Loading of collagen-heparan sulfate matrices with bFGF promotes angiogenesis and tissue generation in rats

Authors

  • J. S. Pieper,

    1. Department of Biochemistry, 194, University Medical Center Nijmegen, NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
    Search for more papers by this author
  • T. Hafmans,

    1. Department of Biochemistry, 194, University Medical Center Nijmegen, NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
    Search for more papers by this author
  • P. B. van Wachem,

    1. Department of Pathology Laboratory, Medical Biology and Tissue Engineering, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
    Search for more papers by this author
  • M. J. A. van Luyn,

    1. Department of Pathology Laboratory, Medical Biology and Tissue Engineering, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
    Search for more papers by this author
  • L. A. Brouwer,

    1. Department of Pathology Laboratory, Medical Biology and Tissue Engineering, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
    Search for more papers by this author
  • J. H. Veerkamp,

    1. Department of Biochemistry, 194, University Medical Center Nijmegen, NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
    Search for more papers by this author
  • T. H. van Kuppevelt

    Corresponding author
    1. Department of Biochemistry, 194, University Medical Center Nijmegen, NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
    • Department of Biochemistry, 194, University Medical Center Nijmegen, NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
    Search for more papers by this author

Abstract

The loading of biocompatible matrices with growth factors offers the opportunity to induce specific cell behavior. The attachment of heparan sulfate (HS) to these matrices may promote the binding, modulation, and sustained release of signaling molecules. In this study, basic fibroblast growth factor (bFGF) was bound to crosslinked collagenous matrices with and without covalently attached HS. The tissue response to these matrices was evaluated after subcutaneous implantation in rats. Attachment of HS to collagen matrices increased the bFGF binding capacity threefold and resulted in a more gradual and sustained release of the growth factor in vitro. bFGF primarily was located at the matrix margins. In vivo, the presence of HS without bFGF resulted in a transient vascularization, predominantly at the matrix periphery. Angiogenesis was further enhanced by combining HS with bFGF. In contrast to collagen-HS and collagen/bFGF matrices, collagen-HS/bFGF matrices remained highly vascularized throughout the matrix during the 10-week implantation period. In addition, these latter matrices revealed an intense and prolonged tissue response and considerably promoted the generation of new tissue. Foreign body reactions were only observed sporadically at this time interval. It is concluded that bFGF loading of collagen-HS matrices has additional value for those tissue-engineering applications that require enhanced angiogenesis and generation of new tissue. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 185–194, 2002

Ancillary