Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces.

Yanhua Lan,Yi Ye,Chengxi Yan,Zhuo Chen,Qianrui Jin,Zhijian Xie,Xiaomin Zhao,Huizhi Xie

doi:10.3389/fcell.2020.583234

Abstract

Successful osseointegration involves the biological behavior of bone marrow stem cells (BMSCs) on an implant surface; however, the role of BMSC-derived extracellular vesicles (EVs)/exosomes in osseointegration is little known. This study aimed to: (i) explore the interaction force between exosomes (Exo) and cells on a titanium surface; (ii) discuss whether the morphology and biological behavior of BMSCs are affected by exosomes; and (iii) preliminarily investigate the mechanism by which exosomes regulate cells on Ti surface. Exosomes secreted by rat BMSCs were collected by ultracentrifugation and analyzed using transmission electron microscopy and nanoparticle tracking analysis. Confocal fluorescence microscopy, scanning electron microscopy, Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction techniques, and alkaline phosphatase bioactivity, Alizarin Red staining, and quantification were used to investigate the exosomes that adhere to the Ti plates under different treatments as well as the morphological change, adhesion, spread, and differentiation of BMSCs. We found that exosomes were efficiently internalized and could regulate cell morphology and promoted the adhesion, spreading, and osteogenic differentiation of BMSCs. These were achieved partly by activating the RhoA/ROCK signaling pathway. Our discovery presents a new insight into the positive regulatory effect of exosomes on the biological behaviors of BMSCs on Ti surface and provides a novel route to modify the surface of a Ti implant.

Highlights

Dental implants have become an alternative for replacing missing teeth, which are essential for patients looking to restore dental esthetics and function
All exosomes are derived from donor cells in good condition, which appeared spindle-like in shape on the tissue culture plate (Figures 2A,B)
The morphology of the bone marrow stem cells (BMSCs)-derived exosomes was first confirmed in the transmission electron microscopy (TEM) image (Figure 2E), which revealed that the exosomes were 100- to 200-nm spherical particles with a complete membrane structure and similar shape to a biconcavediscoid, fitting the recognized characteristics of exosomes

Summary

Introduction

Dental implants have become an alternative for replacing missing teeth, which are essential for patients looking to restore dental esthetics and function. BMSC-Derived Exosomes Promote Osseointegration increased exponentially, largely focusing on two aspects: abiotic methods (chemical and physical methods) based on surface engineering (Kuroda et al, 2002; Omar et al, 2016) and biotic methods (cells, polypeptide, covalent grafting, and etc.) that alter the implant surface with functional biomaterials (Zhang et al, 2011; Liu et al, 2017). The advantages of biotic implant modification, such as high osteoinduction capability, biocompatibility, and biodegradability, are required in many cases for biomedical applications (Geetha et al, 2008). It has been proven that nanoscale materials that show novel physical, chemical, and biological properties with high stability could be efficient alternatives to increased cell responses, bone conduction, and osseointegration (Wang Y. et al, 2018)

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