Induction of Myogenic Differentiation of Human Mesenchymal Stem Cells Cultured on Notch Agonist (Jagged-1) Modified Biodegradable Scaffold Surface

Abstract

Engineered scaffold surface provides stem cells with vital cues that could determine the eventual fate of stem cells. In this work, biodegradable poly­(l-lactide-<i>co</i>-ε-caprolactone) (PLCL) scaffold conjugated with Notch agonist-Jagged-1­(JAG) peptide (2.1 kDa) was prepared to initiate myogenic differentiation of human mesenchymal stem cells (hMSCs). The scaffold surface was activated with oxygen plasma and acrylic acid was engrafted via UV polymerization to form a surface bearing carboxylic groups. JAG peptide was subsequently immobilized onto the carboxylated scaffold surface. Surface chemistry and topography were examined using attenuated total reflection Fourier transform infrared, X-ray photoelectron spectroscopy, and atomic force microscopy. Quantitative real time polymerase chain reaction analysis revealed activation of the Notch pathway; furthermore, several specific markers associated with myogenic but not osteogenic differentiation were shown to be up-regulated in hMSCs cultured on the engineered surface. The pro-myocardial effect of surface bound JAG peptide was further affirmed via immunodetection of the distinct myocardial marker, cardiac troponin T. Collectively, our results suggest that PLCL conjugated JAG peptide is a viable strategy to enhance the functional potential of scaffolds to be used as a bioengineered cardiac patch in myocardial infarction repair

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