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Volumn 19, Issue 7, 2013, Pages 538-549

Biomimetic three-dimensional anisotropic geometries by uniaxial stretch of poly(ε-Caprolactone) films for mesenchymal stem cell proliferation, alignment, and myogenic differentiation

Author keywords

[No Author keywords available]

Indexed keywords

ALIGNMENT; ANISOTROPY; BIOMIMETICS; CELL CULTURE; CELL PROLIFERATION; GENE EXPRESSION; STEM CELLS; SURFACE TOPOGRAPHY; THREE DIMENSIONAL; TISSUE; TISSUE ENGINEERING;

EID: 84878300170     PISSN: 19373384     EISSN: 19373392     Source Type: Journal    
DOI: 10.1089/ten.tec.2012.0472     Document Type: Article
Times cited : (52)

References (51)
  • 1
    • 70849130059 scopus 로고    scopus 로고
    • Designing materials to direct stem-cell fate
    • Lutolf, M.P., Gilbert, P.M., and Blau, H.M. Designing materials to direct stem-cell fate. Nature 462, 433, 2009.
    • (2009) Nature , vol.462 , pp. 433
    • Lutolf, M.P.1    Gilbert, P.M.2    Blau, H.M.3
  • 2
    • 77953723114 scopus 로고    scopus 로고
    • Polymer nanofibrous structures: Fabrication, biofunctionalization, and cell interactions
    • Beachley, V., and Wen, X. Polymer nanofibrous structures: fabrication, biofunctionalization, and cell interactions. Prog Polym Sci 35, 868, 2010.
    • (2010) Prog Polym Sci , vol.35 , pp. 868
    • Beachley, V.1    Wen, X.2
  • 3
    • 77955845322 scopus 로고    scopus 로고
    • The interaction between nanoscale surface features and mechanical loading and its effect on osteoblast-like cells behavior
    • Prodanov, L., te Riet, J., Lamers, E., Domanski, M., Luttge, R., van Loon, J.J., Jansen, J.A., and Walboomers, X.F. The interaction between nanoscale surface features and mechanical loading and its effect on osteoblast-like cells behavior. Biomaterials 31, 7758, 2010.
    • (2010) Biomaterials , vol.31 , pp. 7758
    • Prodanov, L.1    Te Riet, J.2    Lamers, E.3    Domanski, M.4    Luttge, R.5    Van Loon, J.J.6    Jansen, J.A.7    Walboomers, X.F.8
  • 4
  • 5
    • 0031406715 scopus 로고    scopus 로고
    • Correlation of vascular smooth muscle cell morphology observed by scanning electron microscopy with transmission electron microscopy
    • Krizmanich, W.J., and Lee, R.M. Correlation of vascular smooth muscle cell morphology observed by scanning electron microscopy with transmission electron microscopy. Exp Mol Pathol 64, 157, 1997.
    • (1997) Exp Mol Pathol , vol.64 , pp. 157
    • Krizmanich, W.J.1    Lee, R.M.2
  • 7
    • 60549116293 scopus 로고    scopus 로고
    • Development of cell-selective films for layered coculturing of vascular progenitor cells
    • Chong, M.S.K., Chan, J., Choolani, M., Lee, C.-N., and Teoh, S.-H. Development of cell-selective films for layered coculturing of vascular progenitor cells. Biomaterials 30, 2241, 2009.
    • (2009) Biomaterials , vol.30 , pp. 2241
    • Chong, M.S.K.1    Chan, J.2    Choolani, M.3    Lee, C.-N.4    Teoh, S.-H.5
  • 8
    • 79959845985 scopus 로고    scopus 로고
    • Stem cell differentiation to epidermal lineages on electrospun nanofibrous substrates for skin tissue engineering
    • Jin, G., Prabhakaran, M.P., and Ramakrishna, S. Stem cell differentiation to epidermal lineages on electrospun nanofibrous substrates for skin tissue engineering. Acta Biomater 7, 3113, 2011.
