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Updated: Jun 23, 2026

Platelet-Derived Extracellular Vesicle Functionalization of Ti Implants
Published on: August 5, 2021
Titanium implants alter endothelial function and vasoconstriction via a protein kinase C-regulated pathway.
Rong Sen Yang1, Huei Ping Tzeng, Feng Ming Ho
1Department of Orthopedics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Elevated titanium (Ti) levels from joint prostheses may impair blood vessel function. This study found Ti exposure reduced aortic contractions and altered key proteins involved in vascular signaling.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Orthopedic Surgery
Background:
- Titanium (Ti) alloy is widely used in orthopedic reconstruction for joint prostheses.
- Elevated serum Ti concentrations are observed in patients with loosened knee prostheses.
- The precise circulatory effects of elevated Ti remain unclear.
Purpose of the Study:
- To investigate the impact of titanium on vascular endothelial function and contractility.
- To elucidate the molecular mechanisms underlying titanium's effects on blood vessels.
Main Methods:
- Assessing maximal contractile responses to phenylephrine in rat aortas post-Ti alloy implantation and in cultured aortas treated with soluble Ti.
- Analyzing protein expression and phosphorylation of endothelial nitric oxide synthase (eNOS), protein kinase C (PKC)-alpha, and extracellular signal-regulated kinase (ERK) 1/2 in aortic tissues and HUVECs.
- Utilizing PKC inhibitors to investigate signaling pathways.
Main Results:
- Ti alloy implantation and soluble Ti treatment significantly decreased maximal contractile responses in rat aortas.
- Enhanced protein expression of eNOS and PKC-alpha, and increased ERK1/2 phosphorylation were observed in Ti-exposed aortas.
- Soluble Ti dose-dependently increased eNOS expression and enhanced phosphorylation of eNOS, PKC, and ERK1/2 in HUVECs.
- PKC inhibitors attenuated Ti-induced phosphorylation of eNOS and PKC.
Conclusions:
- Circulating titanium may alter endothelial function by modulating eNOS, PKC, and ERK signaling pathways.
- These alterations in endothelial function can lead to reduced vasoconstriction.
- Findings suggest potential vascular complications associated with elevated titanium levels from prostheses.
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