Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis.

Huimin Zheng,Yingjie Yu,Xudong Wu,Zhipeng Feng,Yujuan Tian,Feng Dong,Lei Sui,Xianyou Xia,Qian Gao

doi:10.3389/fbioe.2020.00463

Abstract

Surface topography dictates important aspects of cell biological behaviors. In our study, hierarchical micro-nano topography (SLM-AHT) with micro-scale grooves and nano-scale pores was fabricated and compared with smooth topography (S) and irregular micro-scale topography (SLA) surfaces to investigate mechanism involved in cell-surface interactions. Integrin α2 had a higher expression level on SLM-AHT surface compared with S and SLA surfaces, and the expression levels of osteogenic markers icluding Runx2, Col1a1, and Ocn were concomitantly upregulated on SLM-AHT surface. Moreover, formation of mature focal adhesions were significantly enhanced in SLM-AHT group. Noticablely, silencing integrin α2 could wipe out the difference of osteogenic gene expression among surfaces with different topography, indicating a crucial role of integrin α2 in topography induced osteogenic differentiation. In addition, PI3K-AKT signaling was proved to be regulated by integrin α2 and consequently participate in this process. Taken together, our findings illustrated that integrin α2-PI3K-AKT signaling axis plays a key role in hierarchical micro-nano topography promoting cell adhesion and osteogenic differentiation.

Highlights

Surface topography is a key determinant of the cellular response to foreign materials (Chen et al, 2014; Dalby et al, 2014; Gautrot et al, 2014; Denchai et al, 2018), which is extremely important for intraosseous implants to achieve osseointegration
This study aims to investigate the role of integrin α2PI3K-AKT signaling axis in hierarchical micro-nano topography induced cell adhesion and osteogenic differentiation
Recent studies revealed that surface with nano-scale features was effective at improving osteoblasts adhesion and differentiation (Gautrot et al, 2014; Rosa et al, 2014; Huang et al, 2016; Guadarrama Bello et al, 2017; Lopes et al, 2019)

Summary

Introduction

Surface topography is a key determinant of the cellular response to foreign materials (Chen et al, 2014; Dalby et al, 2014; Gautrot et al, 2014; Denchai et al, 2018), which is extremely important for intraosseous implants to achieve osseointegration. It is noteworthy that natural bone is a loose porous multi-ordered structure composed of nano-scale collagen and hydroxyapatite and micro-scale bone plates and pores (Robling et al, 2006; Karsenty et al, 2009; Zhu et al, 2020). To mimic this environment, it is of great significance to manufacture intraosseous implants with hierarchical micro-nano surface topography (Shah et al, 2018; Cui et al, 2019; Zhang et al, 2019). The mechanisms implicated in the cell-surface interactions remain unclear

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