Heparin-functionalized hydrogels as growth factor-signaling substrates

Abstract

Tuneable, bioactive hydrogels present an attractive option as cell-instructive substrates for tissue regeneration. Properties mimicking the extracellular matrix at the site of injury are sought after, in particular the ability to regulate growth factors that are key to the regeneration process. This study demonstrates the successful formation of hydrogels with heparin functionalities and fibroblast growth factor-2 (FGF-2). Poly(2-hydroxyethyl methacrylate)-heparin hydrogels were capable of retaining FGF-2 by specific binding to heparin and subsequently showed sustained presentation of the growth factor to mesenchymal stromal cells (MSC). Heparin acted as stable anchoring molecules for FGF-2 on the substrate and the synergistic effect of the ensuing heparin-FGF-2 complex was evident in supporting long term cell growth. The presence of heparin during 3D scaffold formation was also found to introduce surface roughness and microporosity to the resulting hydrogels. While FGF-2 has been known to encourage MSC growth and maintain their multilineage potential, other heparin-binding ligands such as bone morphogenetic proteins are potent differentiation stimuli for MSC. Therefore preserving MSC multipotency or a push toward a differentiation pathway may be pursued by the choice of ligand applied to and bound by the heparin functionalities on the current substrate.

Keywords: fibroblast growth factors; heparin; hydrogels; mesenchymal stromal cells; tissue scaffolds.