Mechanism of Exosomes Involved in Osteoimmunity Promoting Osseointegration Around Titanium Implants With Small-Scale Topography

Abstract

Exosomes are nanoscale extracellular vesicles. Several studies have shown that exosomes participate in intercellular communication and play a key role in osseointegration. However, it is unclear whether exosomes and their contents participate in the communication between the immune and skeletal systems in the process of osseointegration. In this study, we obtained smooth titanium disks by polishing and small-scale topography titanium disks by sandblasted large-grit acid-etched (SLA) technology combined with alkali thermal reaction. After stimulating mouse RAW264.7 cells with these two kinds of titanium disks, we co-cultured the MC3T3-E1 cells and the RAW264.7 cells, obtained and identified the exosomes derived from RAW264.7 cells, and studied the effect of the osteoimmune microenvironment and the exosomes on the osseointegration of mouse MC3T3-E1 cells. Cell counting kit-8 (CCK-8), real time quantitative PCR, western blotting, alizarin red staining, and quantitative and confocal fluorescence microscopy were used to study the effects of exosomes on MC3T3-E1 cells; RNA sequencing and correlation analysis were performed. We found that the osteoimmune microenvironment could promote the osseointegration of MC3T3-E1 cells. We successfully isolated exosomes and found that RAW264.7 cell-derived exosomes can promote osteogenic differentiation and mineralization of MC3T3-E1 cells. Through RNA sequencing and gene analysis, we found differentially expressed microRNAs that targeted the signal pathways that may be related, such as mTOR, AMPK, Wnt, etc., and thus provide a reference for the mechanism of osteoimmunue regulation of implant osseointegration. The study further elucidated the mechanism of implant osseointegration and provided new insights into the effect of exosomes on implant osseointegration, and provided reference for clinical improvement of implant osseointegration and implant success rate.

Modifying a 3D-Printed Ti6Al4V Implant with Polydopamine Coating to Improve BMSCs Growth, Osteogenic Differentiation, and In Situ Osseointegration In Vivo

“…In general, based on a WCA >90° or <90°, a surface could be classified as hydrophobic (low SFE) or hydrophilic (high SFE). And at WCA >150° or <5°, the surface could be further defined as super-hydrophilic and super-hydrophobic ( Wei et al, 2020 ; Han and Gong 2021 ; Zhang et al, 2021 ). As presented in Figure 1F , the water contact angle of 3D-PDA was obviously lower than that of the 3D group, which suggested that the surface of the 3D-PDA group had better hydrophilicity and higher SFE.…”

Osteoimmune Interactions and Therapeutic Potential of Macrophage-Derived Small Extracellular Vesicles in Bone-Related Diseases

“…Moverover, several miRNAs involved in the progress of osseointegration were upregulated or downregulated, indicating that M2-sEVs played an important role in the process of osteoimmunity-promoting osseointegration. 40 Another study confirmed that sEVs extracted from macrophages cultured with titania nanotube arrays anodized with a voltage of 40 V (TNA-40) can significantly upregulate the ALP activity and osteogenic-related gene expression of BMSCs, promote endothelial cell (EC) migration, and enhance angiogenic capacity through the interaction between miR-3473e and the target gene Akt1. 41 The immunosuppressive and anti-inflammatory molecule ADA2AR has been proven to enhance the proliferation and migration of vascular endothelial cells (VECs) and promote angiogenesis and the selection of M-sEVs during bone healing.…”

Plant-Derived Exosome-like Nanoparticles for Biomedical Applications and Regenerative Therapy

“…Exosome-loaded hydroxyapatites were reported to promote calvaria bone regeneration, as shown by the enhanced counts of bone-forming fibroblasts, fibrocytes, osteoblast, osteocytes, and osteons, as well as the promoted expression of osteopontin [ 234 , 235 ]. In addition to hydroxyapatites, poly (lactic- co -glycolic acid) or PLGA [ 236 ], titanium [ 237 , 238 , 239 ], and β-tricalcium phosphate (β-TCP) [ 240 ] have been reported to be successfully applied in exosome-based bone tissue engineering, whether as a scaffold or an implant material [ 241 ]. These materials enhanced cellular migration toward the scaffold, then promoted cellular interaction and adhesion, leading to acceleration of osteogenic events [ 237 ].…”