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Original research
Quantifying the mechanical and histological properties of thrombus analog made from human blood for the creation of synthetic thrombus for thrombectomy device testing
  1. William Merritt1,2,
  2. Anne Marie Holter1,2,
  3. Sharna Beahm1,2,
  4. Connor Gonzalez1,2,
  5. Timothy A Becker1,2,
  6. Aaron Tabor2,
  7. Andrew F Ducruet3,
  8. Laura S Bonsmann1,2,
  9. Trevor R Cotter2,
  10. Sergey Frenklakh4
  1. 1 Mechanical Engineering Department, Northern Arizona University, Flagstaff, Arizona, USA
  2. 2 Center for Bioengineering Innovation, Northern Arizona University, Flagstaff, Arizona, USA
  3. 3 Barrow Neurological Institute, Phoenix, Arizona, USA
  4. 4 Stryker Neurovascular Intervention, Research and Development, Fremont, California, USA
  1. Correspondence to Dr Timothy A Becker, Mechanical Engineering Depatment, Northern Arizona University, Flagstaff, AZ 86011, USA; Tim.Becker{at}nau.edu

Abstract

Background Untreated ischemic stroke can lead to severe morbidity and death, and as such, there are numerous endovascular blood-clot removal (thrombectomy) devices approved for human use. Human thrombi types are highly variable and are typically classified in qualitative terms – ‘soft/red,’ ‘hard/white,’ or ‘aged/calcified.’ Quantifying human thrombus properties can accelerate the development of thrombus analogs for the study of thrombectomy outcomes, which are often inconsistent among treated patients.

Methods ‘Soft’human thrombi were created from blood samples ex vivo (ie, human blood clotted in sample vials) and tested for mechanical properties using a hybrid rheometer material testing system. Synthetic thrombus materials were also mechanically tested and compared with the ‘soft’ human blood clots.

Results Mechanical testing quantified the shear modulus and dynamic (elastic) modulus of volunteer human thrombus samples. This data was used to formulate a synthetic blood clot made from a composite polymer hydrogel of polyacrylamide and alginate (PAAM-Alg). The PAAM-Alg interpenetrating network of covalently and ionically cross-linked polymers had tunable elastic and shear moduli properties and shape memory characteristics.

Conclusions Due to its adjustable properties, PAAM-Alg can be modified to mimic various thrombi classifications. Future studies will include obtaining and quantitatively classifying patient thrombectomy samples and altering the PAAM-Alg to mimic the results for use with in vitro thrombectomy studies.

  • thrombectomy
  • stroke
  • device

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Footnotes

  • Contributors Authors listed on this paper meet the following four criteria: (1) Provided substantial contributions to the conception, design, acquisition, analysis, or interpretation of the data. (2) Drafted or revised for intellectual content. (3) Approved the final version for publication. (4) Agreed to be accountable for all aspects of the work. These contributing authors include:. WM, AMH, SB, CG, TAB, AT, AFD, LSB, TC, and Sergey Frenklah.

  • Funding This work was supported by Stryker Neurovascular, a sponsored research agreement – grant # N/A.

  • Competing interests None declared.

  • Patient consent Obatined.

  • Ethics approval Institutional Biosafety Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Additional data from this study includes shear and elastic modulus data for: (1) male and (2) female thrombus samples as well as (3) all synthetic thrombus formulations tested across a shear rate range of 1 – 10 rad/s. A detailed MSB staining procedure is also available. Additional MSB and H&E histology images are available, including images and detailed analysis techniques for calculating fibrin content using Photoshop and ImageJ software. The corresponding author and the authors affiliated with Northern Arizona University can access the data. Data can be obtained by contacting the corresponding author (TAB).

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