Surface Topography Regulates Osteogenic Differentiation of MSCs via

Oct 6, 2017 - The response of mesenchymal stem cell (MSCs) to elaborate microarchitectured topographies in three-dimensional environment and the under...
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Surface topography regulates osteogenic differentiation of MSCs via crosstalk between FAK/MAPK and ILK/#catenin pathways in a hierarchically porous environment Haoyi Niu, Dan Lin, Wei Tang, Yifan Ma, Bing Duan, Yuan Yuan, and Changsheng Liu ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/acsbiomaterials.7b00315 • Publication Date (Web): 06 Oct 2017 Downloaded from http://pubs.acs.org on October 18, 2017

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ACS Biomaterials Science & Engineering

Surface topography regulates osteogenic differentiation of MSCs via crosstalk between FAK/MAPK and ILK/β-catenin pathways in a hierarchically porous environment

Haoyi Niu1,2, Dan Lin1, Wei Tang3, Yifan Ma1, Bing Duan2, Yuan Yuan1,2*, Changsheng Liu1,2*

1

Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key

Laboratory of Bioreactor Engineering, East China University of Science and Technology,

Shanghai 200237, PR China 23

Engineering Research Center for Biomaterials of Ministry of Education, East China

University of Science and Technology, Shanghai 200237, PR China

Full mailing address of authors: East China University of Science and Technology, 130

Meilong Road, Shanghai 200237, PR China

Email address of the corresponding author: [email protected] (Yuan Yuan);

[email protected] (Changsheng Liu)

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Abstract:

The response of mesenchymal stem cell (MSCs) to elaborate micro-architectured

topographies in three-dimensional environment and the underlying molecular mechanism

remain poorly understood. Here, with hierarchical mesoporous bioactive glass (MBG)

scaffolds as substrate model, we show the effects of specific, elaborate micro-textured

topographies (micrograiny, microporous and hybrid micrograiny/microporous surface) on

MSCs osteogenesis and the molecular mechanism involved. With a similar size and density,

the microporous surface was more favorable for the MSCs osteogenesis, and the hybrid

micrograiny/microporous surface exhibited a synergetic effect. All the micro-scaled

topographies facilitated expression of integrin subunits, focal adhesion complexes and

up-regulated FAK/MAPK and ILK/β-catenin signaling pathways. Separately blocking

FAK/MAPK and ILK/β-catenin cascade dramatically attenuated the heightened β-catenin

signaling, and the phosphorylation of ERK1/2 and P38, respectively, indicating a typical

crosstalk between FAK/MAPK and ILK/β-catenin signalings was involved. Correlating the

MSCs response with the specific topographical cues, it can be inferred that the

micrograiny/microporous topographies induced FAs assembly and homeostasis, and thus

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ACS Biomaterials Science & Engineering

FAK/MAPK and ILK/β-catenin signalings played critical role in regulating MSCs osteogenic

differentiation. The findings, therefore, have significant implications in better understanding

of the MSCs fate in a 3D environment and provided guidance of the development of novel

biomaterial for bone regeneration.

Keywords: micrograiny/microporous topography, indirect mechanotransduction, signaling

crosstalk, MSCs osteogenic differentiation

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1. Introduction

A great increase of bone defects caused by disease, trauma, together with multiple limitations

associated with the autografts, have imperatively raised the request for synthetic bone

substitutes in recent years

1-2

. It is becoming increasingly clear that a crucial event in bone

regeneration process is to in situ create a favorable extracellular microenvironment for

triggering the differentiation of mesenchymal stem cells (MSCs) into bone-forming

osteoblasts, which directly participate in subsequent formation and maturation of bone tissue 3-4

. Therefore, understanding how a MSC perceives the surrounding micro-environmental

cues and then initiates an osteogenic transformation is critical for design of the bone

substitutes. Although, the substrate-mediated osteogenesis is a complex process, micro-scales

topographical cues (0.5-10 µm) is considered as the most attractive and effective strategy to regulate this process and ultimately determine the long-term performance of material in vivo 3, 5-13

. Seo et al.’s

9

and Li Z’s studies 5, for example, found that osteogenic differentiation of

MSC was up-regulated by tailor-made micropit and micro-pillar surfaces respectively.

Moreover, several studies have shown that incorporation of microporosity (