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Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models
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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
PubMed
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.

Keywords:
Calcified artery modelMechanical testingTissue engineered vascular grafts

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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.