    • (2011) Acta Biomater , vol.7 , pp. 3113
    • Jin, G.1    Prabhakaran, M.P.2    Ramakrishna, S.3
  • 9
    • 77950427004 scopus 로고    scopus 로고
    • Geometric cues for directing the differentiation of mesenchymal stem cells
    • Kilian, K.A., Bugarija, B., Lahn, B.T., and Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. PNAS 107, 4872, 2010.
    • (2010) PNAS , vol.107 , pp. 4872
    • Kilian, K.A.1    Bugarija, B.2    Lahn, B.T.3    Mrksich, M.4
  • 11
    • 66949178254 scopus 로고    scopus 로고
    • Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties
    • Xie, J., MacEwan, M.R., Li, X., Sakiyama-Elbert, S.E., and Xia, Y. Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties. ACS Nano 3, 1151, 2009.
    • (2009) ACS Nano , vol.3 , pp. 1151
    • Xie, J.1    Macewan, M.R.2    Li, X.3    Sakiyama-Elbert, S.E.4    Xia, Y.5
  • 12
    • 0031421084 scopus 로고    scopus 로고
    • Topographical control of cells
    • Curtis, A., and Wilkinson, C. Topographical control of cells. Biomaterials 18, 1573, 1997.
    • (1997) Biomaterials , vol.18 , pp. 1573
    • Curtis, A.1    Wilkinson, C.2
  • 13
    • 65249151850 scopus 로고    scopus 로고
    • Nanopatterning of collagen scaffolds improve the mechanical properties of tissue engineered vascular grafts
    • Zorlutuna, P., Elsheikh, A., and Hasirci, V. Nanopatterning of collagen scaffolds improve the mechanical properties of tissue engineered vascular grafts. Biomacromolecules 10, 814, 2009.
    • (2009) Biomacromolecules , vol.10 , pp. 814
    • Zorlutuna, P.1    Elsheikh, A.2    Hasirci, V.3
  • 14
    • 4344661143 scopus 로고    scopus 로고
    • Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells
    • Karuri, N.W., Liliensiek, S., Teixeira, A.I., Abrams, G., Campbell, S., Nealey, P.F., and Murphy, C.J. Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells. J Cell Sci 117, 3153, 2004.
    • (2004) J Cell Sci , vol.117 , pp. 3153
    • Karuri, N.W.1    Liliensiek, S.2    Teixeira, A.I.3    Abrams, G.4    Campbell, S.5    Nealey, P.F.6    Murphy, C.J.7
  • 15
    • 77953650474 scopus 로고    scopus 로고
    • Regulating orientation and phenotype of primary vascular smooth muscle cells by biodegradable films patterned with arrays of microchannels and discontinuous microwalls
    • Cao, Y., Poon, Y.F., Feng, J., Rayatpisheh, S., Chan, V., and Chan-Park, M.B. Regulating orientation and phenotype of primary vascular smooth muscle cells by biodegradable films patterned with arrays of microchannels and discontinuous microwalls. Biomaterials 31, 6228, 2010.
    • (2010) Biomaterials , vol.31 , pp. 6228
    • Cao, Y.1    Poon, Y.F.2    Feng, J.3    Rayatpisheh, S.4    Chan, V.5    Chan-Park, M.B.6
  • 16
    • 77949652632 scopus 로고    scopus 로고
    • Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/ groove pattern arrays
    • Lee, M.R., Kwon, K.W., Jung, H., Kim, H.N., Suh, K.Y., Kim, K., and Kim, K.-S. Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/ groove pattern arrays. Biomaterials 31, 4360, 2010.
    • (2010) Biomaterials , vol.31 , pp. 4360
    • Lee, M.R.1    Kwon, K.W.2    Jung, H.3    Kim, H.N.4    Suh, K.Y.5    Kim, K.6    Kim, K.-S.7
  • 17
    • 84855471991 scopus 로고    scopus 로고
    • Direct laser machining-induced topographic pattern promotes up-regulation of myogenic markers in human mesenchymal stem cells
    • Li, H.Q., Wen, F., Wong, Y.S., Boey, F.Y.C., Subbu, V.S., Leong, D.T., Ng, K.W., Ng, G.K.L., and Tan, L.P. Direct laser machining-induced topographic pattern promotes up-regulation of myogenic markers in human mesenchymal stem cells. Acta Biomater 8, 531, 2012.
