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

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.