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  1. Abstract

    Studying and quantifying the mechanics of blood clots is essential to better diagnosis and prognosis of, as well as therapy for, thromboembolic pathologies such as strokes, heart attacks, and pulmonary embolisms. Unfortunately, mechanically testing blood clots is complicated by their softness and fragility, thus making the use of classic mounting techniques, such as clamping, challenging. This is particularly true for mechanical testing under large deformation. Here, we describe protocols for creating in vitro blood clots and securely mounting these samples on mechanical test equipment. To this end, we line 3D‐printed molds with a hook‐and‐loop fabric that, after coagulation, provides a secure interface between the sample and device mount. In summary, our molding and mounting protocols are ideal for performing large‐deformation mechanical testing, with samples that can withstand substantial deformation without delaminating from the apparatus. © 2021 Wiley Periodicals LLC.

    Basic Protocol 1: Cube‐shaped blood clot preparation

    Basic Protocol 2: Sheet‐shaped blood clot preparation

     
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  2. Free, publicly-accessible full text available July 1, 2024
  3. Constitutive models are important to biomechanics for two key reasons. First, constitutive modelling is an essential component of characterizing tissues’ mechanical properties for informing theoretical and computational models of biomechanical systems. Second, constitutive models can be used as a theoretical framework for extracting and comparing key quantities of interest from material characterization experiments. Over the past five decades, the Ogden model has emerged as a popular constitutive model in soft tissue biomechanics with relevance to both informing theoretical and computational models and to comparing material characterization experiments. The goal of this short review is threefold. First, we will discuss the broad relevance of the Ogden model to soft tissue biomechanics and the general characteristics of soft tissues that are suitable for approximating with the Ogden model. Second, we will highlight exemplary uses of the Ogden model in brain tissue, blood clot and other tissues. Finally, we offer a tutorial on fitting the one-term Ogden model to pure shear experimental data via both an analytical approximation of homogeneous deformation and a finite-element model of the tissue domain. Overall, we anticipate that this short review will serve as a practical introduction to the use of the Ogden model in biomechanics. This article is part of the theme issue ‘The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity’. 
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  4. Fibrin is the fibrous protein network that comprises blood clots; it is uniquely capable of bearing very large tensile strains (up to 200%) due to multiscale force accommodation mechanisms. Fibrin is also a biochemical scaffold for numerous enzymes and blood factors. The biomechanics and biochemistry of fibrin have been independently studied. However, comparatively little is known about how fibrin biomechanics and biochemistry are coupled: how does fibrin deformation influence its biochemistry? In this study, we show that mechanically induced protein structural changes in fibrin affect fibrin biochemistry. We find that tensile deformation of fibrin leads to molecular structural transitions of α-helices to β-sheets, which reduced binding of tissue plasminogen activator (tPA), an enzyme that initiates fibrin lysis. Moreover, binding of tPA and Thioflavin T, a commonly used β-sheet marker, were mutually exclusive, further demonstrating the mechano-chemical control of fibrin biochemistry. Finally, we demonstrate that structural changes in fibrin suppressed the biological activity of platelets on mechanically strained fibrin due to reduced α IIb β 3 integrin binding. Our work shows that mechanical strain regulates fibrin molecular structure and biological activity in an elegant mechano-chemical feedback loop, which possibly extends to other fibrous biopolymers. 
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