    • (2012) Acta Biomater , vol.8 , pp. 531
    • Li, H.Q.1    Wen, F.2    Wong, Y.S.3    Boey, F.Y.C.4    Subbu, V.S.5    Leong, D.T.6    Ng, K.W.7    Ng, G.K.L.8    Tan, L.P.9
  • 18
    • 58649088036 scopus 로고    scopus 로고
    • A novel approach to align adult neural stem cells on micropatterned conduits for peripheral nerve regeneration: A feasibility study
    • Hsu, S.H., Su, C.H., and Chiu, I.M. A novel approach to align adult neural stem cells on micropatterned conduits for peripheral nerve regeneration: a feasibility study. Artif Organs 33, 26, 2009.
    • (2009) Artif Organs , vol.33 , pp. 26
    • Hsu, S.H.1    Su, C.H.2    Chiu, I.M.3
  • 19
    • 0038107091 scopus 로고    scopus 로고
    • Epithelial contact guidance on well-defined micro- and nanostructured substrates
    • Teixeira, A.I., Abrams, G.A., Bertics, P.J., Murphy, C.J., and Nealey, P.F. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J Cell Sci 116, 1881, 2003.
    • (2003) J Cell Sci , vol.116 , pp. 1881
    • Teixeira, A.I.1    Abrams, G.A.2    Bertics, P.J.3    Murphy, C.J.4    Nealey, P.F.5
  • 20
    • 77949654584 scopus 로고    scopus 로고
    • The effect of micronscale anisotropic cross patterns on fibroblast migration
    • Jeon, H., Hidai, H., Hwang, D.J., Healy, K.E., and Grigoropoulos, C.P. The effect of micronscale anisotropic cross patterns on fibroblast migration. Biomaterials 31, 4286, 2010.
    • (2010) Biomaterials , vol.31 , pp. 4286
    • Jeon, H.1    Hidai, H.2    Hwang, D.J.3    Healy, K.E.4    Grigoropoulos, C.P.5
  • 21
    • 55249093369 scopus 로고    scopus 로고
    • The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages
    • Xie, J., Willerth, S., Li, X., Macewan, M., Rader, A., Sakiyamaelbert, S., and Xia, Y. The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials 30, 354, 2009.
    • (2009) Biomaterials , vol.30 , pp. 354
    • Xie, J.1    Willerth, S.2    Li, X.3    Macewan, M.4    Rader, A.5    Sakiyamaelbert, S.6    Xia, Y.7
  • 22
    • 77957588918 scopus 로고    scopus 로고
    • The return of a forgotten polymer-polycaprolactone in the 21st century
    • Woodruff, M.A., and Hutmacher, D.W. The return of a forgotten polymer-polycaprolactone in the 21st century. Prog Polym Sci 35, 1217, 2010.
    • (2010) Prog Polym Sci , vol.35 , pp. 1217
    • Woodruff, M.A.1    Hutmacher, D.W.2
  • 23
    • 77049105599 scopus 로고    scopus 로고
    • Surface functionalization of polycaprolactone films via surface-initiated atom transfer radical polymerization for covalently coupling celladhesive biomolecules
    • Xu, F.J., Wang, Z.H., and Yang, W.T. Surface functionalization of polycaprolactone films via surface-initiated atom transfer radical polymerization for covalently coupling celladhesive biomolecules. Biomaterials 31, 3139, 2010.
