title: 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.
authors.affiliation: School of Chemical, Biological and Materials Engineering, University of Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK 73019, USA.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Alvarez-Barreto
authors.forename: Bonnie
authors.initials: B
authors.lastname: Landy
authors.forename: Samuel
authors.initials: S
authors.lastname: VanGordon
authors.forename: Laura
authors.initials: L
authors.lastname: Place
authors.forename: Paul L
authors.initials: PL
authors.lastname: DeAngelis
authors.forename: Vassilios I
authors.initials: VI
authors.lastname: Sikavitsas
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects*; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008859:Microscopy, Polarization; D008903:Minerals / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D008903:Minerals; D009842:Oligopeptides; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C047981:arginyl-glycyl-aspartic acid; D000469:Alkaline Phosphatase