Enhanced osteoblastic differentiation of mesenchymal stem cells seeded in RGD-functionalized PLLA scaffolds and cultured in a flow perfusion bioreactor

Abstract

The present study combines chemical and mechanical stimuli to modulate the osteogenic differentiation of mesenchymal stem cells (MSCs). Arg-Gly-Asp (RGD) peptides incorporated into biomaterials have been shown to upregulate MSC osteoblastic differentiation. However, these effects have been assessed under static culture conditions, while it has been reported that flow perfusion also has an enhancing effect on MSC osteoblastic differentiation. It is clear that there is a need to combine RGD modification of biomaterials with mechanical stimulation of MSCs via flow perfusion and evaluate its effects on MSC differentiation down the osteogenic lineage. In this study, the effect of different levels of RGD modification of poly(L-lactic acid) scaffolds on MSC osteogenesis was evaluated under conditions of flow perfusion. It was found that there is a synergistic enhancement of different osteogenic markers, due to the combination of flow perfusion and RGD surface modification when compared to their individual effects. Furthermore, under conditions of flow perfusion, there is an RGD surface concentration optimal for differentiation, and it is flow rate-dependent. This report underlines the significance of incorporating combined biomimesis via biochemical and mechanical microenvironments that modulate in vivo cell behaviour and tissue function for more efficient tissue-engineering strategies.

Using polymeric materials to control stem cell behavior for tissue regeneration

“…Common techniques of surface functionalization include chemical modifications via cross-linking polymer chains with bioactive factors, physical modifications via physisorption of the molecules onto the surface, or physical entrapment (Alvarez-Barreto et al, 2011). …”

“…The positive role of RGD in cell adhesion has been widely demonstrated with various materials, including glasses, hydroxyapatite and polymers (Alvarez-Barreto et al, 2011; De Giglio et al, 2000; Morgan et al, 2008). Support of osteogenic differentiation by the presence of RGD is also dose-dependent (Meinel et al 2004, Shin et al 2005 in Alvarez-Barreto et al 2011).…”

“…The positive role of RGD in cell adhesion has been widely demonstrated with various materials, including glasses, hydroxyapatite and polymers (Alvarez-Barreto et al, 2011; De Giglio et al, 2000; Morgan et al, 2008). Support of osteogenic differentiation by the presence of RGD is also dose-dependent (Meinel et al 2004, Shin et al 2005 in Alvarez-Barreto et al 2011). Other peptides and ligands such as the collagen-mimetic peptide, GFOGER can accelerate and increase bone formation, and improve osseointegration of bone into an implant in vivo (Petrie et al, 2008; Phillips et al, 2008; Reyes et al, 2007; Wojtowicz et al, 2010).…”

“…Compared to natural polymers, synthetic polymers can be more easily synthesized on a large scale with more precisely controlled molecular weight and addition of functional groups. However, synthetic polymers in their native state can only support cell adhesion and growth to a limited extent since they lack functional groups for cell interaction (Alvarez-Barreto et al, 2011). The synthetic polymers that have received the most study are poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) (PEG), polycaprolactones, polyorthoesters, polyanhydrides and polycarbonates (Chan and Mooney, 2008).…”

A Comprehensive Review on the Role of Various Materials in the Osteogenic Differentiation of Mesenchymal Stem Cells with a Special Focus on the Association of Heat Shock Proteins and Nanoparticles

“…George et al [2006] demonstrated that the honeycomb collagen sponge is an excellent scaffold for MSC proliferation and osteogenic differentiation. In another study, it was shown that the incorporation of Arg-Gly-Asp (RGD)-functionalized peptides in PLLA scaffolds upregulates osteoblastic differentiation [Alvarez-Barreto et al, 2011]. A study on electrospun poly-epsilon-caprolactone PCL fiber mesh scaffolds with or without the decellularized ECM construct (PCL/ECM) dexamethasone was performed [Thibault et al, 2010].…”