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

Abstract

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.

Poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/fibrinogen/bredigite nanofibrous membranes and their integration with osteoblasts for guided bone regeneration

“…The results of mechanical strength test demonstrated that Young's modulus and tensile strength of PHBV nanofibrous membranes got decreased upon blending with fibrinogen. Although fibrinogen is a highly bioactive biomaterial but shows limited mechanical integrity compared to synthetic polymers . Incorporation of BR nanoparticles within the nanofibers resulted in a significant increase in Young's modulus and tensile strength of PHBV/FG/BR compared to PHBV/FG and PHBV membranes.…”

“…Although fibrinogen is a highly bioactive biomaterial but shows limited mechanical integrity compared to synthetic polymers. 16,[35][36][37] Incorporation of BR nanoparticles within the nanofibers resulted in a significant increase in Young's modulus and tensile strength of PHBV/FG/BR compared to PHBV/FG and PHBV membranes. In our previous study, it was demonstrated that the addition of BR nanoparticles into PHBV nanofibers up to 10% resulted in improved tensile strength and increased resistance to deformation of PHBV membranes because of the reinforcement effect of BR nanoparticles within the polymer matrix.…”

Pneumatospinning of collagen microfibers from benign solvents

“…Electrospinning is a well-established bottom-up fiber production method dating back to at least 1900 [1]. Electrospinning of polymers from liquid solutions is a technique that has been used widely in the generation of three-dimensional (3D) fibrous scaffolds for tissue engineering applications [2][3][4][5][6][7][8]. This technology allows formation of fibers with diameters ranging from tens of nanometers to several microns.…”

Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering

“…Due to their unique features, the use of nanofibrous electrospun scaffolds in tissue engineering is expanding rapidly. Polycaprolactone/collagen/hydroxyapatite (PCL/col./HA) [60], fibrinogen/polydioxanone (Fg/PDO) [61], and polycaprolactone/polylactic acid (PCL/ PLA) [62] nanofibrous electrospun scaffolds have been shown to promote bone regeneration in vitro when seeded with human MSCs. In diabetic animal models, 3D poly(lactic acid-coglycolic acid) (PLGA) electrospun scaffolds have been used for chronic wound repair [63], while poly-L-lactide acid (PLLA) electrospun devices have been able to improve insulin Fig.…”