Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo

Abstract

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro and can recapitulate certain ECM functions that support cell growth and differentiation. However, ECM-derived matrices suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed synthetic matrices that can also recapitulate ECM roles. Synthetic matrices have certain limitations as they use synthetic peptides or fragments whereas the ECM consists of full proteins. Here, we report the development of degradable, PEG-based hydrogels of controlled stiffness that incorporate full-length fibronectin (FN) to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), in these hydrogels to enhance angiogenesis and bone regeneration, respectively. We show that the solid-state presentation of growth factors enables very low growth factor doses to achieve regenerative effects.