TNF-α-licensed exosome-integrated titaniumaccelerated T2D osseointegration by promoting autophagy-regulated M2 macrophage polarization.
Biochem Biophys Res Commun
; 727: 150316, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-38959732
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Autofagia
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Titanio
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Oseointegración
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Factor de Necrosis Tumoral alfa
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Diabetes Mellitus Tipo 2
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Exosomas
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Macrófagos
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
/
Biochem. biophys. res. commun
/
Biochemical and biophysical research communications
Año:
2024
Tipo del documento:
Article
País de afiliación:
China