A novel delivery nanobiotechnology: engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization

Wei Liu,Feng Chen,Qing Chen,Longqing Wang,Qi Zhu,Dong Xie,Mingzhe Shao,Cheng Ye,Muyu Yu,Lili Yang

doi:10.1186/s12951-021-01015-y

Abstract

BackgroundMany patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether Exo-181b could enhance osteointegration.ResultsIn vitro, we firstly verified that Exo-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Also, we verified that the enhanced M2 polarization could indirectly promote the migration and osteogenic differentiation by secreting VEGF and BMP-2 in vitro.ConclusionsExo-181b could suppress inflammatory response by promoting M2 polarization via activating PRKCD/AKT signaling pathway, which further promoting osteogenesis in vitro and promote osteointegration in vivo.Graphic abstract

Highlights

Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice
The osteoimmunology concept indicates that the implant surface properties govern the effects of macrophages exert on osteoblasts
The identification of hBM‐Mesenchymal stem cells (MSCs) Adherence ability, tri-lineage differentiation capability as well as surface markers are deemed the basic criteria for identifying human bone marrow derived mesenchymal stem cells (hBM-MSC) and were performed in our research (Additional file 1: Figure S1)

Summary

Introduction

Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. We explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Some patients suffer from implant loosening after receiving titanium alloy internal fixation or prosthetic implants due to the excessive innate immune. The osteoimmunology concept indicates that the implant surface properties govern the effects (stimulation or inhibition) of macrophages exert on osteoblasts. Hierarchical intrafibrillarly mineralized collagen material was fabricated for inducing M2 macrophage polarization for bone regeneration [7]

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