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Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models
Published on: January 27, 2023
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Biologically-engineered mechanical model of a calcified artery
Greeshma Thrivikraman1, Sandra L Johnson1, Zeeshan H Syedain1
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States.
Acta Biomaterialia
|April 20, 2020
Summary
Researchers developed a novel in vitro model of vascular calcification using engineered arterial grafts. This model mimics calcified arteries, aiding the development of new treatments for cardiovascular disease.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Tissue Engineering
Background:
- Vascular calcification is a key predictor of cardiovascular events.
- Existing in vitro models fail to replicate the mechanical and structural properties of calcified arteries, hindering therapeutic development.
Purpose of the Study:
- To create a physiologically relevant in vitro model of diffuse vascular calcification.
- To utilize biologically-engineered grafts that mimic native artery composition, structure, and mechanics.
Main Methods:
- Acellular collagenous extracellular matrix (ECM) grafts were exposed to elevated Calcium (Ca) and Phosphate (P) concentrations in cell culture medium.
- Serum concentration was varied (2% to 10%) to influence calcification extent.
- Histochemical, ultrastructural, chemical, thermal, and mechanical analyses were performed.
Main Results:
- The engineered grafts successfully underwent transmural calcification, forming deposits similar to pathological calcification.
- Increased serum concentration (up to 10%) significantly enhanced the extent and degree of calcification.
- Mechanical testing revealed up to a 16-fold reduction in arterial compliance, mirroring clinical observations in calcified arteries.
Conclusions:
- A novel, off-the-shelf in vitro model of diffuse arterial calcification has been successfully developed.
- This model accurately recapitulates the structural and mechanical characteristics of calcified arteries.
- The model provides a valuable platform for accelerating pre-clinical development of interventional devices and therapies for arterial calcification.
