TNF- α-licensed exosome-integrated titaniumaccelerated T2D osseointegration by promoting autophagy-regulated M2 macrophage polarization

被引：9

作者：

Yang, Yang ^{[1
]}

Wang, Jinyang ^{[1
,2
,3
]}

Lin, Xiaoxuan ^{[1
,2
]}

Zhang, Zhengchuan ^{[1
,2
]}

Zhang, Manjin ^{[4
]}

Tang, Cuizhu ^{[1
,2
]}

Kou, Xiaoxing ^{[1
,2
,3
]}

Deng, Feilong ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ, Hosp Stomatol, Guanghua Sch Stomatol, Guangzhou, Peoples R China

[2] Guangdong Prov Key Lab Stomatol, Guangzhou, Peoples R China

[3] Sun Yat Sen Univ, Hosp Stomatol, South China Ctr Craniofacial Stem Cell Res, Guanghua Sch Stomatol,Guangdong Prov Key Lab Stoma, Guangzhou 510055, Peoples R China

[4] Southern Med Univ, Stomatol Hosp, Sch Stomatol, Guangzhou 510055, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2024年 / 727卷

关键词：

Titanium implant; Type; 2; diabetes; Exosome; Macrophage; Osseointegration; CELLS; APOPTOSIS; PROLIFERATION; REPAIR;

D O I：

10.1016/j.bbrc.2024.150316

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF- alpha-treated mesenchymal stem cell (MSC) -derived exosomes onto micro/ nano -network titanium (Ti) surfaces. TNF- alpha-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of antiinflammatory cytokines and decreased secretion of pro -inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF- alpha-licensed exosomeimmobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.

引用

页数：11

共 64 条

[1]

Customizing the extracellular vesicles release and effect by strategizing surface functionalization of titanium [J].