Human Fetal Osteoblast Response on Poly(Methyl Methacrylate)/Polystyrene Demixed Thin Film Blends: Surface Chemistry Vs Topography Effects

Brian Meenan, Raechelle D'Sa, Peter Dickinson, Fiona Mccabe

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.
LanguageEnglish
JournalACS Applied Materials & Interfaces
Volumexxxx
DOIs
Publication statusPublished - 29 Dec 2015

Fingerprint

Polystyrenes
Osteoblasts
Polymethyl Methacrylate
Surface chemistry
Topography
Thin films
Polymer films
Biocompatible Materials
Materials science
Atmospheric pressure
Wetting
Polymers
Oxygen
Plasmas
Fabrication
Substrates
Chemical analysis

Keywords

  • surface topography
  • surface chemistry
  • polymer demixing
  • cellular response
  • human fetal osteoblasts
  • plasma surface modification

Cite this

@article{874753d98885448faf7d674b1ff82446,
title = "Human Fetal Osteoblast Response on Poly(Methyl Methacrylate)/Polystyrene Demixed Thin Film Blends: Surface Chemistry Vs Topography Effects",
abstract = "Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.",
keywords = "surface topography, surface chemistry, polymer demixing, cellular response, human fetal osteoblasts, plasma surface modification",
author = "Brian Meenan and Raechelle D'Sa and Peter Dickinson and Fiona Mccabe",
note = "Reference text: 1.Anselme, K.; Ploux, L.; Ponche, A.Cell/Material Interfaces: Influence of Surface Chemistry and Surface Topography on Cell Adhesion J. Adhes. Sci. Technol. 2010, 24, 831– 852, DOI: 10.1163/016942409X12598231568186 [CrossRef], [CAS] 2. Lord, M. S.; Foss, M.; Besenbacher, F.Influence of Nanoscale Surface Topography on Protein Adsorption and Cellular Response Nano Today 2010, 5, 66– 78, DOI: 10.1016/j.nantod.2010.01.001 [CrossRef], [CAS] 3. Lamers, E.; van Horssen, R.; te Riet, J.; van Delft, F.C.M.J.M.; Luttge, R.; Walboomers, X. F.; Jansen, J. A.The Influence of Nanoscale Topographical Cues on Initial Osteoblast Morphology and M Eur. Cells Mater. 2010, 20, 329– 343[PubMed], [CAS] 4. Biggs, M. J. P.; Richards, R. G.; Dalby, M. J.Nanotopographical Modification: A Regulator of Cellular Function Through Focal Adhesions Nanomedicine 2010, 6, 619– 633, DOI: 10.1016/j.nano.2010.01.009 [CrossRef], [PubMed], [CAS] 5. Kunzler, T. P.; Huwiler, C.; Drobek, T.; V{\"o}r{\"o}s, J.; Spencer, N. D.Systematic Study of Osteoblast Response to Nanotopography by Means of Nanoparticle-Density Gradients Biomaterials 2007, 28, 5000– 5006, DOI: 10.1016/j.biomaterials.2007.08.009 [CrossRef], [PubMed], [CAS] 6. Anselme, K.; Bigerelle, M.Role of Materials Surface Topography on Mammalian Cell Response Int. Mater. Rev. 2011, 56, 243– 266, DOI: 10.1179/1743280411Y.0000000001 [CrossRef], [CAS] 7. Yim, E. K. F.; Reano, R. M.; Pang, S. W.; Yee, A. F.; Chen, C. S.; Leong, K. W.Nanopattern-Induced Changes in Morphology and Motility of Smooth Muscle Cells Biomaterials 2005, 26, 5405– 5413, DOI: 10.1016/j.biomaterials.2005.01.058 [CrossRef], [PubMed], [CAS] 8. Affrossman, S.; Henn, G.; O’Neill, S. A.; Pethrick, R. A.; Stamm, M.Surface Topography and Composition of Deuterated Polystyrene-Poly (bromostyrene) Blends Macromolecules 1996, 29, 5010– 5016, DOI: 10.1021/ma9516910 [ACS Full Text ACS Full Text], [CAS] 9. Lim, J. Y.; Donahue, H. J.Cell Sensing and Response to Micro-and Nanostructured Surfaces Produced by Chemical and Topographic Patterning Tissue Eng. 2007, 13, 1879– 1891, DOI: 10.1089/ten.2006.0154 [CrossRef], [PubMed], [CAS] 10. Lim, J. Y.; Hansen, J. C.; Siedlecki, C. A.; Hengstebeck, R. W.; Cheng, J.; Winograd, N.; Donahue, H. J.Osteoblast