimethylsiloxane) surface modification to control cell adhesion. Surf. Interface Anal. , 2009. 41(1): p. 11-16.
102. Whitesides, G.M., Kenis, Paul J. A., Ismagilov, Rustem F. , Microfabrication inside capillaries using multiphase laminar flow patterning. Science, 1999. 285(5424): p. 83-85.
103. Ionescu-Zanetti, C., Shaw, R. M., Seo, J., Jan, Y. N., Jan, L. Y., Lee, L. P., Mammalian electrophysiology on a microfluidic platform. Proc. Natl. Acad. Sci. U.S.A., 2005. 102(26): p. 9112-7.
104. Chippendale, T.W.E., El Haj, A. J., Coopman, K., Rafiq, Q., Hewitt, C. J., Isolation of Mesenchymal Stem Cells from Bone Marrow Aspirate. Comprehensive Biotechnology, 2011. 5: p. 115-123.
105. Huang, Y., Xue, Z., Gao, H., Nix, W. D., Xia, Z. C., A study of microindentation hardness tests by mechanism-based strain gradient plasticity. J. Mater. Res., 1999. 15(8): p. 1786-1796.
106. Hutchinson, J.W., Neale, K. W., Influence of strain-rate sensitivity on necking under uniaxial tension. Acta Metallurgica, 1977. 25(8): p. 839-846.
107. Ming-Hwa, H., Jia-Bin, Hung, The phenotypes of osteoblastic cells on surfaces with different mechanical properties, in Chemical Engineering2009, National Taiwan University of Science and Technology.
108. Mehta, G., Kiel, M. J., Lee, J. W., Kotov, N., Linderman, J. J., Takayama, S., Polyelectrolyte-clay-protein layer films on microfluidic PDMS bioreactor surfaces for primary murine bone marrow culture. Adv. Funct. Mater. , 2007. 17(15): p. 2701-2709.
109. De Silva, M.N., Desai, R., Odde, D.J., Micro-patterning of animal cells on PDMS substrates in the presence of serum without use of adhesion inhibitors. Biomed Microdevices., 2004. 6(3): p. 219-222.
110. Lateef, S.S., Boateng, S., Hartman, T.J., Crot, C.A., Russell, B., Hanley, L.. GRGDSP peptide-bound silicone membranes withstand mechanical flexing in vitro and display enhanced fibroblast adhesion. Biomaterials, 2002. 23(15): p. 3159-3168.
111. Yang, Y., Kulangara, K., Lam, R. T., Dharmawan, R., Leong, K. W., Effects of topographical and mechanical property alterations induced by oxygen plasma modification on stem cell behavior. ACS Nano., 2012. 6(10 ): p. 8591-8598.
112. Swary, F., Ming-Hua, H., Osteoblastic cells behaviors on micro-patterned surfaces, in Chemical Engineering2007, National Taiwan University of Science and Technology.
113. S. Kitova, M.M., G. Danev, Soft plasma treatment of polymer surfaces. Journal of Optoelectronics and Advanced Materials 2005. 7(1): p. 249-252.
114. Albertsson, A.C., Olander, B., Wirsen, A. , Silicone elastomers with controlled surface composition using argon or hydrogen plasma treatment. J. Appl. Polym. Sci. , 2003. 90(5): p. 1378-1383.
115. Hong, S.M., et al., Hydrophilic Surface Modification of PDMS Using Atmospheric RF Plasma. Journal of Physics: Conference Series, 2006. 34: p. 656-661.
116. Bodas, D., Khan-Malek, C., Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment—An SEM investigation. Sens. Actuators, B 2007. 123(1): p. 368-373.
117. Eddington, D.T., Puccinelli, J. P., Beebe, D. J., Thermal aging and reduced hydrophobic recovery of polydimethylsiloxane. Sens. Actuators, B 2006. 114(1): p. 170-172.
118. Gharibi, B., Hughes, F. J., Effects of medium supplements on proliferation,differentiation potential, and in vitro expansion of mesenchymal stem cells. Stem Cells Transl. Med., 2012. 1(11): p. 771-782.
119. Lee, Y.J., Park, S.J., Lee, W.K., Ko, J.S., Kim, H.M., MG63 osteoblastic cell adhesion to the hydrophobic surface precoated with recombinant osteopontin fragments. Biomaterials, 2003. 24(6): p. 1059-1066.
120. Zhang, Y., Andrukhov, O., Berner, S., Matejka, M., Wieland, M., Rausch-Fan, X., Schedle, A., Osteogenic properties of hydrophilic and hydrophobic titanium surfaces evaluated with osteoblast-like cells (MG63) in coculture with human umbilical vein endothelial cells (HUVEC). Dent. Mater., 2010. 26(11): p. 1043-51.
121. Tsai, S.W., Liou, H. M., Lin, C. J., Kuo, K. L., Hung, Y. S., Weng, R. C., Hsu, F. Y., MG63 osteoblast-like cells exhibit different behavior when grown on electrospun collagen matrix versus electrospun gelatin matrix. PLoS One, 2012. 7(2): p. 1-11.
122. Khatiwala, C.B., S.R. Peyton, and A.J. Putnam, Intrinsic mechanical properties of the extracellular matrix affect the behavior of pre-osteoblastic MC3T3-E1 cells. American Journal of Physiology - Cell Physiology, 2006. 290(6): p. 1640-1650.
123. Altankov, G., Groth, Th., Reorganization of substratum-bound fibronectin on hydrophilic and hydrophobic materials is related to biocompatibility. J. Mater. Sci. - Mater. Med., 1994. 5(9-10): p. 732-737.
124. Winer, J.P., Janmey, P. A., McCormick, M. E., Funaki, M., Bone marrow-derived human mesenchymal stem cells become quiescent on soft substrates but remain responsive to chemical or mechanical stimuli. Tissue Eng. Part A. , 2009. 15(1): p. 147-154.
125. Huang, J., Yue, Y., Zheng, C., Vroman effect of plasma protein adsorption to biomaterials surfaces. 1999. 16(3): p. 371-376.
126. Noh, H., Vogler, E. A., Volumetric interpretation of protein adsorption: competition from mixtures and the Vroman effect. Biomaterials, 2007. 28(3): p. 405-22.
127. Lee, J.N., Jiang, X., Ryan, D., Whitesides, G. M., Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane). Langmuir., 2004. 20(26): p. 11684-11691.
128. Gribova, V., Auzely-Velty, R., Picart, C., Polyelectrolyte multilayer assemblies on materials surfaces: From cell adhesion to tissue engineering. Chem. Mater., 2012. 24(5): p. 854-869.
129. Stein, G.S., Lian, J. B., Stein, J. L., Van Wijnen, A. J., Montecino, M., Transcriptional control of osteoblast growth and differentiation. Physiol Rev., 1996. 76(2): p. 593-629.
130. Keogh, M.B., F.J. O'Brien, and J.S. Daly, Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen-GAG scaffold. Acta Biomater, 2010. 6(11): p. 4305-13.