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Injury-on-a-chip for modelling microvascular trauma-induced coagulation
Halston Deal1,2, Elizabeth M Byrnes1, Sanika Pandit1,2
1Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, 1840 Entrepreneur Dr., Raleigh, NC, 27695 USA. mdaniel6@ncsu.edu.
Lab on a Chip
|January 7, 2025
Summary
A new pressure injury-on-a-chip (PINCH) device visualizes blood coagulation at vascular endothelium injury sites. Pre-treating endothelium with shear stress improves the capture of this critical injury response, aiding therapeutic evaluation.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Hemostasis Research
Background:
- Blood coagulation is a vital injury response involving fibrin polymerization to seal damaged endothelium.
- Existing microfluidic systems struggle to replicate and assess coagulation as a direct response to vascular endothelium disruption.
- Monitoring coagulation in response to injury is crucial for understanding hemostasis and developing therapeutics.
Purpose of the Study:
- To develop a novel microfluidic device for inducing and visualizing localized vascular endothelium injury.
- To assess blood coagulation dynamics specifically at the site of induced injury.
- To evaluate the efficacy of pre-conditioning vascular endothelium with fluid shear stress on capturing coagulation responses.
Main Methods:
- Introduction of a pressure injury-on-a-chip (PINCH) device to create controlled compression injuries in microfluidic vascular endothelium models.
- Utilizing fluorescently labeled fibrin to visualize and quantify coagulation accumulation at injury sites.
- Applying fluid shear stress to vascular endothelium prior to injury to assess its impact on coagulation response.
- Testing the device's utility in modeling hemophilia A and evaluating hemostatic and fibrinolytic nanoparticles.
Main Results:
- The PINCH device successfully visualizes and quantifies fibrin accumulation, representing coagulation, at the site of microvascular injury.
- Pre-treatment of vascular endothelium with fluid shear stress significantly enhances the capture of coagulation as an injury response.
- The device demonstrated the impaired coagulation response in a model of type A hemophilia.
- Evaluation of hemostatic microparticles and fibrinolytic nanoparticles was successfully performed using the PINCH system.
Conclusions:
- The PINCH device provides a robust platform for studying localized blood coagulation in response to vascular endothelium injury.
- Fluid shear stress pre-conditioning is a valuable strategy for improving the fidelity of coagulation assessment in microfluidic injury models.
- The PINCH device is a promising tool for screening hemostatic therapeutics and studying bleeding disorders like hemophilia.