Adhesion on Poly(l-lactic Acid)/Polystyrene Demixed Thin Film Blends: Effect of Nanotopography, Surface Chemistry, and Wettability Biomacromolecules 2005, 6, 3319– 3327, DOI: 10.1021/bm0503423 [ACS Full Text ACS Full Text], [PubMed], [CAS] 11. Lim, J. Y.; Hansen, J. C.; Siedlecki, C. A.; Runt, J.; Donahue, H. J.Human Foetal Osteoblastic Cell Response to Polymer-Demixed Nanotopographic Interfaces J. R. Soc., Interface 2005, 2, 97– 108, DOI: 10.1098/rsif.2004.0019 [CrossRef], [PubMed], [CAS] 12. Biggs, M. J. P.; Richards, R. G.; Dalby, M. J.Nanotopographical Modification: A Regulator of Cellular Function through Focal A dhesions Nanomedicine 2010, 6, 619– 633, DOI: 10.1016/j.nano.2010.01.009 [CrossRef], [PubMed], [CAS] 13. Dalby, M.; Giannaras, D.; Riehle, M.; Gadegaard, N.; Affrossman, S.; Curtis, A.Rapid Fibroblast Adhesion to 27nm High Polymer Demixed Nano-Topography Biomaterials 2004, 25, 77– 83, DOI: 10.1016/S0142-9612(03)00475-7 [CrossRef], [PubMed], [CAS] 14. Dalby, M.; Riehle, M.; Johnstone, H.; Affrossman, S.; Curtis, A.In Vitro Reaction of Endothelial Cells to Polymer Demixed Nanotopography Biomaterials 2002, 23, 2945– 2954, DOI: 10.1016/S0142-9612(01)00424-0 [CrossRef], [PubMed], [CAS] 15. Khattak, M.; Pu, F.; Curran, J. M.; Hunt, J. A.; D’Sa, R. A.Human Mesenchymal Stem Cell Response to Poly(ε-caprolactone/Poly(methyl methacrylate) Demixed Thin Films J. Mater. Sci.: Mater. Med. 2015, 26, 1– 7, DOI: 10.1007/s10856-015-5507-2 [CrossRef], [CAS] 16. Dalby, M. J.; Riehle, M. O.; Johnstone, H.; Affrossman, S.; Curtis, A. S. G.In Vitro Reaction of Endothelial Cells to Polymer Demixed Nanotopography Biomaterials 2002, 23, 2945– 2954, DOI: 10.1016/S0142-9612(01)00424-0 [CrossRef], [PubMed], [CAS] 17. Tanaka, K.; Takahara, A.; Kajiyama, T.Film Thickness Dependence of the Surface Structure of Immiscible Polystyrene/Poly(methyl methacrylate) Blends Macromolecules 1996, 29, 3232– 3239, DOI: 10.1021/ma951140+ [ACS Full Text ACS Full Text], [CAS] 18. Tanaka, K.; Takahara, A.; Kajiyama, T.Surface Molecular Aggregation Structure and Surface Molecular Motions of High-Molecular-Weight Polystyrene/Low-Molecular-Weight Poly(methyl methacrylate) Blend Films Macromolecules 1998, 31, 863– 869, DOI: 10.1021/ma9709866 [ACS Full Text ACS Full Text], [CAS] 19. Ton-That, C.; Shard, A.; Teare, D.; Bradley, R.XPS and AFM Surface Studies of Solvent-Cast PS/PMMA Blends Polymer 2001, 42, 1121– 1129, DOI: 10.1016/S0032-3861(00)00448-1 [CrossRef], [CAS] 20. Ton-That, C.; Shard, A. G.; Bradley, R. H.Surface Feature Size of Spin Cast PS/PMMA Blends Polymer 2002, 43, 4973– 4977, DOI: 10.1016/S0032-3861(02)00333-6 [CrossRef], [CAS] 21. Walheim, S.; B{\"o}ltau, M.; Mlynek, J.; Krausch, G.; Steiner, U.Structure Formation via Polymer Demixing in Spin-Cast Films Macromolecules 1997, 30, 4995– 5003, DOI: 10.1021/ma9619288 [ACS Full Text ACS Full Text], [CAS] 22. Heriot, S. Y.; Jones, R. A. L.An Interfacial Instability in a Transient Wetting Layer Leads to Lateral Phase Separation in Thin Spin-Cast Polymer-Blend Films Nat. Mater. 2005, 4, 782– 786, DOI: 10.1038/nmat1476 [CrossRef], [PubMed], [CAS] 23. Dekeyser, C.; Biltresse, S.; Marchand-Brynaert, J.; Rouxhet, P.; Dupont-Gillain, C. C.Submicrometer-Scale Heterogeneous Surfaces by PS–PMMA demixing Polymer 2004, 45, 2211– 2219, DOI: 10.1016/j.polymer.2004.01.045 [CrossRef], [CAS] 24. Ahn, D. U.; Wang, Z.; Campbell, I. P.; Stoykovich, M. P.; Ding, Y.Morphological Evolution of Thin PS/PMMA Films: Effects of Surface Energy and Blend Composition Polymer 2012, 53, 4187– 4194, DOI: 10.1016/j.polymer.2012.07.037 [CrossRef], [CAS] 25. D’Sa, R. A.; Burke, G. A.; Meenan, B. J.Protein Adhesion and Cell Response on Atmospheric Pressure Dielectric Barrier Discharge-Modified Polymer Surfaces Acta Biomater. 