Modeling early stage bone regeneration with biomimetic electrospun fibrinogen nanofibers and adipose-derived mesenchymal stem cells

Abstract

The key events of the earliest stages of bone regeneration have been described in vivo although not yet modeled in an in vitro environment, where mechanistic cell-matrix-growth factor interactions can be more effectively studied. Here, we explore an early-stage bone regeneration model where the ability of electrospun fibrinogen (Fg) nanofibers to regulate osteoblastogenesis between distinct mesenchymal stem cells populations is assessed. Electrospun scaffolds of Fg, polydioxanone (PDO), and a Fg:PDO blend were seeded with adipose-derived mesenchymal stem cells (ASCs) and grown for 7-21 days in osteogenic differentiation media or control growth media. Scaffolds were analyzed weekly for histologic and molecular evidence of osteoblastogenesis. In response to osteogenic differentiation media, ASCs seeded on the Fg scaffolds exhibit elevated expression of multiple genes associated with osteoblastogenesis. Histologic stains and scanning electron microscopy demonstrate widespread mineralization within the scaffolds, as well as de novo type I collagen synthesis. Our data demonstrates that electrospun Fg nanofibers support ASC osteogenic differentiation, yet the scaffold itself does not appear to be osteoinductive. Together, ASCs and Fg recapitulate early stages of bone regeneration ex vivo and presents a prospective autologous therapeutic approach for bone repair.