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

Autor: Yang Y; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Wang J; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China., Lin X; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Zhang Z; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Zhang M; Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510055, China., Tang C; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Kou X; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China. Electronic address: kouxiaoxing@mail.sysu.edu.cn., Deng F; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. Electronic address: dengfl@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Oct 01; Vol. 727, pp. 150316. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.bbrc.2024.150316
Abstrakt: 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-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory 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-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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