John Ashton PhD Candidate Biomedical Engineering GIDP 2008 Stanford AAA Summit September 4-5, 2008, Stanford, CA “Development of a Thrombus Mimic for Drug Delivery Studies of Abdominal Aortic Aneurysms” John Ashton (1), Darren Haskett (2), Bruce Simon (1,3), Jonathan Vande Geest (1,3,4) (1) Biomedical Engineering (2) Agriculture and Bio Systems Engineering (3) Aerospace and Mechanical Engineering (4) Bio5 Institute The University of Arizona

Introduction
Abdominal aortic aneurysm (AAA) is a significant disease in developed countries. While currently available clinical treatments (surgical repair and endovascular repair) are relatively successful, they are only performed on larger AAAs in which rupture risk outweighs the procedure risk. It would be advantageous to develop a drug treatment that impedes AAA growth for patients which have smaller AAAs, instead of periodically monitoring AAA growth until it reaches high rupture risk. In addition, such treatment could be used in patients with large AAAs who are ineligible for current treatments. One such drug under investigation by others is doxycycline. An intraluminal thrombus (ILT) is present in the majority of AAAs and often covers a large portion of the inner surface of the AAA. The wall covered with ILT is weaker than wall not covered by AAA, and therefore it is essential that a drug locally delivered from the lumen is able to reach wall covered by ILT. Development of a thrombus mimic with similar components, structure, and mechanical properties as native ILT would facilitate AAA drug delivery investigations as it would provide a more abundant test medium and less sample variability.

Experimental Aim
The elastic modulus, water content, and structure of thrombus mimics constructed from blood components were compared to native ILT from AAAs.

Work Summary
Native ILT specimens were obtained from AAA surgical repair and divided into three layers based on coloration: abluminal, medial and luminal. Four groups of thrombus mimics were constructed by mixing various concentrations of fibrinogen, thrombin, and calcium. Elastic modulus was measured by performing compressive stress-relaxation tests at 5% strain, based on equilibrium load. Water content was found by measuring the volume of water loss from saline-saturated samples which dried for 12 hours. Scanning electron microscopy (SEM) images were taken to compare structure.

Results
The abluminal layer had the highest elastic modulus (19.3 kPa) and there was no statistical difference between the medial layer, luminal layer, and one of the mimics (2.5, 1.5, and 1.0 kPa, respectively). Concentrations of fibrinogen, thrombin, and calcium significantly affected the elastic modulus of the thrombus mimics. Water content of the ILT (79%) was less than that of the thrombus mimics (95%). SEM images showed that native ILT and thrombus mimics have similar structure.

Conclusions
One of the thrombus mimics is comparable to the ILT’s medial and luminal layers. Elastic modulus of the mimics can be manipulated by varying the components’ concentrations. Currently, we are measuring and comparing the permeability of ILT and mimics. Our future work is to model the ILT and mimics as porohyperelastic materials to understand fluid flows through the ILT of an AAA, which will aid in developing local drug delivery strategies.