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

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.

The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation

“… 6 , 8 , 42 Our previous study demonstrated that the SLM-AHT surface with hierarchical microgroove/nanopore topography could promote preosteoblast MC3T3-E1 cells osteogenic differentiation by enhancing integrin α2-related cell adhesion. 43 In the current study, we revealed that the SLM-AHT surface could not only enhance osteogenic differentiation of PDLSCs but also inhibit adipogenic differentiation. Nevertheless, the mechanotransduction mechanism of SLM-AHT surface directing cell fate remains to be elucidated.…”

“… 10 Then, we upgraded the preparation protocol and fabricated titanium surfaces with microgrooves/nanoporous hierarchical topography by selective laser melting (SLM) combined with alkali heat treatment (AHT), and our preliminary study suggested that this topography might be more effective in promoting the osteogenic differentiation of preosteoblast MC3T3-E1 cells than that of other surfaces. 11 However, the underlying mechanism of hierarchical micro/nanoscale topography-mediated direction of stem cell differentiation remains unclear.…”

Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants

“…It had been proven that the bioactivity of SLM dental implants, including in vitro mesenchymal stem cells adherence, proliferation, differentiation, and in vivo osseointegration could be improved by the hierarchical micro-nano topography ( Ferraris et al, 2011 , 2019 ; Gulati et al, 2017 ; H. Wang et al, 2018 ; Yu et al, 2018 ). An up to date research had verified that the osteogenesis promoting effect of nanomodified SLM implants was strongly related to the integrin α2-PI3K-AKT signaling axis ( Zheng et al, 2020 ). Today, SLM titanium surfaces could be nanomodified via anodization ( Gulati et al, 2017 ), hydrothermal (H. Wang et al, 2018 ; Yu et al, 2018 ), or inorganic chemical treatments ( Ferraris et al, 2011 , 2019 ).…”

“…Wang et al, 2018;Yu et al, 2018). An up to date research had verified that the osteogenesis promoting effect of nanomodified SLM implants was strongly related to the integrin α2-PI3K-AKT signaling axis (Zheng et al, 2020). Today, SLM titanium surfaces could be nanomodified via anodization (Gulati et al, 2017), hydrothermal (H. Wang et al, 2018;Yu et al, 2018), or inorganic chemical treatments (Ferraris et al, 2011(Ferraris et al, , 2019.…”

Self-agglomerated collagen patterns govern cell behaviour

“…Integrin signalling is one of the first steps upon cell attachment and initiates downstream signalling cascades for cellular responses such as cell adhesion, growth, motility, shape, and differentiation 47 . Integrins are transmembrane proteins that modulate cell-biomaterial crosstalk by interacting www.nature.com/scientificreports/ their extracellular domain with the ECM and the intracellular domain with signalling molecules and can be activated by both surface topography [48][49][50] and surface chemistry [51][52][53] . However, it is still under debate whether cells react initially to surface chemistry 54,55 or surface topograpy 55,56 .…”