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Effects of the Chemical Structure and the Surface Properties of Polymeric Biomaterials on Their Biocompatibility

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Abstract

Polymeric biomaterials have extensively been used in medicinal applications. However, factors that determine their biocompatibility are still not very clear. This article reviews various effects of the chemical structure and the surface properties of polymeric biomaterials on their biocompatibility, including protein adsorption, cell adhesion, cytotoxicity, blood compatibility, and tissue compatibility. Understanding these aspects of biocompatibility is important to the improvement of the biocompatibility of existing polymers and the design of new biocompatible polymers.

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REFERENCES

  1. J. B. Park. Biomaterials. In J.D. Bronzino (ed.), Biomedical Engineering Handbook,CRC Press and IEEE Press, 1995, pp. 530–610.

  2. S. H. Teoh, Z. H. Tang, and G. W. Hastings. Thermoplastic polymers in biomedical applications: structure, properties and processing. In J. Black and G. Hastings (eds.), Handbook of Biomaterial Properties, Chapman & Hall, London, 1998, pp. 270–301.

    Google Scholar 

  3. J. Jagur-Grodzinski. Biomedical application of functional polymers. Reactive & Fuctional Polymers 39:99–138 (1999).

    Google Scholar 

  4. D. F. Williams. Biocompatibility of Clinical Implant Materials, Vol. II, CRC Press, Boca Raton, FL, 1981.

    Google Scholar 

  5. H. Park and K. Park. Pharm. Res. { vn13}:1770–1776 (1996).

  6. C. J. Kirkpatrick, F. Bittinger, M. Wagner, H. Kohler, T. G. van Kooten, C. L. Klein, and M. Otto. Current trends in biocompatibility testing. J. Eng. Med. { vn212}:75–84 (1998).

    Google Scholar 

  7. D. Sgouras and R. Duncan. Methods for the evaluation of biocompatibility of soluble synthetic polymers which have potential for biomedical use: 1-use of the tetrazolium-based colorimetric assay (MTT) as a preliminary screen for evaluation of in vitro cytotoxicity. J. Mater. Sci: Mater. Med. 1:61–68 (1990).

    Google Scholar 

  8. J. Vienken, M. Diamantoglou, C. Hahn, H. Kamusewitz, and D. Paul. Considerations on developmental aspects of biocompatible dialysis membranes. Artif. Organs { vn19}:398–406 (1995).

    Google Scholar 

  9. E. Ruckenstein and S. V. Gourisankar. Preparation and characterization of thin film surface coatings for biological environments. Biomaterials 7:403–422 (1986).

    Google Scholar 

  10. J. D. Andrade. Interfacial phenomena and biomaterials. Med. Instrum. { vn7}:110–120 (1973).

    Google Scholar 

  11. D. H. Kaelble and K. C. Uy. A reinterpretation of organic liquid-polytetrafluoroethylene surface interaction. J. Adhesion { vn2}: 50–60 (1970).

    Google Scholar 

  12. D. R. Lu and K. Park. Protein adsorption on polymer surfaces: calculation of adsorption energies. J. Biomater. Sci. Polym. Ed. { vn1}:243–260 (1990).

    Google Scholar 

  13. J. M. Schakenraad, H. I. Busscher, C. R. H. Wildevuur, and J. Arends. The influence of substratum surface free energy on spreading of various cell-types on polymers. Adv. Biomater. { vn6}: 263–268 (1986).

    Google Scholar 

  14. J. M. Schakenraad. J. Arends, H. I. Busscher, F. Dijk, P. B. Wachem, and C. R. H. Wildevuur. Kinetics of cell spreading on protein precoated substrata: a study of interfacial aspects. Biomaterials { vn10}:43–50 (1989).

    Google Scholar 

  15. J. Jagur-Grodzinski. Heterogeneous Modification of Polymers, Wiley, Chichester, 1997.

  16. B. D. Ratner and D. G. Castner. Surface Modification of Polymeric Biomaterials,New York, Plenum Press, 1997.

    Google Scholar 

  17. K. Esumi, A. M. Schwartz, and A. C. Zettlemoyer. Effects of ultra-violet radiation on polymer surfaces. J. Coll. Interface Sci. { vn95}:102–107 (1983).

    Google Scholar 

  18. A. A. Benderley. Treatment of Teflon to promote bondability. J. Appl. Polymer. Sci. { vn6}:221–225 (1962).

    Google Scholar 

  19. A. S. Hoffman. J Appl Polym Sci. Appl Polym Symp { vn4vn2}:251–259 (1988).

    Google Scholar 

  20. G. H. Hsiue, S. D. Lee, C. C. Wang, H. M. I. Shiue, and P. C. T. Chang. Plasma-induced graft copolymerization of HEMA onto silicon rubber and TPX film improving rabbit corneal epithelial cell attachment and growth. Biomaterials { vn15}:163–171 (1994).