    • (2010) Biomaterials , vol.31 , pp. 3139
    • Xu, F.J.1    Wang, Z.H.2    Yang, W.T.3
  • 24
    • 54449092196 scopus 로고    scopus 로고
    • Bioengineered threelayered robust and elastic artery using hemodynamicallyequivalent pulsatile bioreactor
    • Iwasaki, K., Kojima, K., Kodama, S., Paz, A.C., Chambers, M., Umezu, M., and Vacanti, C.A. Bioengineered threelayered robust and elastic artery using hemodynamicallyequivalent pulsatile bioreactor. Circulation 118, S52, 2008.
    • (2008) Circulation , vol.118
    • Iwasaki, K.1    Kojima, K.2    Kodama, S.3    Paz, A.C.4    Chambers, M.5    Umezu, M.6    Vacanti, C.A.7
  • 25
    • 34548107032 scopus 로고    scopus 로고
    • Current state of the art in myocardial tissue engineering
    • Giraud, M.N., Armbruster, C., Carrel, T., and Tevaearai, H.T. Current state of the art in myocardial tissue engineering. Tissue Eng 13, 1825, 2007.
    • (2007) Tissue Eng , vol.13 , pp. 1825
    • Giraud, M.N.1    Armbruster, C.2    Carrel, T.3    Tevaearai, H.T.4
  • 26
    • 36549084632 scopus 로고    scopus 로고
    • The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation
    • Chew, S.Y., Mi, R., Hoke, A., and Leong, K.W. The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation. Biomaterials 29, 653, 2008.
    • (2008) Biomaterials , vol.29 , pp. 653
    • Chew, S.Y.1    Mi, R.2    Hoke, A.3    Leong, K.W.4
  • 27
    • 33744912473 scopus 로고    scopus 로고
    • Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications
    • Sarkar, S., Lee, G.Y., Wong, J.Y., and Desai, T.A. Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications. Biomaterials 27, 4775, 2006.
    • (2006) Biomaterials , vol.27 , pp. 4775
    • Sarkar, S.1    Lee, G.Y.2    Wong, J.Y.3    Desai, T.A.4
  • 29
    • 4444348926 scopus 로고    scopus 로고
    • Micro and nano-fabrication of biodegradable polymers for drug delivery
    • Lu, Y., and Chen, S.C. Micro and nano-fabrication of biodegradable polymers for drug delivery. Adv Drug Deliv Rev 56, 1621, 2004.
    • (2004) Adv Drug Deliv Rev , vol.56 , pp. 1621
    • Lu, Y.1    Chen, S.C.2
  • 30
    • 0035942280 scopus 로고    scopus 로고
    • The future of electronics manufacturing is revealed in the fine print
    • Nuzzo, R.G. The future of electronics manufacturing is revealed in the fine print. PNAS 98, 4827, 2001.
    • (2001) PNAS , vol.98 , pp. 4827
    • Nuzzo, R.G.1
  • 31
    • 65549135665 scopus 로고    scopus 로고
    • Alignment of skeletal muscle myoblasts and myotubes using linear micropatterned surfaces ground with abrasives
    • Shimizu, K., Fujita, H., and Nagamori, E. Alignment of skeletal muscle myoblasts and myotubes using linear micropatterned surfaces ground with abrasives. Biotechnol Bioeng 103, 631, 2009.
    • (2009) Biotechnol Bioeng , vol.103 , pp. 631
    • Shimizu, K.1    Fujita, H.2    Nagamori, E.3
  • 32
    • 33947703169 scopus 로고    scopus 로고
    • Processing methods of ultrathin poly(epsilon-caprolactone) films for tissue engineering applications
    • Tiaw, K.S., Teoh, S.H., Chen, R., and Hong, M.H. Processing methods of ultrathin poly(epsilon-caprolactone) films for tissue engineering applications. Biomacromolecules 8, 807, 2007.
    • (2007) Biomacromolecules , vol.8 , pp. 807
    • Tiaw, K.S.1    Teoh, S.H.2    Chen, R.3    Hong, M.H.4
  • 33
    • 67349269606 scopus 로고    scopus 로고
    • Nitric oxide production by endothelial cells derived from blood progenitors cultured on NaOH-treated polycaprolactone films: A biofunctionality study
    • Serrano, M.-C., Pagani, R., Vallet-Regí, M., Pen? a, J., Comas, J.-V., and Portoles, M.-T. Nitric oxide production by endothelial cells derived from blood progenitors cultured on NaOH-treated polycaprolactone films: a biofunctionality study. Acta Biomater 5, 2045, 2009.
