Modulating the biocompatibility of polymer surfaces with poly(ethylene glycol): effect of fibronectin.

A novel approach described earlier for improving polymer substratum biocompatibility(1) is further elucidated. Polysulfone (PSf) spin-coating films were modified by covalent end-on grafting of hydrophilic and sterically demanding photo-reactive poly(ethylene glycol) (PEG) conjugates (ABMPEG; 10 kDa). The degree of grafting density was varied systematically, yielding a wide spectrum of attained surface characteristics monitored by air-water contact angles (captive bubble method). Fibronectin (FN) adsorption was studied by in situ ellipsometry and found to decrease monotonically as ABMPEG grafting density increased. The adhesive interaction of human skin fibroblasts with these substrata and, in particular, the effect of FN precoating were investigated in detail. A clear optimum of cell-substratum interactions was found for mildly modified substrata, employing well established microscopic and immunofluorescence techniques, namely the monitoring of cell adhesion and spreading, overall cell morphology, organization of FN receptors, and focal adhesions as well as FN matrix formation. The results suggest that cell interactions with hydrophobic polymer substrata are enhanced considerably when modified with hydrophilic and sterically demanding PEG moieties at a low surface coverage due to enhanced biologic activity of adsorbed and intercalated adhesive proteins such as FN.

[1]  Katja Jankova,et al.  Optimizing Cell−Surface Interactions by Photografting of Poly(ethylene glycol) , 2000 .

[2]  M. Ulbricht,et al.  Synthesis of photoreactive α‐4‐azidobenzoyl‐ω‐methoxy‐poly(ethylene glycol)s and their end‐on photo‐grafting onto polysulfone ultrafiltration membranes , 1998 .

[3]  P. Tresco,et al.  Relative importance of surface wettability and charged functional groups on NIH 3T3 fibroblast attachment, spreading, and cytoskeletal organization. , 1998, Journal of biomedical materials research.

[4]  Premnath,et al.  Poly(ethylene oxide) Grafted to Silicon Surfaces: Grafting Density and Protein Adsorption. , 1998, Macromolecules.

[5]  P. Tresco,et al.  A novel method for surface modification to promote cell attachment to hydrophobic substrates. , 1998, Journal of biomedical materials research.

[6]  L. Griffith,et al.  Microdistribution of substratum-bound ligands affects cell function: hepatocyte spreading on PEO-tethered galactose. , 1998, Biomaterials.

[7]  M. Ferrari,et al.  Proteins and cells on PEG immobilized silicon surfaces. , 1998, Biomaterials.

[8]  P Rolfe,et al.  Physical and biological properties of compound membranes incorporating a copolymer with a phosphorylcholine head group. , 1998, Biomaterials.

[9]  F Bittinger,et al.  Current trends in biocompatibility testing , 1998, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[10]  T. Groth,et al.  Studies on cell-biomaterial interaction: role of tyrosine phosphorylation during fibroblast spreading on surfaces varying in wettability. , 1996, Biomaterials.

[11]  F. Grinnell,et al.  Studies on the biocompatibility of materials: fibroblast reorganization of substratum-bound fibronectin on surfaces varying in wettability. , 1996, Journal of biomedical materials research.

[12]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[13]  J. Jansen,et al.  Effect of parallel surface microgrooves and surface energy on cell growth. , 1995, Journal of biomedical materials research.

[14]  T. Groth,et al.  Reorganization of substratum-bound fibronectin on hydrophilic and hydrophobic materials is related to biocompatibility , 1994 .

[15]  John Calvin Reed,et al.  Anchorage dependence, integrins, and apoptosis , 1994, Cell.

[16]  G. Truskey,et al.  Effect of the conformation and orientation of adsorbed fibronectin on endothelial cell spreading and the strength of adhesion. , 1993, Journal of biomedical materials research.

[17]  S. Haskill,et al.  Signal transduction from the extracellular matrix , 1993, The Journal of cell biology.

[18]  A S Hoffman,et al.  Influence of the substrate binding characteristics of fibronectin on corneal epithelial cell outgrowth. Student Research Award in the Doctoral Degree Candidate Category, Fourth World Biomaterials Congress (18th annual meeting of the Society for Biomaterials), Berlin, Germany, April 24-28, 1992. , 1992, Journal of biomedical materials research.

[19]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[20]  J. Hubbell,et al.  An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3- mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation , 1991, The Journal of cell biology.

[21]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  P. Galletti.  Thrombosis in Extracorporeal Devices , 1987, Annals of the New York Academy of Sciences.

[23]  F. Grinnell.  Focal adhesion sites and the removal of substratum-bound fibronectin , 1986, The Journal of cell biology.

[24]  J. Feijen,et al.  Interaction of cultured human endothelial cells with polymeric surfaces of different wettabilities. , 1985, Biomaterials.

[25]  F. Grinnell,et al.  Adsorption characteristics of plasma fibronectin in relationship to biological activity. , 1981, Journal of biomedical materials research.

[26]  F. Grinnell,et al.  Atachment of normal and transformed hamster kidney cells to substrata varying in chemical composition. , 1973, Biochemical medicine.

[27]  B. Haye,et al.  cAMP levels in cells attached to AN69 and Cuprophan: cAMP dependence of cell aggregation and the influence of serum. , 1999, Biomaterials.

[28]  Y. Ito,et al.  Artificial juxtacrine stimulation for tissue engineering. , 1998, Journal of biomaterials science. Polymer edition.

[29]  T. Groth,et al.  Morphological evidence for a different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata. , 1997, Journal of biomaterials science. Polymer edition.

[30]  J. A. Hubbell,et al.  Surface Treatments of Polymers for Biocompatibility , 1996 .

[31]  E. Ruoslahti,et al.  Integrin signaling and matrix assembly. , 1996, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[32]  Joseph D. Andrade,et al.  Blood compatibility of polyethylene oxide surfaces , 1995 .

[33]  Kinam Park,et al.  Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity. , 1993, Journal of biomaterials science. Polymer edition.

[34]  C. R. Howlett,et al.  Attachment of human bone cells to tissue culture polystyrene and to unmodified polystyrene: the effect of surface chemistry upon initial cell attachment. , 1993, Journal of biomaterials science. Polymer edition.

[35]  R. Azzam,et al.  Ellipsometry and polarized light , 1977 .