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Perfusable Vascular Network with a Tissue Model in a Microfluidic Device
07:05

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Published on: April 4, 2018

A defined copper ion window coordinates multicellular responses for predictive vascular implant design.

Dan Zou1, Ping Yang2, Lang Jiang3

  • 1School of Comprehensive Health Management, Xihua University, Chengdu 610039, China.

Biochimica Et Biophysica Acta. General Subjects
|July 9, 2026
PubMed
Summary

Copper ions promote vascular healing by optimizing cellular responses within a specific therapeutic window. This study guides the design of copper-modified implants for enhanced tissue repair and reduced inflammation.

Keywords:
Cell responseConcentration gradientCopper ionTherapeutic windowVascular repair

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Area of Science:

  • Biomaterials Science
  • Vascular Biology
  • Regenerative Medicine

Background:

  • Copper ions possess pro-regenerative and antimicrobial properties beneficial for vascular applications.
  • Existing research lacks a comprehensive understanding of copper's systemic effects on vascular cells.
  • A systems-level approach is needed to elucidate copper's role in orchestrating vascular niche responses.

Purpose of the Study:

  • To systematically map copper ion dose-response relationships across key vascular cell types.
  • To identify a therapeutic window for copper ions in vascular applications.
  • To investigate the influence of delivery timing and cell-cell interactions on copper's regenerative effects.

Main Methods:

  • Systematic mapping of copper ion dose-response across five vascular cell types (endothelial cells, smooth muscle cells, macrophages, mesenchymal stem cells, fibroblasts).
  • Evaluation of copper delivery timing (post-attachment vs. co-culture seeding) and cell-cell interactions.
  • In vivo assessment of a copper-modified implant in a relevant model.

Main Results:

  • A core therapeutic window of 5-20 μM copper ions was identified.
  • This window promotes endothelial and stem cell activity, maintains smooth muscle cell quiescence, and modulates macrophage viability.
  • Copper delivery post-attachment and endothelial-stem cell crosstalk were critical for pro-regenerative outcomes.
  • In vivo implantation reduced neointimal thickness, improved endothelial coverage, and decreased inflammation.

Conclusions:

  • A systems-level understanding of copper ion effects on vascular cells was established.
  • The identified therapeutic window and delivery parameters guide the rational design of vascular implants.
  • Copper-modified implants demonstrate efficacy in vivo, validating the in vitro findings for harmonious tissue repair.