2010, 6, 2609– 2620, DOI: 10.1016/j.actbio.2010.01.015 [CrossRef], [PubMed], [CAS] 26. D’Sa, R. A.; Burke, G. A.; Meenan, B. J.Lens Epithelial Cell Response to Atmospheric Pressure Plasma Modified Poly(methylmethacrylate) Surfaces J. Mater. Sci.: Mater. Med. 2010, 21, 1703– 1712, DOI: 10.1007/s10856-010-4030-8 [CrossRef], [PubMed], [CAS] 27. D’Sa, R. A.; Dickinson, P. J.; Raj, J.; Pierscionek, B. K.; Meenan, B. J.Inhibition of Lens Epithelial Cell Growth via Immobilisation of Hyaluronic Acid on Atmospheric Pressure Plasma Modified Polystyrene Soft Matter 2011, 7, 608– 617, DOI: 10.1039/C0SM00936A [CrossRef], [CAS] 28. D’Sa, R. A.; Raj, J.; McMahon, M.; McDowell, D. A.; Burke, G. A.; Meenan, B. J.Atmospheric Pressure Plasma Induced Grafting of Poly(ethylene glycol) onto Silicone Elastomers for Controlling Biological Response J. Colloid Interface Sci. 2012, 375, 193– 202, DOI: 10.1016/j.jcis.2012.02.052 [CrossRef], [PubMed], [CAS] 29. D’Sa, R. A.; Meenan, B. J.Chemical Grafting of Poly (ethylene glycol) methyl ether methacrylate onto Polymer Surfaces by Atmospheric Pressure Plasma Processing Langmuir 2010, 26, 1894– 1903, DOI: 10.1021/la902654y [ACS Full Text ACS Full Text], [PubMed], [CAS] 30. Gengenbach, T. R.; Vasic, Z. R.; Chatelier, R. C.; Griesser, H. J.A Multi-Technique Study of the Spontaneous Oxidation of N-Hexane Plasma Polymers J. Polym. Sci., Part A: Polym. Chem. 1994, 32, 1399– 1414, DOI: 10.1002/pola.1994.080320801 [CrossRef], [CAS] 31. Kingshott, P.; Thissen, H.; Griesser, H. J.Effects of Cloud-Point Grafting, Chain Length, and Density of PEG Layers on Competitive Adsorption of Ocular Proteins Biomaterials 2002, 23, 2043– 2056, DOI: 10.1016/S0142-9612(01)00334-9 [CrossRef], [PubMed], [CAS] 32. Al-Omari, W. M.; Mitchell, C. A.; Cunningham, J. L.Surface Roughness and Wettability of Enamel and Dentine Surfaces Prepared with Different Dental Burs J. Oral Rehabil. 2001, 28, 645– 650, DOI: 10.1046/j.1365-2842.2001.00722.x [CrossRef], [PubMed], [CAS] 33. Bico, J.; Tordeux, C.; Qu{\'e}r{\'e}, D.Rough Wetting Europhys. Lett. 2001, 55, 214, DOI: 10.1209/epl/i2001-00402-x [CrossRef], [CAS] 34. Ton-That, C.; Shard, A. G.; Daley, R.; Bradley, R. H.Effects of Annealing on the Surface Composition and Morphology of PS/PMMA Blend Macromolecules 2000, 33, 8453– 8459, DOI: 10.1021/ma000792h [ACS Full Text ACS Full Text], [CAS] 35. Lim, J. Y.; Taylor, A. F.; Li, Z.; Vogler, E. A.; Donahue, H. J.Integrin Expression and Osteopontin Regulation in Human Fetal Osteoblastic Cells Mediated by Substratum Surface Characteristics Tissue Eng. 2005, 11, 19– 29, DOI: 10.1089/ten.2005.11.19 [CrossRef], [PubMed], [CAS] 36. Chen, C. S.; Alonso, J. L.; Ostuni, E.; Whitesides, G. M.; Ingber, D. E.Cell Shape provides Global Control of Focal Adhesion A ssembly Biochem. Biophys. Res. Commun. 2003, 307, 355– 361, DOI: 10.1016/S0006-291X(03)01165-3 [CrossRef], [PubMed], [CAS] 37. Ezzell, R. M.; Goldmann, W. H.; Wang, N.; Parasharama, N.; Ingber, D. E.Vinculin Promotes Cell Spreading by Mechanically Coupling Integrins to the Cytoskeleton Exp. Cell Res. 1997, 231, 14– 26, DOI: 10.1006/excr.1996.3451 [CrossRef], [PubMed], [CAS] 38. Oakley, C.; Brunette, D. M.Topographic Compensation: Guidance and Directed Locomotion of Fibroblasts on Grooved Micromachined Substrata in the Absence of Microtubules Cell Motil. Cytoskeleton 1995, 31, 45– 58, DOI: 10.1002/cm.970310106 [CrossRef], [PubMed], [CAS] 39. Lide, D. R.: CRC Handbook of Chemistry and Physics; CRC Press: Boca Raton, 2004. 