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Controlled Release of Fibroblast Growth Factor: Activity in Cell Culture

Published online by Cambridge University Press:  15 February 2011

Matthew A. Nugent ,
Oliver S. Chen  and
Elazer R. Edelman
Matthew A. Nugent
Affiliation:
Harvard-M.I.T., Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
Oliver S. Chen
Affiliation:
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
Elazer R. Edelman
Affiliation:
Harvard-M.I.T., Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 Cardiovascular Division, Department of Internal Medicine, Brigham and Woman's Hospital and Harvard Medical School, Boston, MA 02115
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Abstract

Basic fibroblast growth factor is a multi-potent cell regulatory factor that stimulates proliferation and angiogenesis. Controlled studies of basic fibroblast growth factor in animals have been hindered by the instability of this protein. In addition, many cells appear to require the continuous addition of basic fibroblast growth factor for optimal growth and function in culture. A system for the sustained delivery of active basic fibroblast growth factor might provide both a means to conduct log-term studies on activity and provide a practical alternative to multiple growth factor additions to cell cultures. Basic fibroblast growth factor was incorporated into standard polymer matrices, but the released growth factor had lost over 99% of its bioactivity. Loss of basic fibroblast growth factor activity was found to result from both physical inactivation and adsorption of the protein to surfaces. These problems were avoided by incorporating the growth factor into calcium cross-linked alginate microspheres containing heparinsepharose beads. Basic fibroblast growth factor was incorporated into these microspheres with 71% efficiency and active growth factor was released with predictable kinetics for up to 7 weeks. Release from these microspheres was controlled by the amount of heparin within the device and could be manipulated by simply altering the heparin content during fabrication. Alginate/heparin-sepharose microspheres were placed into growing cultures of bovine aortic endothelial cells and no cytotoxic effects were observed. Furthermore, microspheres containing growth factor provided long-term stimulation of cell proliferation and maintenance of endothelial cell morphology.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 252: Symposium T – Tissue-Inducing Biomaterials , 1991 , 273
Copyright
Copyright © Materials Research Society 1992

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References

REFERENCES

1. Sporn, M. B. and Roberts, A. B., in Peptide Growth Factors and Their Receptors I, edited by Sporn, M.B. and Roberts, A.B. (Springer-Verlag, Berlin Heidelberg, 1990), pp 3–15.Google Scholar
2. Murray, J., Brown, L., Klagsbrun, M., and Langer, R., In Vitro 19, 743–748 (1983).CrossRefGoogle Scholar
3. Silberstein, G.B. and Daniel, C.W., Science 237, 291–293 (1987).CrossRefGoogle Scholar
4. Burgess, W.H. and Maciag, T., Annu. Rev. Biochem. 58. 575–606 (1989).Google Scholar
5. Klagsbrun, M., Prog. Growth Factor Res. 1, 207–235 (1989).Google Scholar
6. Rifkin, D.B. and Moscatelli, D., J. Cell Biol. 109, 1–6 (1989).CrossRefGoogle Scholar
7. Whalen, G.F., Shing, Y. and Folkman, J., Growth Factors, 1, 157–164 (1989).CrossRefGoogle Scholar
8. Hayek, A., Culler, F.L., Beattie, G.M., Lopez, A.D., Cuevas, P. and Baird, A., Biochem. Biophys. Res. Comm. 147, 876–880 (1987).Google Scholar
9. Thompson, J.A., Anderson, K.D., DiPietro, J.M., Zwiebel, J.A., Zametta, M., Anderson, W.F., Science 241, 1349–1352 (1988).CrossRefGoogle Scholar
10. Bashkin, P., Doctrow, S., Klagsbrun, M., Svahn, C.M., Folkman, J., and Vlodavsky, I., Biochem. 28, 1737–1743 (1989).Google Scholar
11. Rhine, W., Hsieh, D. and Langer, R., J. Pharm. Sci. 69, 265–270 (1980).CrossRefGoogle Scholar
12. Edelman, E.R., Mathiowitz, E., Langer, R. and Klagsbrun, M., Biomaterials 12, 619–626 (1991).Google Scholar
13. Gospodarowicz, D. and Cheng, J., J. Cell Physiol. 128, 475–484 (1986).Google Scholar
14. Tanaka, H., Matsumura, M. and Veliky, I.A., Biotechnol. Bioeng. 26, 53–58 (1984).Google Scholar
15. Smidsrød, O. and Skjåk-Bræk, G., Trends Biotechnol. 8, 74–81 (1990).Google Scholar
16. Edelman, E.R., Nugent, M.A., Smith, L.T. and Karnovsky, M.J., J. Clin. Invest. (in press).Google Scholar