    Google Scholar 

  21. B. D. Ratner, A. S. Hoffman, S. R. Hanson, L. A. Harker, and J. D. Whiffen. J Polym Sci Polym Symp { vn66}:363–372 (1979).

    Google Scholar 

  22. A. A. A. de Queiroz, E. R. Barrak, and S. C. de Castro. Thermodynamic analysis of the surface of biomaterials. J. Mol. Struct. { vn394}:271–279 (1997).

    Google Scholar 

  23. D. A. Puleo and A. Nanci. Understanding and controlling the bone-implant interface. Biomaterials { vn20}:2311–2321 (1999).

    Google Scholar 

  24. R. E. Baier and A. E. Meyer. Implant surface preparation. Int. J. Oral Maxillofac. Implants { vn3}:9–20 (1988).

    Google Scholar 

  25. J. D. Andrade. Principles of protein adsorption. In J.D. Andrade (ed.), Surface and Interfacial Aspects of Biomedical Polymer, New York, Plenum, 1985, pp1–80.

    Google Scholar 

  26. J. L. Brash and T. A. Horbett. In J.L. Brash and T.A. Horbett (eds.), Proteins at Interface Physicochemical and Biochemical Studies, Vol. 343, Washington, DC, ACS Symposium Series, 1987, pp. 1–33.

  27. D. L. Elbert and J. A Hubbell, Surface treatments of polymers for biocompatibility. Annu Rev Mater Sci { vn26}:365–394 (1996).

    Google Scholar 

  28. T. Akaike, T. Okano, M. Terano, and N. Yui. Advances in Polymeric Biomaterials Sciences, Tokyo, CMC Co. Ltd, 1997.

    Google Scholar 

  29. A. Higuchi, K. Shirano, M. Harashima, B. O. Yoon, M. Hara, M. Hattori, and K. Imamura. Chemically modified polysulfone hollow fibers with vinylpyrrolidone having improved blood compatibility. Biomaterials { vn23}:2659–2666 (2002).

    Google Scholar 

  30. P. D. Nair, M. Jayabalan, and V. N. Krishnamurthy. Polyurethane-polyacrylamide IPNs. I. Synthesis and characterization. J. Polym. Sci. Part A: Polym. Chem. { vn28}:3775–3786 (1990).

    Google Scholar 

  31. D. S. Jones, M. C. Bonner, S. P. Gorman, M. Akay, and P. F. Keane. Sequential polyurethane-poly(methylmethacrylate) interpenetrating polymer networks as ureteral biomaterials: mechanical properties and comparative resistance to urinary encrustation. J. Mater. Sci. Mater. Med. { vn8}:713–717 (1997).

    Google Scholar 

  32. G. A. Abraham, A. A. A. de Queiroz, and J. S. Roman. Hydrophilic hybrid IPNs of segmented polyurethanes and copolymers of vinylpyrrolidone for applications in medicine. Biomaterials { vn22}:1971–1985 (2001).

    Google Scholar 

  33. T. A. Horbett and J. L. Brash. Proteins at Interfaces. II. Fundamental and Application, Vol. 602, Washington, DC, ACS Symposium Series, 1995.

  34. E. K. Yeh, J. Newman, and C. J. Radke. Equilibrium configurations of liquid droplets on solid surfaces under the influence of thin-film forces, Part 1. Thermodynamics. Colloids and Surfaces A: Physicochemical and Engineering Aspect { vn156}:137–144 (1999).

    Google Scholar 

  35. C. J. Beverung, C. J. Radke, and H. W. Blanch. Adsorption dynamics of L-glutamic acid copolymers at a heptane/water surface. Biophys. Chem. { vn7}0:121–132 (1998).

    Google Scholar 

  36. D. T. Kim, H. W. Blanch, and C. J. Radke. Direct imaging of lysozyme adsorption onto mica by atomic force microscope. Langmuir { vn18}:5841–5850 (2002).

    Google Scholar 

  37. M. Tanaka, T. Motomura, M. Kawada, T. Anzai, Y. Kasori, T. Shiroya, K. Shimura, M. Onishi, and A. Mochizuki. Blood compatible aspects of poly(2-methoxyethylacrylate) (PMEA)-Relationship between protein adsorption and platelet adhesion on PMEA surface. Biomaterials { vn21}:1471–1481 (2000).

    Google Scholar 

  38. D. R. Absolom, W. Zingg, Z. Policova, and A. W. Newmann. Determination of surface tension of protein-coated materials by means of the advancing solidification front technique. Trans. Am. Soc. Artif. Org. { vn29}:146–151 (1983).

    Google Scholar 

  39. S. Meumer, H. F. G. Heijnen, M. J. W. Ijsseldijk, E. Orlando, P. G. de Groot, and J. J. Sixma. Pletelet adhesion to fibronectin in flow: the importance of von Willebrand factor and glycoprotein Ib. Blood 86:3452–3460 (1995).