40. Makoto, M.; Heng-Yong, N.; Wataru, M.; Hiroshi, T.Local Properties of Phase-Separated Polymer Surfaces by Force Microscopy Jpn. J. Appl. Phys. 1994, 33, 3775, DOI: 10.1143/JJAP.33.3775 [CrossRef] 41. Wu, S. Polymer Interface and Adhesion. Marcel Dekker: New York, 1982; Chapter 5. 42. Ton-That, C.; Shard, A.; Bradley, R.Surface Feature Size of Spin Cast PS/PMMA blends Polymer 2002, 43, 4973– 4977, DOI: 10.1016/S0032-3861(02)00333-6 [CrossRef], [CAS] 43. Jukes, P. C.; Heriot, S. Y.; Sharp, J. S.; Jones, R. A. L.Time-Resolved Light Scattering Studies of Phase Separation in Thin Film Semiconducting Polymer Blends during Spin-Coating Macromolecules 2005, 38, 2030– 2032, DOI: 10.1021/ma0477145 [ACS Full Text ACS Full Text], [CAS] 44. Emslie, A. G.; Bonner, F. T.; Peck, L. G.Flow of a Viscous Liquid on a Rotating Disk J. Appl. Phys. 1958, 29, 858– 862, DOI: 10.1063/1.1723300 [CrossRef], [CAS] 45. Borcia, G.; Anderson, C. A.; Brown, N. M. D.The Surface Oxidation of Selected Polymers using an Atmospheric Pressure Air Dielectric Barrier Discharge. Part II Appl. Surf. Sci. 2004, 225, 186– 197, DOI: 10.1016/j.apsusc.2003.10.002 [CrossRef], [CAS] 46. D’Sa, R. A. Surface Modification of Medically Relevant Polymers using Atmospheric Pressure Plasma Processing; University of Ulster: Ulster, U.K., 2008. 47. Liu, X.; Lim, J. Y.; Donahue, H. J.; Dhurjati, R.; Mastro, A. M.; Vogler, E. A.Influence of Substratum Surface Chemistry/Energy and Topography on the Human Fetal Osteoblastic Cell Line hFOB 1.19: Phenotypic and Genotypic Responses Observed In Vitro Biomaterials 2007, 28, 4535– 4550, DOI: 10.1016/j.biomaterials.2007.06.016 [CrossRef], [PubMed], [CAS] 48. Hendrich, C.; N{\"o}th, U.; Stahl, U.; Merklein, F.; Rader, C. P.; Sch{\"u}tze, N.; Thull, R.; Tuan, R. S.; Eulert, J.Testing of Skeletal Implant Surfaces with Human Fetal Osteoblasts Clin. Orthop. Relat. Res. 2002, 394, 278– 289, DOI: 10.1097/00003086-200201000-00033 [CrossRef], [PubMed] 49. Curran, J. M.; Chen, R.; Hunt, J. A.The Guidance of Human Mesenchymal Stem Cell Differentiation In Vitro by Controlled Modifications to the Cell Substrate Biomaterials 2006, 27, 4783– 4793, DOI: 10.1016/j.biomaterials.2006.05.001 [CrossRef], [PubMed], [CAS] 50. Curran, J. M.; Chen, R.; Hunt, J. A.Controlling the Phenotype and Function of Mesenchymal Stem Cells In Vitro by Adhesion to Silane-Modified Clean Glass Surfaces Biomaterials 2005, 26, 7057– 7067, DOI: 10.1016/j.biomaterials.2005.05.008 [CrossRef], [PubMed], [CAS] 51. Curran, J. M.; Stokes, R.; Irvine, E.; Graham, D.; Amro, N.; Sanedrin, R.; Jamil, H.; Hunt, J. A.Introducing Dip Pen Nanolithography as a Tool for Controlling Stem Cell Behaviour: Unlocking the Potential of the Next Generation of Smart Materials in Regenerative Medicine Lab Chip 2010, 10, 1662– 1670, DOI: 10.1039/c004149a [CrossRef], [PubMed], [CAS]",
year = "2015",
month = "12",
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language = "English",
volume = "xxxx",
journal = "ACS Applied Materials and Interfaces",
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Human Fetal Osteoblast Response on Poly(Methyl Methacrylate)/Polystyrene Demixed Thin Film Blends: Surface Chemistry Vs Topography Effects. / Meenan, Brian; D'Sa, Raechelle; Dickinson, Peter; Mccabe, Fiona.

