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Microfluidic Perfusable Pathological Vasculature for Atherosclerosis Drug Screening.

Jing Liu1,2, Mulan Zhu1,2, Na Bai1,2

  • 1The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong 523059, China.

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Summary

A new 3D perfusable atherosclerotic vessel-on-a-chip (3D-PAVoC) platform better models atherosclerosis (AS) by including blood flow. This advanced model accurately predicts anti-AS drug efficacy, bridging the gap between lab tests and animal studies.

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Drug Discovery

Background:

  • Current in vitro atherosclerosis models lack physiological relevance due to the absence of blood flow.
  • This limitation hinders accurate replication of endothelial injury and drug transport dynamics in atherosclerosis (AS) development.

Purpose of the Study:

  • To develop a 3-dimensional perfusable atherosclerotic vessel-on-a-chip (3D-PAVoC) platform that incorporates hemodynamic forces.
  • To establish a more physiologically relevant in vitro model for studying AS and evaluating anti-atherosclerotic drug efficacy.

Main Methods:

  • Engineered a flow-enabled arterial construct integrating endothelial and smooth muscle cells.
  • Exposed the construct to inflammatory and hyperlipidemic stimuli to induce AS-prone conditions.
  • Evaluated drug responses using rapamycin (RAP) and validated findings in ApoE knockout mice.

Main Results:

  • The 3D-PAVoC platform demonstrated flow-dependent endothelial responses and more pronounced AS pathology compared to static models.
  • Drug efficacy testing in 3D-PAVoC showed higher RAP half-maximal inhibitory concentration, correlating better with in vivo results.
  • In vivo validation in ApoE-/- mice confirmed partial alleviation of AS progression by the identified RAP dose.

Conclusions:

  • The 3D-PAVoC platform offers a superior in vitro model for atherosclerosis research by incorporating crucial hemodynamic factors.
  • This model enhances the prediction of anti-atherosclerotic drug efficacy, improving the translation of in vitro findings to in vivo outcomes.
  • The platform provides valuable insights into drug mechanisms under realistic vascular and pathological conditions.