    Google Scholar 

  40. S. Nagaoka and R. Akashi. Low friction hydrophilic surface for medical devices. J. Bioact. Compat. Polymers { vn5}:212–246 (1990).

    Google Scholar 

  41. J. H. Lee and H. B. Lee. Platelet adhesion onto wettability gradient surfaces in the absence and presence of plasma proteins. J. Biomed. Mater. Res. { vn41}:304–311 (1998).

    Google Scholar 

  42. H. J. Lee, J. Kopecek, and J. D. Andrade. Protein resistant surface prepared by PEO containing block copolymer surfactant. J. Biomed. Mater. Res. { vn23}:351–368 (1989).

    Google Scholar 

  43. T. Matsuda and S. Ito. Surface coating of hydrophilichydrophobic block co-polymers on a poly(acrylonitrile) haemodialyser reduce platelet adhesion and its transmembrane stimulation. Biomaterials { vn15}:417–422 (1994).

    Google Scholar 

  44. B. Seijo, E. Fattal, L. R. Treupel, and P. Couvreur. Design of nanoparticles of less than 50 nm diameter: preparation, characterization and loading. Int. J. Pharm. { vn62}:1–7 (1990).

    Google Scholar 

  45. E. Hamad and S. Qutubuddin. Theory of micelle formation by amphiphililic side-chain polymers. Macromolecules { vn23}:4185–4191 (1990).

    Google Scholar 

  46. M. Malmsten and B. Lindman. Self-assembly in aqueous block copolymer solutions. Macromolecules { vn25}:5440–5445 (1992).

    Google Scholar 

  47. Z. Gao and A. Eisenberg. A model of micellization for block copolymers in solutions. Macromolecules { vn26}:7353–7360 (1993).

    Google Scholar 

  48. S. Y. Kim, Y. M. Lee, D. J. Baik, and J. S. Kang. Toxic characteristics of methoxy poly(ethyl glycol)/poly(_-caprolactone) nanosphere; in vitro and in vivo studies in the normal mice. Biomaterials { vn24}:55–63 (2003).

    Google Scholar 

  49. R.W.J. Bowers, S.A. Jones, P.W. Stratford, S.A. Charles, Polymeric surface coatings, US Patent 5,648,442 (1994).

  50. E. J. Campbell, V. O'Byrne, P. W. Stratford. Biocompatible surface using methacryloylphosphorylcholine laurylmethacrylate copolymers. ASAIO J. { vn4}0:853–857 (1994).

    Google Scholar 

  51. A. L. Lewis, P. D. Hughes, L. C. Kirkwood, S. W. Leppard, R. P. Redman, L. A. Tolhurst, and P. W. Stratford. Synthesis and characterization of phoshorylchloline-based polymers useful for coating blood filtration devices. Biomaterials { vn21}:1847–1859 (2000).

    Google Scholar 

  52. T. Okano, T. Aoyagi, K. Kataoka, K. Abe, Y. Sakurai, M. Shimada, and I. Shinohara. Hydrophilic-hydrophobic microdomin surfaces having an ability to suppress platelet aggregation and this in vitro antithrombogenicity. J. Biomed. Mater. Res. { vn20}:919–927 (1986).

    Google Scholar 

  53. S. Nagaoka and H. Takiuchi. K Yokota, Y. Mori, H. Tanzawa, T. Kikuchi, Interactions between blood components and hydrogels with poly(oxyethylene) chain of various chain length. Kobunshi Ronbunshu { vn39}:165–171 (1992).

    Google Scholar 

  54. C. D. Tidwell, S. L. Ertel, and B. D. Ratner. Endothelial cell growth and protein adsorption on terminally functionalized, self-assembled monolayers of alkanethiolates on gold. Langmuir { vn13}:3404–3413 (1997).

    Google Scholar 

  55. M. Tanahashi and T. Matsuda. Surface functional-group dependsence on apatite formation on self-assembled monolayers in a simulated body fluid. J. Biomed. Mater. Res. { vn34}:305–315 (1997).

    Google Scholar 

  56. O. Noiset, C. Henneuse, Y.-J. Schneider, and J. Marchand-Brynaert. Surface reactions of poly(aryl ether ether ketone) film: UV spectrophotometric, radiochemical, and X-ray photoelectron spectroscopic assays of hydroxyl functions. Macromolecules { vn30}:540–548 (1997).

    Google Scholar 

  57. T. G. Grasel and S. L. Cooper. Properties and biological interactions of polyurethane anionomers: Effect of sulfonate incorporation. J. Biomed. Mater. Res. { vn23}:311–338 (1989).

    Google Scholar 

  58. Y. H. Kim, D. K. Han, S. Y. Jeong, and K.-D. Ahn. Macromol. Chem. Macromol. Symp. { vn33}:319–326 (1990).

    Google Scholar 

  59. D. K. Han, S. Y. Jeong, Y. H. Kim, B. G. Min, and H. I. Cho. Negative cilia concept for thromboresistance: Synergistic effect of PEO and sulfonate groups grafted onto polyurethanes. J. Biomed. Mater. Res. { vn25}:561–575 (1991).

