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Related Experiment Video

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Bioprinted thrombosis-on-a-chip.

Yu Shrike Zhang1, Farideh Davoudi2, Philipp Walch3

  • 1Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

Lab on a Chip
|October 11, 2016
PubMed
Summary
This summary is machine-generated.

This study developed a 3D bioprinted thrombosis-on-a-chip model using human cells. The platform successfully mimics clot formation and fibrosis, offering a new tool for studying blood clots and potential treatments.

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Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Vascular Biology

Background:

  • Pathologic thrombosis is a major cause of death and disability, often resulting in incomplete clot resolution and long-term complications like post-thrombotic syndrome.
  • Understanding cellular interactions and developing effective therapeutics for thrombosis requires advanced in vitro models that replicate in vivo conditions.
  • Existing microfluidic devices have explored thrombosis hemodynamics, but a highly biomimetic model incorporating cellular interactions and fibrosis is needed.

Purpose of the Study:

  • To develop and validate a 3D bioprinted thrombosis-on-a-chip model using human cells and blood components.
  • To investigate the potential of this model to simulate thrombus formation, resolution, and the fibrotic remodeling process.
  • To establish a versatile platform for studying thrombosis pathology and evaluating therapeutic interventions.

Main Methods:

  • Utilized 3D bioprinting technology to construct microchannels lined with human endothelium within a gelatin methacryloyl (GelMA) hydrogel.
  • Infused human whole blood into the model to induce thrombus formation and tested clot dissolution using tissue plasmin activator.
  • Encapsulated fibroblasts within the GelMA matrix to observe their migration and collagen deposition, simulating fibrotic changes.

Main Results:

  • The 3D bioprinted model successfully formed thrombi from human whole blood under controlled conditions.
  • Perfusion with tissue plasmin activator demonstrated effective dissolution of non-fibrotic clots, validating the model's clinical relevance.
  • Encapsulated fibroblasts migrated into the thrombus and deposited collagen type I, recapitulating in vivo fibrotic remodeling and resemblance to the in vivo scenario.

Conclusions:

  • The developed 3D bioprinted blood coagulation model provides a highly biomimetic platform for studying thrombosis.
  • This model effectively simulates thrombus formation, resolution, and the progression of fibrosis, offering insights into post-thrombotic syndrome.
  • The versatile platform can be extended to investigate other vascularized fibrotic diseases and to screen potential therapeutic strategies.