In: ACS Applied Materials & Interfaces, Vol. xxxx, 29.12.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human Fetal Osteoblast Response on Poly(Methyl Methacrylate)/Polystyrene Demixed Thin Film Blends: Surface Chemistry Vs Topography Effects

AU - Meenan, Brian

AU - D'Sa, Raechelle

AU - Dickinson, Peter

AU - Mccabe, Fiona

N1 - Reference text: 1.Anselme, K.; Ploux, L.; Ponche, A.Cell/Material Interfaces: Influence of Surface Chemistry and Surface Topography on Cell Adhesion J. Adhes. Sci. Technol. 2010, 24, 831– 852, DOI: 10.1163/016942409X12598231568186 [CrossRef], [CAS] 2. Lord, M. S.; Foss, M.; Besenbacher, F.Influence of Nanoscale Surface Topography on Protein Adsorption and Cellular Response Nano Today 2010, 5, 66– 78, DOI: 10.1016/j.nantod.2010.01.001 [CrossRef], [CAS] 3. Lamers, E.; van Horssen, R.; te Riet, J.; van Delft, F.C.M.J.M.; Luttge, R.; Walboomers, X. F.; Jansen, J. A.The Influence of Nanoscale Topographical Cues on Initial Osteoblast Morphology and M Eur. Cells Mater. 2010, 20, 329– 343[PubMed], [CAS] 4. Biggs, M. J. P.; Richards, R. G.; Dalby, M. J.Nanotopographical Modification: A Regulator of Cellular Function Through Focal Adhesions Nanomedicine 2010, 6, 619– 633, DOI: 10.1016/j.nano.2010.01.009 [CrossRef], [PubMed], [CAS] 5. Kunzler, T. P.; Huwiler, C.; Drobek, T.; Vörös, J.; Spencer, N. D.Systematic Study of Osteoblast Response to Nanotopography by Means of Nanoparticle-Density Gradients Biomaterials 2007, 28, 5000– 5006, DOI: 10.1016/j.biomaterials.2007.08.009 [CrossRef], [PubMed], [CAS] 6. Anselme, K.; Bigerelle, M.Role of Materials Surface Topography on Mammalian Cell Response Int. Mater. Rev. 2011, 56, 243– 266, DOI: 10.1179/1743280411Y.0000000001 [CrossRef], [CAS] 7. Yim, E. K. F.; Reano, R. M.; Pang, S. W.; Yee, A. F.; Chen, C. S.; Leong, K. W.Nanopattern-Induced Changes in Morphology and Motility of Smooth Muscle Cells Biomaterials 2005, 26, 5405– 5413, DOI: 10.1016/j.biomaterials.2005.01.058 [CrossRef], [PubMed], [CAS] 8. Affrossman, S.; Henn, G.; O’Neill, S. A.; Pethrick, R. A.; Stamm, M.Surface Topography and Composition of Deuterated Polystyrene-Poly (bromostyrene) Blends Macromolecules 1996, 29, 5010– 5016, DOI: 10.1021/ma9516910 [ACS Full Text ACS Full Text], [CAS] 9. Lim, J. Y.; Donahue, H. J.Cell Sensing and Response to Micro-and Nanostructured Surfaces Produced by Chemical and Topographic Patterning Tissue Eng. 2007, 13, 1879– 1891, DOI: 10.1089/ten.2006.0154 [CrossRef], [PubMed], [CAS] 10. Lim, J. Y.; Hansen, J. C.; Siedlecki, C. A.; Hengstebeck, R. W.; Cheng, J.; Winograd, N.; Donahue, H. J.Osteoblast Adhesion on Poly(l-lactic Acid)/Polystyrene Demixed Thin Film Blends: Effect of Nanotopography, Surface Chemistry, and Wettability Biomacromolecules 2005, 6, 3319– 3327, DOI: 10.1021/bm0503423 [ACS Full Text ACS Full Text], [PubMed], [CAS] 11. Lim, J. Y.; Hansen, J. C.; Siedlecki, C. A.; Runt, J.; Donahue, H. J.Human Foetal Osteoblastic Cell Response to Polymer-Demixed Nanotopographic Interfaces J. R. Soc., Interface 2005, 2, 97– 108, DOI: 10.1098/rsif.2004.0019 [CrossRef], [PubMed], [CAS] 12. Biggs, M. J. P.; Richards, R. G.; Dalby, M. J.Nanotopographical Modification: A Regulator of Cellular Function through Focal A dhesions Nanomedicine 2010, 6, 619– 633, DOI: 10.1016/j.nano.2010.01.009 [CrossRef], [PubMed], [CAS] 13. Dalby, M.; Giannaras, D.; Riehle, M.; Gadegaard, N.; Affrossman, S.; Curtis, A.Rapid Fibroblast Adhesion to 27nm High Polymer Demixed Nano-Topography Biomaterials 2004, 25, 77– 83, DOI: 10.1016/S0142-9612(03)00475-7 [CrossRef], [PubMed], [CAS] 14. Dalby, M.; Riehle, M.; Johnstone, H.; Affrossman, S.; Curtis, A.In Vitro Reaction of Endothelial Cells to Polymer Demixed Nanotopography Biomaterials 2002, 23, 2945– 2954, DOI: 10.1016/S0142-9612(01)00424-0 [CrossRef], [PubMed], [CAS] 15. Khattak, M.; Pu, F.; Curran, J. M.; Hunt, J. A.; D’Sa, R. A.Human Mesenchymal Stem Cell Response to Poly(ε-caprolactone/Poly(methyl methacrylate) Demixed Thin Films J. Mater. Sci.: Mater. Med. 2015, 26, 1– 7, DOI: 10.1007/s10856-015-5507-2 [CrossRef], [CAS] 16. Dalby, M. J.; Riehle, M. O.; Johnstone, H.; Affrossman, S.; Curtis, A. S. G.In Vitro Reaction of Endothelial Cells to Polymer Demixed Nanotopography Biomaterials 2002, 23, 2945– 2954, DOI: 10.1016/S0142-9612(01)00424-0 [CrossRef], [PubMed], [CAS] 17. Tanaka, K.; Takahara, A.; Kajiyama, T.Film Thickness Dependence of the Surface Structure of Immiscible Polystyrene/Poly(methyl methacrylate) Blends Macromolecules 1996, 29, 3232– 3239, DOI: 10.1021/ma951140+ [ACS Full Text ACS Full Text], [CAS] 18. Tanaka, K.; Takahara, A.; Kajiyama, T.Surface Molecular Aggregation Structure and Surface Molecular Motions of High-Molecular-Weight Polystyrene/Low-Molecular-Weight Poly(methyl methacrylate) Blend Films Macromolecules 1998, 31, 863– 869, DOI: 10.1021/ma9709866 [ACS Full Text ACS Full Text], [CAS] 19. Ton-That, C.; Shard, A.; Teare, D.; Bradley, R.XPS and AFM Surface Studies of Solvent-Cast PS/PMMA Blends Polymer 2001, 42, 1121– 1129, DOI: 10.1016/S0032-3861(00)00448-1 [CrossRef], [CAS] 20. Ton-That, C.; Shard, A. G.; Bradley, R. H.Surface Feature Size of Spin Cast PS/PMMA Blends Polymer 2002, 43, 4973– 4977, DOI: 10.1016/S0032-3861(02)00333-6 [CrossRef], [CAS] 21. Walheim, S.; Böltau, M.; Mlynek, J.; Krausch, G.; Steiner, U.Structure Formation via Polymer Demixing in Spin-Cast Films Macromolecules 1997, 30, 4995– 5003, DOI: 10.1021/ma9619288 [ACS Full Text ACS Full Text], [CAS] 22. Heriot, S. Y.; Jones, R. A. L.An Interfacial Instability in a Transient Wetting Layer Leads to Lateral Phase Separation in Thin Spin-Cast Polymer-Blend Films Nat. Mater. 2005, 4, 782– 786, DOI: 10.1038/nmat1476 [CrossRef], [PubMed], [CAS] 23. Dekeyser, C.; Biltresse, S.; Marchand-Brynaert, J.; Rouxhet, P.; Dupont-Gillain, C. C.Submicrometer-Scale Heterogeneous Surfaces by PS–PMMA demixing Polymer 2004, 45, 2211– 2219, DOI: 10.1016/j.polymer.2004.01.045 [CrossRef], [CAS] 24. Ahn, D. U.; Wang, Z.; Campbell, I. P.; Stoykovich, M. P.; Ding, Y.Morphological Evolution of Thin PS/PMMA Films: Effects of Surface Energy and Blend Composition Polymer 2012, 53, 4187– 4194, DOI: 10.1016/j.polymer.2012.07.037 [CrossRef], [CAS] 25. D’Sa, R. A.; Burke, G. A.; Meenan, B. J.Protein Adhesion and Cell Response on Atmospheric Pressure Dielectric Barrier Discharge-Modified Polymer Surfaces Acta Biomater. 