    Google Scholar 

  60. D. E. Chenoweth. In: E.F. Leonard, V.T. Turitto, and L. Vroman. Blood in Contacts with Natural and Artificial Surfaces, New York Academy of Science, New York, 1987, pp 307–313.

    Google Scholar 

  61. K. Smetana Jr. J. Vacik, M. Houska, D. Souckova, J. Lukas, Macrophage recognition of polymers: effect of carboxylate groups, J. Mater. Sci. Mater. Med. { vn4}:526–529 (1993).

    Google Scholar 

  62. K. Y. Lee, W. S. Ha, and W. H. Park. Blood compatibility and biodegradable of partially N-acylated chitosan derivatives. Biomaterials { vn16}:1211–1216 (1995).

    Google Scholar 

  63. J. S. Lee, M. Kaibara, and H. Sasabe. In vitro rheological evaluation of antithrombogenicity or anticoagulability of styrene derivatives polymer. Biomaterials { vn13}:1025–1030 (1992).

    Google Scholar 

  64. J. A. Hayward and D. Chapman. Biomembrane surface as model for polymer design: the potential for haemocompatibility. Biomaterials { vn5}:135–141 (1985).

    Google Scholar 

  65. D. Chapman. Biocompatible surface based upon the phospholipid asymmetry of biomembranes. Biochem. Soc. Trans. { vn21}:259–263 (1993).

    Google Scholar 

  66. D. Chapman. Biomembranes and new hemocompatible materials. Langmuir { vn9}:39–45 (1993).

    Google Scholar 

  67. K. Ishihara, R. Aragaki, T. Ueda, A. Watenabe, and N. Nakabayashi. Reduced thromobogenicity of polymers having phospholipid polar groups. J. Biomed. Mater. Res. { vn24}:1069–1077 (1990).

    Google Scholar 

  68. M. Kojima, K. Ishihara, A. Watanabe, and N. Nakabayashi. Interaction between phospholipid and biocompatible polymers containing a phosphorylchloline moiety. Biomaterials { vn12}:121–124 (1991).

    Google Scholar 

  69. K. Ishihara, H. Oshida, Y. Endo, T. Ueda, A. Watanabe, and N. Nakabayashi. Hemocompatibility of human whole blood on polymers having phospholipid polar group and its mechanism. J. Biomed. Mater. Res. { vn26}:1543–1552 (1992).

    Google Scholar 

  70. S. F. Zhang, P. Rolfe, G. Wright, W. Lian, A. J. Milling, S. Tanaka, K. Ishihara. Physical and biological properties of compound membranes incorporating a copolymer with a phosphorylchloline head group. Biomaterials { vn19}:691–700 (1998).

    Google Scholar 

  71. N. Morimoto, Y. Iwasaki, N. Nakabayashi, and K. Ishihara. Physical properties and blood compatibility of surface-modified segmented polyurethane by semi-interpenetrating polymer networks with a phospholipid polymer. Biomaterials { vn23}:4881–4887 (2002).

    Google Scholar 

  72. L. Ruiz, D. S. Johnston, S. A. Makobliso, P. Aebischer, and H. J. Mathieu. Biomimetic coatings on silicon wafers: synthesis and characterization. In Mathieu (ed.), Ecasia '95 Proceedings, Chichester, 1996, pp 18–61.

  73. L. Ruiz, J. G. Hilborn, D. Leonard, and H. J. Mathieu. Synthesis, structure and surface dynamics of phosphorylcholine functional biomimicking polymers. Biomaterials { vn19}:987–998 (1998).

    Google Scholar 

  74. K. Ishihara, H. Hanyuda, and N. Nakabayashi. Synthesis of phospholipid polymers having a urethane bond in the side chain as coating material on segmented polyurethane and their platelet adhesion-resistant properties. Biomaterials { vn16}:873–879 (1995).

    Google Scholar 

  75. K. Sugiyama, M. Fukuchi, A. Kishida, M. Akashi, and Y. Kadima. Preparation and characterization of poly(2-methacryloxyethyl phosphorylcholine-co-methyl methacrylete) graft copolyetherurethanes. Kobunshi Ronbunshu { vn53}:48–56 (1996).

    Google Scholar 

  76. K. Ishihara, S. Tanaka, N. Furukawa, K. Kurita, and N. Nakabayashi. Improved blood compatibility of segmented polyurethanes by polymeric additives having phospholipid polar group. I. Molecular design of polymeric additives and their functions. J. Biomed. Mater. { vn32}:391–399 (1996).

