Skip to main content
2024 BMES Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.

Biomechanics

Biomechanics - Poster Session E

Poster P15 - In vivo characterization of a new tissue-engineered vascular graft elasticity by distensibility and pulse wave velocity measurements

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Graft replacement surgery, a prevalent remedy for coronary artery blockage, involves replacing the narrowed or obstructed portion of the artery with a graft [1]. These grafts may originate from the patient's own veins or arteries (autologous) or be synthetically produced (Tissue Engineered Vascular Graft-TEVG) [2]. While TEVGs offer more design flexibility, their frequent failures have spurred interest in graft design enhancement. A common cause of failure is the discrepancy in distensibility between the graft and the vessel, leading to potential complications like intimal hyperplasia [3]. Thus, grafts should match vessel stiffness and maintain it during the remodeling phase. Additionally, monitoring graft performance non-invasively in vivo is required to track graft performance post implant. Pulse wave velocity (PWV), which denotes the time taken for pulse pressure to travel between two points, serves as a reliable indicator of artery stiffness [4, 5]. While distensibility measurement is popular for in vivo graft stiffness tracking, its reliance on local pulse pressure, which is typically assumed based on population average, makes in vivo measurements difficult and poses implementation challenges [6]. Hence, PWV emerges as a tool to more accurately monitor graft stiffness during remodeling. Here, a biodegradable and anti-thrombogenic material-based graft has been devised and tested for efficacy in rat models based on local PWV and distensibility measurements using a clinical ultrasound device.

Materials and

Methods:  Grafts are made of three layers; internal (30 µL Polyester Sulfobetaine Urethane Urea), middle (65 ML 80:20 Polyester Urethane Urea (PEUU): Gelatin), and external (125 ML 20 PEUU: Gelatin) using electrospinning. The graft’s mechanical property was measured by inflation test from which initial PWV and distensibility are estimated from Eqs. (1.a) and (1.b) [7].
PWV=√(Eh/(ρD_d )) (1.a)
Distensibility=D_d/2Eh, (1.b)
where E is Young’s elastic modulus, h is wall thickness, ρ is blood density, and D_d is vessel diastolic diameter. Following, 13 Sprague Dawley rats (4 female/4 male/5 shams) underwent surgery and part of their abdominal aorta, a few millimeters (around 5 mm) before lower limb bifurcation, was replaced by the graft. Each week after surgery, an ultrasound scanner (Vevo 3100, 30 MHz) was used to collect blood velocity data using Pulse Wave Doppler proximal and distal to the graft, synchronized by the Electrocardiogram. The measured PWV was calculated by Eq. (2.a) [4]. Systolic and diastolic diameters of the graft were subsequently measured in the short-axis view in order to calculate distensibility using Eq. (2.b) [7].
PWV=∆x/(t_2-t_1 ) (2.a)
Distensibility=((D_s-D_d)/D_d )/(P_s-P_d ), (2.b)
where ∆x is the distance between PWD measurements, and t_1 is the time between R-wave and foot of velocity proximal to the graft and t_2 is the same measurement distal to the graft, D_s is systolic diameter, P_s is systolic pressure, and P_d is diastolic pressure. In Eq. (2.b), pulse pressure (P_s-P_d) is assumed constant and equal to 50 mmHg. All results are analyzed using repeated measure ANOVA.

Results, Conclusions, and Discussions: Average graft Young’s modulus from benchtop inflation test was 0.116 MPa which corresponds to PWV of 8.17 m/s for dry graft of average 95 µm thick and average diameter of 165 µm. However, the graft swells in vivo, and diameter may be affected by pressure from organs after implantation. This increased thickness and reduced diameter yield an estimated PWV of 6.22 m/s in the grafts based on the inflation test, which was verified in vivo (Fig. 1). Also, PWV in sham group (2-month-old) was measured to be 4.21 ± 0.37 in native arteries, which is consistent with the literature 8. Similar change in PWV and distensibility in 4 weeks is shown in Figs. 1 and 2. Resulting Young’s moduli are plotted in Fig. 3. Statistical analysis does not suggest any change in moduli (EPWV and Edistensibility) over time, while change in distensibility is significant over 4 weeks and for PWV is significant at week 3. By looking at Fig. 4, change of graft diameter over time could be a reason for discrepancy between E from PWV and distensibility. However, we expect the moduli calculated from both PWV and distensibility to be similar. The results were examined again by calculating pressure directly from flow velocity and wave speed (PWV) using Eq. (3), which follows from pulse wave theory 7, instead of assuming it to be 50 mmHg:
P_s-P_d=ρ×PWV×(V_max-V_min ), (3)
where V is the blood flow velocity measured within the graft by PWD. Re-evaluation shows a pulse pressure changing from 35-55 mmHg and gives closer values to E calculated from PWV (Fig. 5). Thus, we can conclude that assumption of constant pulse pressure may not be accurate in all measurements of distensibility. However, further investigation on the assumptions is required to figure out the reason for the remaining discrepancy in E values calculated by both methods. In conclusion, both distensibility and PWV measurements by ultrasound imaging can be used to study graft’s elasticity in vivo, if appropriate assumptions are taken into account.

Acknowledgements (Optional):  We would like to acknowledge NIH RO1 HL157017-01A1 (PI: Vande Geest) and L. H. Berenfield fellowship (Gholami) for their generous support.