Integration of Nanoscale and Macroscale cues in Bone Regeneration

Abstract

Marrow stromal cells (MSC) can act as a pluripotent source of reparative cells during injury. Many envisioned applications of MSC, such as treating large defects in bone, involve in vivo implantation of MSC attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to MSC survival and proliferation ‐ especially in large defects. We address ways of integrating nanoscale control of growth factor presentation with macroscale design of scaffold architecture with an eye toward influencing multiple biological processes, including growth, proliferation, migration, and differentiation of cells that contribute to bone formation. We have focused especially on the role of epidermal growth factor (EGF) receptor signalling. For some cell types, soluble EGF acts as a survival signal in the face of pro‐death stimuli, but MSC appear refractory toward survival when challenged with pro‐death stimuli in the presence of soluble EGF. In contrast, when EGF is covalently tethered to the scaffold, it can activate the EGFR signaling pathways and strongly promotes spreading and survival of MSC. Substrate‐tethered EGF also influences proliferation, colony formation, and differentiation of human MSC, hence holds potential for enhancing bone regeneration.