    • (2009) Acta Biomater , vol.5 , pp. 2045
    • Serrano, M.-C.1    Pagani, R.2    Vallet-Regí, M.3    Pena, J.4    Comas, J.-V.5    Portoles, M.-T.6
  • 34
    • 59849114318 scopus 로고    scopus 로고
    • Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells
    • Zhang, Z.Y., Teoh, S.H., Chong, M.S., Schantz, J.T., Fisk, N.M., Choolani, M.A., and Chan, J. Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells 27, 126, 2009.
    • (2009) Stem Cells , vol.27 , pp. 126
    • Zhang, Z.Y.1    Teoh, S.H.2    Chong, M.S.3    Schantz, J.T.4    Fisk, N.M.5    Choolani, M.A.6    Chan, J.7
  • 36
    • 77950628103 scopus 로고    scopus 로고
    • Micropatterned matrix directs differentiation of human mesenchymal stem cells towards myocardial lineage
    • Tay, C.Y., Yu, H., Pal, M., Leong, W.S., Tan, N.S., Ng, K.W., Leong, D.T., and Tan, L.P. Micropatterned matrix directs differentiation of human mesenchymal stem cells towards myocardial lineage. Exp Cell Res 316, 1159, 2010.
    • (2010) Exp Cell Res , vol.316 , pp. 1159
    • Tay, C.Y.1    Yu, H.2    Pal, M.3    Leong, W.S.4    Tan, N.S.5    Ng, K.W.6    Leong, D.T.7    Tan, L.P.8
  • 37
    • 34347345884 scopus 로고    scopus 로고
    • Correlation of proliferation, morphology and biological responses of fibroblasts on LDPE with different surface wettability
    • Kim, S.H., Ha, H.J., Ko, Y.K., Yoon, S.J., Rhee, J.M., Kim, M.S., Lee, H.B., and Khang, G. Correlation of proliferation, morphology and biological responses of fibroblasts on LDPE with different surface wettability. J Biomater Sci Polym Ed 18, 609, 2007.
    • (2007) J Biomater Sci Polym Ed , vol.18 , pp. 609
    • Kim, S.H.1    Ha, H.J.2    Ko, Y.K.3    Yoon, S.J.4    Rhee, J.M.5    Kim, M.S.6    Lee, H.B.7    Khang, G.8
  • 38
    • 0033280680 scopus 로고    scopus 로고
    • Physical and microstructural effects of heat setting in polyester films
    • Greener, J., Tsou, A.H., and Blanton, T.N. Physical and microstructural effects of heat setting in polyester films. Polym Eng Sci 39, 2403, 1999.
    • (1999) Polym Eng Sci , vol.39 , pp. 2403
    • Greener, J.1    Tsou, A.H.2    Blanton, T.N.3
  • 40
    • 0036131454 scopus 로고    scopus 로고
    • Poissons ratio in linear viscoelasticity - A critical review
    • Tschoegl, N.W., Knauss, W.G., and Emri, I. Poissons ratio in linear viscoelasticity - a critical review. Mech Time Depend Mater 6, 3, 2002.
    • (2002) Mech Time Depend Mater , vol.6 , pp. 3
    • Tschoegl, N.W.1    Knauss, W.G.2    Emri, I.3
  • 41
    • 0001598685 scopus 로고
    • The modeling of multiaxial necking in polypropylene using a sliplink cross-link theory
    • Sweeney, J., and Ward, I.M. The modeling of multiaxial necking in polypropylene using a sliplink cross-link theory. J Rheol 39, 861, 1995.