2010, 6, 2609– 2620, DOI: 10.1016/j.actbio.2010.01.015 [CrossRef], [PubMed], [CAS] 26. D’Sa, R. A.; Burke, G. A.; Meenan, B. J.Lens Epithelial Cell Response to Atmospheric Pressure Plasma Modified Poly(methylmethacrylate) Surfaces J. Mater. Sci.: Mater. Med. 2010, 21, 1703– 1712, DOI: 10.1007/s10856-010-4030-8 [CrossRef], [PubMed], [CAS] 27. D’Sa, R. A.; Dickinson, P. J.; Raj, J.; Pierscionek, B. K.; Meenan, B. J.Inhibition of Lens Epithelial Cell Growth via Immobilisation of Hyaluronic Acid on Atmospheric Pressure Plasma Modified Polystyrene Soft Matter 2011, 7, 608– 617, DOI: 10.1039/C0SM00936A [CrossRef], [CAS] 28. D’Sa, R. A.; Raj, J.; McMahon, M.; McDowell, D. A.; Burke, G. A.; Meenan, B. J.Atmospheric Pressure Plasma Induced Grafting of Poly(ethylene glycol) onto Silicone Elastomers for Controlling Biological Response J. Colloid Interface Sci. 2012, 375, 193– 202, DOI: 10.1016/j.jcis.2012.02.052 [CrossRef], [PubMed], [CAS] 29. D’Sa, R. A.; Meenan, B. J.Chemical Grafting of Poly (ethylene glycol) methyl ether methacrylate onto Polymer Surfaces by Atmospheric Pressure Plasma Processing Langmuir 2010, 26, 1894– 1903, DOI: 10.1021/la902654y [ACS Full Text ACS Full Text], [PubMed], [CAS] 30. Gengenbach, T. R.; Vasic, Z. R.; Chatelier, R. C.; Griesser, H. J.A Multi-Technique Study of the Spontaneous Oxidation of N-Hexane Plasma Polymers J. Polym. Sci., Part A: Polym. Chem. 1994, 32, 1399– 1414, DOI: 10.1002/pola.1994.080320801 [CrossRef], [CAS] 31. Kingshott, P.; Thissen, H.; Griesser, H. J.Effects of Cloud-Point Grafting, Chain Length, and Density of PEG Layers on Competitive Adsorption of Ocular Proteins Biomaterials 2002, 23, 2043– 2056, DOI: 10.1016/S0142-9612(01)00334-9 [CrossRef], [PubMed], [CAS] 32. Al-Omari, W. M.; Mitchell, C. A.; Cunningham, J. L.Surface Roughness and Wettability of Enamel and Dentine Surfaces Prepared with Different Dental Burs J. Oral Rehabil. 2001, 28, 645– 650, DOI: 10.1046/j.1365-2842.2001.00722.x [CrossRef], [PubMed], [CAS] 33. Bico, J.; Tordeux, C.; Quéré, D.Rough Wetting Europhys. Lett. 2001, 55, 214, DOI: 10.1209/epl/i2001-00402-x [CrossRef], [CAS] 34. Ton-That, C.; Shard, A. G.; Daley, R.; Bradley, R. H.Effects of Annealing on the Surface Composition and Morphology of PS/PMMA Blend Macromolecules 2000, 33, 8453– 8459, DOI: 10.1021/ma000792h [ACS Full Text ACS Full Text], [CAS] 35. Lim, J. Y.; Taylor, A. F.; Li, Z.; Vogler, E. A.; Donahue, H. J.Integrin Expression and Osteopontin Regulation in Human Fetal Osteoblastic Cells Mediated by Substratum Surface Characteristics Tissue Eng. 2005, 11, 19– 29, DOI: 10.1089/ten.2005.11.19 [CrossRef], [PubMed], [CAS] 36. Chen, C. S.; Alonso, J. L.; Ostuni, E.; Whitesides, G. M.; Ingber, D. E.Cell Shape provides Global Control of Focal Adhesion A ssembly Biochem. Biophys. Res. Commun. 2003, 307, 355– 361, DOI: 10.1016/S0006-291X(03)01165-3 [CrossRef], [PubMed], [CAS] 37. Ezzell, R. M.; Goldmann, W. H.; Wang, N.; Parasharama, N.; Ingber, D. E.Vinculin Promotes Cell Spreading by Mechanically Coupling Integrins to the Cytoskeleton Exp. Cell Res. 1997, 231, 14– 26, DOI: 10.1006/excr.1996.3451 [CrossRef], [PubMed], [CAS] 38. Oakley, C.; Brunette, D. M.Topographic Compensation: Guidance and Directed Locomotion of Fibroblasts on Grooved Micromachined Substrata in the Absence of Microtubules Cell Motil. Cytoskeleton 1995, 31, 45– 58, DOI: 10.1002/cm.970310106 [CrossRef], [PubMed], [CAS] 39. Lide, D. R.: CRC Handbook of Chemistry and Physics; CRC Press: Boca Raton, 2004. 