Publication Date

Summer 2023

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Mechanical Engineering

Advisor

Sang-Joon Lee; Lin Jiang; Anand Ramasubramanian

Abstract

Blood clots are a leading contributor to deaths and cardiovascular complications; however, they also play a critical role in wound healing. Though treatments inhibiting platelet activity help prevent thrombosis, they also affect the contractile forces exerted by platelets and, potentially, their distribution. The stiffness of the fibrin matrix that maintains the clot structure is also affected. The hypothesis of this investigation is that blood clots with uniform platelet distribution exhibit higher resistance to deformation than clots with clustered distributions, specifically because of local strain stiffening by platelets. The hypothesis was tested by conducting finite element analysis (FEA) simulations of platelet-rich plasma (PRP) clots, modeled as two platelet aggregates in a fibrin matrix undergoing uniaxial tension. An amplified modulus function that diminishes radially away from each platelet was prescribed for the surrounding fibrin to account for local matrix stiffening. Spatial distribution of platelets was characterized by using Ripley’s K-function to quantify the extent of particle clustering, and the simulation was validated by comparing the stress-strain curves to those of experimental PRP clots. As platelet aggregates were arranged less uniformly in the clot, the stiffness of the clot decreased by 25%. However, when local matrix stiffening was disabled, clot stiffness slightly increased (< 5%). These findings could inform the development of in vitro clot assays to better mimic the distribution of platelet aggregates of in vivo clots.

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