Peptide-Functionalized Nanostructured Microarchitectures Enable Rapid Mechanotransductive Differentiation

Zongjie Wang; Libing Zhang; Mahmoud Labib; Haijie Chen; Mingyang Wei; Mahla Poudineh; Brenda J. Green; Bill Duong; Jagotamoy Das; Sharif Ahmed; Edward H. Sargent; Shana O. Kelley

doi:10.1021/acsami.9b13694

Peptide-Functionalized Nanostructured Microarchitectures Enable Rapid Mechanotransductive Differentiation

Zongjie Wang, Libing Zhang, Mahmoud Labib, Haijie Chen, Mingyang Wei, Mahla Poudineh, Brenda J. Green, Bill Duong, Jagotamoy Das, Sharif Ahmed, Edward H. Sargent, Shana O. Kelley^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Microenvironmental factors play critical roles in regulating stem cell fate, providing a rationale to engineer biomimetic microenvironments that facilitate rapid and effective stem cell differentiation. Three-dimensional (3D) hierarchical microarchitectures have been developed to enable rapid neural differentiation of multipotent human mesenchymal stromal cells (HMSCs) via mechanotransduction. However, low cell viability during long-term culture and poor cell recovery efficiency from the architectures were also observed. Such problems hinder further applications of the architectures in stem cell differentiation. Here, we present improved 3D nanostructured microarchitectures functionalized with cell-adhesion-promoting arginylglycylaspartic acid (RGD) peptides. These RGD-functionalized architectures significantly upregulated long-term cell viability and facilitated effective recovery of differentiated cells from the architectures while maintaining high differentiation efficiency. Efficient recovery of highly viable differentiated cells enabled the downstream analysis of morphology and protein expression to be performed. Remarkably, even after the removal of the mechanical stimulus provided by the 3D microarchitectures, the recovered HMSCs showed a neuron-like elongated morphology for 10 days and consistently expressed microtubule-associated protein 2, a mature neural marker. RGD-functionalized nanostructured microarchitectures hold great potential to guide effective differentiation of highly viable stem cells.

Original language	English (US)
Pages (from-to)	41030-41037
Number of pages	8
Journal	ACS Applied Materials and Interfaces
Volume	11
Issue number	44
DOIs	https://doi.org/10.1021/acsami.9b13694
State	Published - Nov 6 2019

Funding

The research reported in this publication was supported, in part, by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Natural Sciences and Engineering Research Council of Canada (grant no. RGPIN-2016-06090). This research is part of the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. acknowledges financial support from the University of Toronto Connaught Fund.

Keywords

RGD peptides
electrodeposition
mechanobiology
nanostructured microarchitecture
neural differentiation
stem cell bioengineering

ASJC Scopus subject areas

General Materials Science

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abstract = "Microenvironmental factors play critical roles in regulating stem cell fate, providing a rationale to engineer biomimetic microenvironments that facilitate rapid and effective stem cell differentiation. Three-dimensional (3D) hierarchical microarchitectures have been developed to enable rapid neural differentiation of multipotent human mesenchymal stromal cells (HMSCs) via mechanotransduction. However, low cell viability during long-term culture and poor cell recovery efficiency from the architectures were also observed. Such problems hinder further applications of the architectures in stem cell differentiation. Here, we present improved 3D nanostructured microarchitectures functionalized with cell-adhesion-promoting arginylglycylaspartic acid (RGD) peptides. These RGD-functionalized architectures significantly upregulated long-term cell viability and facilitated effective recovery of differentiated cells from the architectures while maintaining high differentiation efficiency. Efficient recovery of highly viable differentiated cells enabled the downstream analysis of morphology and protein expression to be performed. Remarkably, even after the removal of the mechanical stimulus provided by the 3D microarchitectures, the recovered HMSCs showed a neuron-like elongated morphology for 10 days and consistently expressed microtubule-associated protein 2, a mature neural marker. RGD-functionalized nanostructured microarchitectures hold great potential to guide effective differentiation of highly viable stem cells.",

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author = "Zongjie Wang and Libing Zhang and Mahmoud Labib and Haijie Chen and Mingyang Wei and Mahla Poudineh and Green, {Brenda J.} and Bill Duong and Jagotamoy Das and Sharif Ahmed and Sargent, {Edward H.} and Kelley, {Shana O.}",

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AU - Green, Brenda J.

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Peptide-Functionalized Nanostructured Microarchitectures Enable Rapid Mechanotransductive Differentiation

Abstract

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Keywords

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