    • (1995) J Rheol , vol.39 , pp. 861
    • Sweeney, J.1    Ward, I.M.2
  • 43
    • 0032768627 scopus 로고    scopus 로고
    • Apparent contact angles on rough surfaces: The Wenzel equation revisited
    • Wolansky, G., and Marmur, A. Apparent contact angles on rough surfaces: the Wenzel equation revisited. Colloid Surface A 156, 381, 1999.
    • (1999) Colloid Surface A , vol.156 , pp. 381
    • Wolansky, G.1    Marmur, A.2
  • 44
    • 45849113258 scopus 로고    scopus 로고
    • Electrospun PCL nanofibers with anisotropic mechanical properties as a biomedical scaffold
    • Kim, G.H. Electrospun PCL nanofibers with anisotropic mechanical properties as a biomedical scaffold. Biomed Mater 3, 025010, 2008.
    • (2008) Biomed Mater , vol.3 , pp. 025010
    • Kim, G.H.1
  • 45
    • 84855918446 scopus 로고    scopus 로고
    • The potential of human fetal mesenchymal stem cells for off-The-shelf bone tissue engineering application
    • Zhang, Z.Y., Teoh, S.H., Hui, J.H., Fisk, N.M., Choolani, M., and Chan, J.K. The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application. Biomaterials 33, 2656, 2012.
    • (2012) Biomaterials , vol.33 , pp. 2656
    • Zhang, Z.Y.1    Teoh, S.H.2    Hui, J.H.3    Fisk, N.M.4    Choolani, M.5    Chan, J.K.6
  • 46
    • 34548061232 scopus 로고    scopus 로고
    • Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning
    • Lim, J.Y., and Donahue, H.J. Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng 13, 1879, 2007.
    • (2007) Tissue Eng , vol.13 , pp. 1879
    • Lim, J.Y.1    Donahue, H.J.2
  • 47
    • 67349221548 scopus 로고    scopus 로고
    • Fibronectin modulates the morphology of osteoblast-like cells (MG-63) on nano-grooved substrates
    • Tsai, W.B., Ting, Y.C., Yang, J.Y., Lai, J.Y., and Liu, H.L. Fibronectin modulates the morphology of osteoblast-like cells (MG-63) on nano-grooved substrates. J Mater Sci Mater Med 20, 1367, 2009.
    • (2009) J Mater Sci Mater Med , vol.20 , pp. 1367
    • Tsai, W.B.1    Ting, Y.C.2    Yang, J.Y.3    Lai, J.Y.4    Liu, H.L.5
  • 48
    • 68549133138 scopus 로고    scopus 로고
    • Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients
    • Kim, D.H., Han, K., Gupta, K., Kwon, K.W., Suh, K.Y., and Levchenko, A. Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials 30, 5433, 2009.
    • (2009) Biomaterials , vol.30 , pp. 5433
    • Kim, D.H.1    Han, K.2    Gupta, K.3    Kwon, K.W.4    Suh, K.Y.5    Levchenko, A.6
  • 49
  • 50
    • 79957890620 scopus 로고    scopus 로고
    • Stacking of aligned cell sheets for layer-by-layer control of complex tissue structure
    • Williams, C., Xie, A.W., Yamato, M., Okano, T., and Wong, J.Y. Stacking of aligned cell sheets for layer-by-layer control of complex tissue structure. Biomaterials 32, 5625, 2011.
    • (2011) Biomaterials , vol.32 , pp. 5625
    • Williams, C.1    Xie, A.W.2    Yamato, M.3    Okano, T.4    Wong, J.Y.5
  • 51
    • 34047137919 scopus 로고    scopus 로고
    • Polarization of hippocampal neurons with competitive surface stimuli: Contact guidance cues are preferred over chemical ligands
    • Gomez, N., Chen, S.C., and Schmidt, C.E. Polarization of hippocampal neurons with competitive surface stimuli: contact guidance cues are preferred over chemical ligands. J R Soc Interface 4, 223, 2007.
    • (2007) J R Soc Interface , vol.4 , pp. 223
    • Gomez, N.1    Chen, S.C.2    Schmidt, C.E.3


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