# Computational Modeling of Device-Induced Platelet Activation and Receptor Shedding Relevant to Thrombosis and Bleeding in Device-Assisted Circulation

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $502,591

## Abstract

Although blood-contacting medical devices (BCMDs) have become lifesaving alternatives to organ
transplantation for many patients, thrombotic and bleeding events remain the most common postoperative
complications that tend to be devastating and often life-threatening. Device-induced hemostatic dysfunction is
commonly believed to be the culprit of these complications and is directly related to platelet activation and
receptor shedding associated dysfunction caused by the non-physiological shear stress (NPSS) in these
devices. Over the years, computational fluid dynamics (CFD)-aided simulation and analysis have been widely
adopted to achieve significant research efforts on device-induced platelet dysfunction. With the help of the CFD
technique, regions of abnormal NPSS and stagnant flow in blood flow paths can be precisely identified to assess
further the potential risk of thrombosis and bleeding in devices. However, the existing CFD models for predicting
shear-induced platelet activation and receptor shedding and related hemostatic complications (thrombotic and
bleeding), mainly based on the empirical models, have limited success from the device design perspective.
This proposal aims to develop a novel platelet activation model based on the art-of-state interpretation of the
platelet’s fundamental morphological change upon activation. It will be incorporated in the development of CFD
models capable of assessing in-vitro and in-vivo device-induced platelet dysfunction and associated adhesion
capacities to substrates. Numerical algorithms and implementation schemes will be developed to link shear-
induced platelet damage models to CFD variables to predict device-induced platelet dysfunction. Quantitative
adhesion capacities of device-damaged platelets to collagen, vWF, and fibrinogen could be used to represent
device-associated potentials for thrombosis and bleeding. Experiments will then be performed to validate the
CFD-based predictive modeling. Finally, a sheep study will be performed to test the CFD models for in-vivo
predictive modeling. CFD models will incorporate sheep-specific blood properties, device geometry, device
operating conditions, platelet consumption, and generation models to predict the in-vivo device-induced platelet
dysfunction and altered adhesion capacities of sheep on VADs and ECMO support. The successful completion
of this project will result in CFD-based predictive tools. These tools can be used to provide quantitative evaluation
of the performance and in-vivo biocompatibilities of BCMDs and aid the development and optimization of new
BCMDs with improved functional characteristics and biocompatibility.

## Key facts

- **NIH application ID:** 10752674
- **Project number:** 5R01HL162940-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Zhongjun Jon Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,591
- **Award type:** 5
- **Project period:** 2022-12-10 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10752674

## Citation

> US National Institutes of Health, RePORTER application 10752674, Computational Modeling of Device-Induced Platelet Activation and Receptor Shedding Relevant to Thrombosis and Bleeding in Device-Assisted Circulation (5R01HL162940-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10752674. Licensed CC0.

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