    Google Scholar 

  77. K. Ishihara, N. Shibata, and S. Tanaka. Y Iwasaki, T. Kurosaki, and N. Nakabayashi. Improved blood compatibility of segmented polyurethanes by polymeric additives having phospholipid polar group. II. Dispersion state of polymeric additive and protein adsorption on the surface. J. Biomed. Mater. { vn32}:401–408 (1996).

    Google Scholar 

  78. Y. Iwasaki, Y. Aiba, N. Morimoto, N. Nakabayashi, and K. Ishihara. Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane. J. Biomed. Mater. { vn52}:701–708 (2000).

    Google Scholar 

  79. K. Ishihara, H. Nomura, T. Mihara, K. Kurita, Y. Iwasaki, and N. Nakabayashi. Why do phospholipid polymers reduce protein adsorption? J. Biomed. Mater. Res. { vn39}:323–330 (1998).

    Google Scholar 

  80. K. Ishihara, Y. Iwasaki, and C. Nojiri. Phospholipid polymer biomaterials for making ventricular assist devices. J. Conges. Heart Circul. Support { vn1}:265–270 (2001).

    Google Scholar 

  81. T. Yoneyama, K. Ishihara, and N. Nakabayashi. M Ito, Y. Mishima, Short term in vivo evaluation of small-diameter vascular prosthesis composed of segmented poly(etherurethane)/ 2-methacryloxyethyl phosphorylcholine polymer blend. J. Biomed. Mater. Res. { vn43}:15–20 (1998).

    Google Scholar 

  82. L. Dekie, V. Toncheva, P. Dubruel, E. H. Schacht, L. Barrett, and L. W. Seymour. Poly L-glutamic acid derivatives as vectors for gene therapy. J. Control. Rel. { vn65}:187–202 (2000).

    Google Scholar 

  83. P. Ferruti, S. Knobloch, E. Ranucci, E. Gianasi, and R. Duncan. A novel chemical modification of poly-L-lysine reducing toxicity while preserving cationic properties. Proc. Int. Symp. Control. Rel. Bioact. Mater. { vn24}:45–46 (1997).

    Google Scholar 

  84. P. Ferruti, E. Ranucci, L. Sartore, F. Bingnotti, M. A. Marchisio, P. Bianciardi, and F. M. Veronese. Recent results on functional polymers and macromonomers of interests as biomaterials or for biomaterial modification. Biomaterials { vn15}:1235–1241 (1994).

    Google Scholar 

  85. W. Lin, M. C. Garnett, M. C. Davies, F. Bignotti, P. Ferruti, S. S. Davis, and L. Illum. Preparation of surface-modified albumin nanospheres. Biomaterials { vn18}:559–565 (1997).

    Google Scholar 

  86. P. Ferruti, M. A. Marchisio, and R. Barbucci. Synthesis, physicochemical properties and biomedical applications of poly(amidoamine) s. Polymer { vn26}:1336–1348 (1985).

    Google Scholar 

  87. D. Fischer, Y. Li, B. Ahlemeyer, J. Krieglstein, and T. Kissel. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials { vn24}:1121–1131 (2003).

    Google Scholar 

  88. O. Wichterle and D. Lim. Hydrophilic gel in biologic use. Nature { vn185}:117 (1960).

    Google Scholar 

  89. N. A. Pappas. Hydrogels in Medicine and Pharmacy,CRC Press, Boca Raton, FL, 1987.

    Google Scholar 

  90. D. Derossi, K. Kajiwara, Y. Osada, and A. Yamauchi. Polymergels, Fundamentals and Biomedical Applications, Plenum, New York, 1991.

    Google Scholar 

  91. A. S. Hoffman. Hydrogel for biomedical applications. Adv. Drug Del. Rev. { vn54}:3–12 (2002).

  92. T. Miyata, T. Uragami, and K. Nakamae. Biomolecule-sensitive hydrogels. Adv. Drug Del. Rev. { vn54}:79–98 (2002).

    Google Scholar 

  93. K. Smetana Jr., J. Lukas, V. Paleckova, J. Bartunkova, F.-T. Liu, J. Vacik, and H.-J. Gabius. Effect of chemical structure of hydrogels on the adhesion and phenotypic characteristics of human monocytes such as expression of galectins and other carbohydrate-binding sites. Biomaterials { vn18}:1009–1014 (1997).

    Google Scholar 

  94. K. Smetana Jr., J. Vacik, D. Souckova, and J. Sule. The influence of hydrogel functional groups on cell behavior. J. Biomed. Mater. Res. { vn24}:463–470 (1990).

    Google Scholar 

  95. K. Sawada, T. Shimoyama, P. S. Malchesky, J. B. Goldcamp, and S. Omokawa. Evaluation of a relationship between polymer bulk hydroxyl and surface oxygen content and in vitro serummaterial interaction. J. Biomed. Mater. Res. { vn27}:547–555 (1993).

    Google Scholar 

  96. K. Sawada, P. S. Malchesky, J. M. Guidubaldi, A. Sueoka, T., Shimoyama. In vitro evaluation of relationship between human serum-or plasma-material interaction and. polymer bulk hydroxyl and surface oxygen content. ASAIO J. { vn39}:910–917 (1993).

