Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors

Abstract

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length 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. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.

Keywords: Bone; Fibronectin; Growth factors; Hydrogels; Vascularisation; poly(ethylene) glycol.