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

Sara Trujllo, Cristina González-García, Patricia Rico, Andrew Reid, James Windmill, Matthew J. Dalby, Manuel Salmerón-Sánchez

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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.
Original languageEnglish
Article number120104
Number of pages15
JournalBiomaterials
Volume252
Early online date7 May 2020
DOIs
Publication statusE-pub ahead of print - 7 May 2020

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Keywords

  • hydrogels
  • growth factors
  • fibronectin
  • poly(ethylene) glycol
  • bone
  • vascularization

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