Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell organization

Phil G. Campbell, Eric D. Miller, Gregory W. Fisher, Lynn M. Walker, Lee E. Weiss

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

The purpose of this study was to initiate the exploration of cell behavioral responses to inkjet printed spatial patterns of hormones biologically immobilized on biomimetic substrates. This approach was investigated using the example of preosteoblastic cell response in vitro to fibroblast growth factor-2 (FGF-2) printed on fibrin films. Concentration modulated patterns of FGF-2, including continuous concentration gradients, were created by overprinting dilute FGF-2 bioinks with a custom inkjet printer. The immobilized FGF-2 was biologically active and the printed patterns persisted up to 10 days under cell culture conditions. Cell numbers increased in register to printed patterns from an initial random uniform cell distribution across the patterned and non-patterned fibrin substrate. Patterned immobilized FGF-2, not cell attachment directed cell organization because the fibrin substrate was homogeneous. The capability to engineer arbitrary and persistent hormone patterns is relevant to basic studies across various fields including developmental biology and tissue regeneration. Furthermore, since this hormone inkjet printing methodology is extensible to create complex three-dimensional structures, this methodology has potential to create therapies for tissue engineering using spatial patterned delivery of exogenous hormones.

Original languageEnglish (US)
Pages (from-to)6762-6770
Number of pages9
JournalBiomaterials
Volume26
Issue number33
DOIs
StatePublished - Nov 2005
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported partially by the Office of Naval Research (Grant No. N000140110766), the National Science Foundation (Grants No. CTS-0210238 and DMI-9800565), the National Institutes of Health (Grant No. 1 R01 EB00 364-01), the Pennsylvania Infrastructure Technology Alliance (PITA) from the Pennsylvania Department of Community and Economic Development, the Health Resources and Services Administration (Grant No. 1C76 HF 00381-01), the Scaife Foundation, and the Philip and Marsha Dowd Engineering Seed Fund. We wish to thank Aventis Behring, L.L.C. (King of Prussia, PA) for their generous gift of lyophilized human fibrinogen and thrombin, and PROCHON (Rehovot, Israel) for biotinylated FGF-2. The authors declare that they have no competing financial interests.

Keywords

  • Biological patterning
  • Growth factor
  • Inkjet technology
  • Printing technology
  • Solid freeform fabrication
  • Tissue engineering

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