40. Makoto, M.; Heng-Yong, N.; Wataru, M.; Hiroshi, T.Local Properties of Phase-Separated Polymer Surfaces by Force Microscopy Jpn. J. Appl. Phys. 1994, 33, 3775, DOI: 10.1143/JJAP.33.3775 [CrossRef] 41. Wu, S. Polymer Interface and Adhesion. Marcel Dekker: New York, 1982; Chapter 5. 42. Ton-That, C.; Shard, A.; Bradley, R.Surface Feature Size of Spin Cast PS/PMMA blends Polymer 2002, 43, 4973– 4977, DOI: 10.1016/S0032-3861(02)00333-6 [CrossRef], [CAS] 43. Jukes, P. C.; Heriot, S. Y.; Sharp, J. S.; Jones, R. A. L.Time-Resolved Light Scattering Studies of Phase Separation in Thin Film Semiconducting Polymer Blends during Spin-Coating Macromolecules 2005, 38, 2030– 2032, DOI: 10.1021/ma0477145 [ACS Full Text ACS Full Text], [CAS] 44. Emslie, A. G.; Bonner, F. T.; Peck, L. G.Flow of a Viscous Liquid on a Rotating Disk J. Appl. Phys. 1958, 29, 858– 862, DOI: 10.1063/1.1723300 [CrossRef], [CAS] 45. Borcia, G.; Anderson, C. A.; Brown, N. M. D.The Surface Oxidation of Selected Polymers using an Atmospheric Pressure Air Dielectric Barrier Discharge. Part II Appl. Surf. Sci. 2004, 225, 186– 197, DOI: 10.1016/j.apsusc.2003.10.002 [CrossRef], [CAS] 46. D’Sa, R. A. Surface Modification of Medically Relevant Polymers using Atmospheric Pressure Plasma Processing; University of Ulster: Ulster, U.K., 2008. 47. Liu, X.; Lim, J. Y.; Donahue, H. J.; Dhurjati, R.; Mastro, A. M.; Vogler, E. A.Influence of Substratum Surface Chemistry/Energy and Topography on the Human Fetal Osteoblastic Cell Line hFOB 1.19: Phenotypic and Genotypic Responses Observed In Vitro Biomaterials 2007, 28, 4535– 4550, DOI: 10.1016/j.biomaterials.2007.06.016 [CrossRef], [PubMed], [CAS] 48. Hendrich, C.; Nöth, U.; Stahl, U.; Merklein, F.; Rader, C. P.; Schütze, N.; Thull, R.; Tuan, R. S.; Eulert, J.Testing of Skeletal Implant Surfaces with Human Fetal Osteoblasts Clin. Orthop. Relat. Res. 2002, 394, 278– 289, DOI: 10.1097/00003086-200201000-00033 [CrossRef], [PubMed] 49. Curran, J. M.; Chen, R.; Hunt, J. A.The Guidance of Human Mesenchymal Stem Cell Differentiation In Vitro by Controlled Modifications to the Cell Substrate Biomaterials 2006, 27, 4783– 4793, DOI: 10.1016/j.biomaterials.2006.05.001 [CrossRef], [PubMed], [CAS] 50. Curran, J. M.; Chen, R.; Hunt, J. A.Controlling the Phenotype and Function of Mesenchymal Stem Cells In Vitro by Adhesion to Silane-Modified Clean Glass Surfaces Biomaterials 2005, 26, 7057– 7067, DOI: 10.1016/j.biomaterials.2005.05.008 [CrossRef], [PubMed], [CAS] 51. Curran, J. M.; Stokes, R.; Irvine, E.; Graham, D.; Amro, N.; Sanedrin, R.; Jamil, H.; Hunt, J. A.Introducing Dip Pen Nanolithography as a Tool for Controlling Stem Cell Behaviour: Unlocking the Potential of the Next Generation of Smart Materials in Regenerative Medicine Lab Chip 2010, 10, 1662– 1670, DOI: 10.1039/c004149a [CrossRef], [PubMed], [CAS]

PY - 2015/12/29

Y1 - 2015/12/29

N2 - Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.

AB - Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.

KW - surface topography

KW - surface chemistry

KW - polymer demixing

KW - cellular response

KW - human fetal osteoblasts

KW - plasma surface modification

U2 - 10.1021/acsami.5b08073

DO - 10.1021/acsami.5b08073

M3 - Article

VL - xxxx

JO - ACS Applied Materials and Interfaces

T2 - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

SN - 1944-8244

ER -