    Google Scholar 

  97. N. Ashammakhi and P. Rokkanen. Absorbable polyglycolide device in trauma and bone surgery. Biomaterials { vn18}:3–9 (1997).

    Google Scholar 

  98. N. Kumar, R. S. Langer, and A. J. Domb. Polyanhydrides: an overview. Adv. Drug Del. Rev. { vn54}:889–910 (2002).

    Google Scholar 

  99. B. Burnham. Polymers for delivering peptides and proteins. Am. J. Hosp. Pharm. { vn51}:210–218 (1994).

    Google Scholar 

  100. Y. Tsutsumi, T. Kihira, S.-I. Tsunoda, N. Okada, Y. Kaneda, Y. Ohsugi, M. Nakagawa, and T. Mayumi. Polyethelene glycol modification of interleukin-6 enhances its thrombopoietic activity. J. Control. Rel. { vn33}:447–451 (1995).

    Google Scholar 

  101. R. Cref, Y. Minamitake, M. T. Peracchia, V. Trubetskoy, V. Torchilin, and R. Langer. Biodegradable long circulating polymer nanospheres. Science { vn263}:1600–1603 (1994).

    Google Scholar 

  102. R. Cref, A. Domb, P. Quellec, T. Blunk, R. H. Muller, J. M. Verbavatz, and R. Langer. The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv. Drug Del. Rev. { vn16}:215–233 (1995).

    Google Scholar 

  103. C. Scholz, M. Iijima, Y. Nagasaki, and K. Kataoka. A novel reactive polymeric micelles with aldehyde groups on its surface. Macromolecules { vn28}:7295–7297 (1995).

    Google Scholar 

  104. X. Chang and H. M. Burt. Diblock copolymers of poly(DLlactide)-block-methoxy poly(ethylene glycol) as micellar carrier of Taxol. Pharm. Res. { vn12}:S265-269 (1995).

    Google Scholar 

  105. K. M. Yamada. Adhesive recognition sequences. J. Biol. Chem. { vn266}:12809–12812 (1991).

    Google Scholar 

  106. R. Pasqualini and E. Ruosiahti. Organ targeting in vivo using phage display peptide libraries. Nature { vn380}:364–366 (1996).

    Google Scholar 

  107. D. J. Irvine, A. M. Mayes, and L. G. Griffith. Nanoscale clustering of RGD peptides at surfaces using comb polymers. 1. Synthesis and characterization of comb thin films. Biomacromolecules { vn2}:85–94 (2001).

    Google Scholar 

  108. D. J. Irvine, A.-V. G. Ruzette, A. M. Mayes, and L. G. Griffith. Nanoscale clustering of RGD peptides at surfaces using comb polymers. 2. Surface segregation of comb polymers in polylactide. Biomacromolecules { vn2}:545–556 (2001).

    Google Scholar 

  109. P. Banerjee, D. J. Irvine, A. M. Mayes, and L. G. Griffith. Polymer latexes for cell-resistant and cell-interactive surfaces. J. Biomed. Mater. Res. { vn5}0:331–339 (2000).

    Google Scholar 

  110. L. Y. Koo, D. J. Irvine, A. M. Mayes, D. A. Lauffenburger, and L. G. Griffith. Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus. J. Cell Sci. { vn115}:1423–1433 (2002).

    Google Scholar 

  111. C. Roberts, C. S. Chen, M. Mrksich, V. Martichonok, D. E. Ingber, and G. M. Whitesides. Using mixed self-assembled monolayers presenting RGD and (EG)3OH groups to characterize long-term attachment of bovine capillary endothelial cells to surface. J. Am. Chem. Soc. { vn120}:6548–6555 (1998).

    Google Scholar 

  112. S. M. Cannizzaro, R. F. Padera, R. Langer, R. A. Rogers, F. E. Black, M. C. Davies, S. J. B. Tendler, and K. M. Shakesheff. A novel biotinylated degradable polymer for cell-interactive application. Biotechnol. Bioeng. { vn58}:529–535 (1998).

    Google Scholar 

  113. E. J. Gordon, W. J. Sanders, and L. L. Kiessling. Synthetic ligands point to cell surface strategies. Nature { vn392}:30–31 (1998).

    Google Scholar 

  114. L. J. Strausbaugh. Intracarotid infusions of protamine sulfate disrupts the blood-brain barrier of rabbits. Brain Res. { vn409}:221–226 (1987).

    Google Scholar 

  115. J. C. Horrow. Protamine: a review of its toxicity. Anesth. Analog. { vn64}:221–226 (1985).

    Google Scholar 

  116. I. Westrgren and B. B. Jhansson. Altering the blood-brain barrier in the rat by intracarotid infusion of polycations: a comparison between potamine, poly-L-lysine and poly-L-arginine. Acta Physiol. Scand. { vn149}:99–104 (1993).

    Google Scholar 

  117. J. A. Broestle and S. N. Emancipator. Rat mesangial cell lysis in vitro is induced by cationic polypeptides. Am. J. Pathol. { vn142}: 529–539 (1993).

    Google Scholar 

  118. S. Choksakulnimitr, S. Masuda, H. Tokuda, Y. Takakura, and M. Hashida. In vitro cytotoxicity of macromolecules in different cell culture systems. J. Control. Rel. { vn34}:233–241 (1995).

    Google Scholar 

  119. F. Maillet, D. Labarre, and M. D. Kazatchkine. The role of naturally-occurring antibodies against man-made materials in biocompatibility. Transfus. Sci. { vn11}:33–41 (1990).

    Google Scholar 

  120. B. Rihova. Biocompatibility of biomaterials: hemocompatibility, immunocompatibility and biocompatibility of solid polymeric materials and soluble polymeric carriers. Adv. Drug Del. Rev. { vn21}:157–176 (1996).

    Google Scholar 

  121. P. J. Baker, T. F. Lint, B. C. Mcleod, C. C. Behrends, and J. Gewurz. Studies on the inhibition of C56-induced lysis (reactive lysis). VI. Modulation of C56-induced lysis by polyanions and polycations. J. Immunol. { vn114}:554–558 (1976).

    Google Scholar 

  122. M. Loos, J. E. Volanakis, and R. M. Stroud. Mode of interaction of different polyanions with the first (C1, C1), the second (C2) and the forth (C4) component of complement-III, Inhibition of C4 and C2 binding site(s) on C1s by polyanions. Immunochemistry { vn13}:789–791 (1976).

    Google Scholar 

  123. E. Raepple, H. U. Hill, and M. Loos. Mode of interaction of different polyanions with the first (C1, C1), the second (C2) and the forth (C4) component of complement-1. Effect of fluid phase C1 and on C1 bound to EA or to EAC4. Immunochemistry { vn13}:251–255 (1976).

    Google Scholar 

  124. G. W. Webster and W. P. McArther. Inhibition of the classical and alternative pathway of human and guinea pig complement by pyran copolymer. Int. Arch. Allergy { vn66}:304–309 (1981).

    Google Scholar 

  125. W. G. Brodbeck, M. S. Shive, E. Colton, Y. Nakayama, T. Matsuda, and J. M. Anderson. Influence of biomaterial surface chemistry on the apoptosis of adherent cells. J. Biomed. Mater. Res. { vn55}:661–668 (2001).

    Google Scholar 

  126. Y. Takakura, T. Fujita, H. Furitsu, M. Nishikawa, H. Sezaki, and M. Hashida. Pharmacokinetics of succinylated proteins and dextran sulfate in mice: implications for hepatic targeting of protein drugs by direct succinylation via seavenger receptors. Int. J. Pharm. { vn105}:19–29 (1994).

    Google Scholar 

  127. N. Hamamoto, Y. Hamamoto, T. Nakajima, and H. Ozawa. Histological, histocytochemical and ultrastructural study on the effects of surface charge on bone formation in the rabbit mandible. Arch. Oral Biol. { vn4}0:97–106 (1995).

    Google Scholar 

  128. M. Krukowski, R. A. Shively, P. Osdoby, and B. L. Eppley. Stimulation of craniofacial and intramedullary bone formation by negatively charged beads. J. Oral Maxillofac. Surg. { vn48}:468–475 (1990).

    Google Scholar 

  129. D. M. Morgan, J. Clover, and J. D. Pearson. Effects of synthetic polycations on leucine incorporation, lactate dehydrogenase release, and morphology of human unbilical vein endothelial call. J. Cell Sci. { vn91}:231–238 (1988).

    Google Scholar 

  130. D. M. Morgan, V. L. Larvin, and J. L. Pearson. Biochemical characterization of polycation-induced cytotoxicity to human vascular endothelial cells. J. Cell Sci. { vn94}:553–559 (1989).

    Google Scholar 

  131. J. Haensler and F. C. Szoka. Polyamidoamine cascade polymer mediate efficient transfection of cell in culture. Bioconj. Chem. { vn4}:372–379 (1993).

    Google Scholar 

  132. D. Fischer, T. Bieber, H. P. Elsasser, and T. Kissel. Polyethylenimine: synthesis and in vitro cytotoxicity of low molecular weight polycation for gene transfer. Eur. J. Cell Biol. { vn75}:108–112 (1998).

    Google Scholar 

  133. D. Fischer, T. Bieber, Y. Li, H.-P. Elsasser, and T. Kissel. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res. { vn16}:1273–1279 (1999).

    Google Scholar 

  134. H. J. P. Ryser. A membrane effect of basic polymers dependent on molecular size. Nature { vn215}:45–46 (1967).

    Google Scholar 

  135. A. K. Singh, B. S. Kasinath, and E. J. Lewis. Interaction of polycations with cell-surface negative charges of epithelial cells. Biochim. Biophys. Acta { vn1120}:337–342 (1992).

    Google Scholar 

  136. D. M. Brunnette. The effect of implant surface topography on the behavior of cell. Int. J. Oral Maxillofac. Implants { vn3}:231–246 (1988).

    Google Scholar 

  137. D. M. Brunnette. The effect of surface topography on cell migration and adhesion. In R.D. Ratner (ed.), Surface Characterization of Biomaterials, Elsevier, Amsterdam, 1988, pp. 203–217.

    Google Scholar 

  138. C.E. Campbell and A.F. von Recum. Micro-topography and soft tissue response. J. Invest. Surg. { vn2}:51–74 (1989).

    Google Scholar 

  139. J. A. Schmidt and A. F. von Recum. Texturing of polymer surfaces at the cellular level. Biomaterials { vn12}:385–389 (1991).

    Google Scholar 

  140. J. I. Sheppard, W. G. McClung, and I. A. Feuerstein. Adherent platelet morphology on absorbed fibrinogen: effects of protein incubation time and albumin addition. J. Biomed. Mater. Res. { vn28}:1175–1186 (1994).

    Google Scholar 

  141. J. S. Burmeister, J. D. Vrany, W. M. Reidhert, and G. A. Truskey. Effect of fibronectin amount and conformation on the strength of endothelial cell adhesion to HEMA/EMA copolymers. J. Biomed. Mater. Res. { vn30}:13–22 (1996).

    Google Scholar 

  142. M. Lampin, R. Warocquier-Clerout, C. Legris, M. Degrange, and M. F. Sigot-Luizard. Correlation between substratum roughness and wettability, cell adhesion, and cell migration. J. Biomed. Mater. Res. { vn36}:99–108 (1997).

    Google Scholar 

  143. A. Curtis and C. Wilkinson. Topographical control of cells. Biomaterials { vn18}:1573–1583 (1997).

    Google Scholar 

  144. C. S. Ranucci and P. V. Moghe. Substrate microtopography can enhance cell adhesive and migratory responsiveness to matrix ligand density. J. Biomed. Mater. Res. { vn54}:149–161 (2001).

    Google Scholar 

  145. B. Kasemo. Biological surface science. Surface Science { vn500}:656–677 (2002).

    Google Scholar 

  146. D. Qin, Y. Xia, J. A. Rogers, R. J. Jackman, X.-M. Zhao, and G. M. Whitesides. Microfabrication, microstructures and microsystems. In A. Manz and H. Becker (eds.), Microsystem Technology in Chemistry and Life Science, Springer-Verlag, Berlin, 1998, pp. 1–20.

    Google Scholar 

  147. R. S. Kane, S. Takayama, E. Ostuni, D. E. Ingber, and G. M. Whitesides. Patterning proteins and cells using soft lithography. Biomaterials { vn20}:2363–2376 (1999).

    Google Scholar 

  148. S. Zhang, L. Yan, M. Altman, M. Lassle, H. Nugent, F. Frankel, D. A. Lauffenburger, G. M. Whietsides, and A. Rich. Biological surface engineering: a simple system for cell pattern formation. Biomaterials { vn20}:1213–1220 (1999).

    Google Scholar 

  149. R. C. Chapman, E. Ostuni, L. Yan, and G. M. Whitesides. Preparation of mixed self-assembled monolayers (SAMs) that resist adsorption of proteins using the reaction of amines with a SAM that present interchain carboxylic anhydride groups. Langmuir { vn16}:6927–6936 (2000).

    Google Scholar 

  150. P. Korbelar, J. Vacik, and I. Dylevsky. Experimental implantation of hydrogel into the bone. J. Biomed. Mater. Res. { vn22}:751–762 (1988).

    Google Scholar 

  151. P. J. VandeVord, H. W. T. Matthew, S. P. DeSilva, L. Mayton, B. Wu, and P. H. Wooley. Evaluation of the biocompatibility of a chitosan scaffold in mice. J. Biomed. Mater. Res. { vn59}:585–590 (2002).

    Google Scholar 

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Authors and Affiliations

  1. Fiber & Electro-Optics Research Center, Virginia Tech, Blacksburg, Virginia, 24061, USA

    You-Xiong Wang & Richard O. Claus

  2. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia, 24061, USA

    John L. Robertson

  3. Virginia Tech Applied Biosciences Center, Virginia Tech, Blacksburg, Virginia, 24061, USA

    William B. Spillman Jr.

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Wang, YX., Robertson, J.L., Spillman, W.B. et al. Effects of the Chemical Structure and the Surface Properties of Polymeric Biomaterials on Their Biocompatibility. Pharm Res 21, 1362–1373 (2004). https://doi.org/10.1023/B:PHAM.0000036909.41843.18

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