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 D

Poster E2 - Modulating the Compliance of Varied Thrombogenicity Vascular Graft Designs

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Heart disease remains the leading cause of mortality in the United States, with coronary artery disease (CAD) resulting in approximately 610,000 deaths annually [1]. Coronary artery bypass grafts (CABG) are a common treatment option for CAD, with approximately 400,000 implantations performed each year [2]. Unfortunately, CABG procedures exhibit a substantial failure rate of 42.8% [3]. This high rate is believed to be influenced by biomechanical compliance mismatches between native blood vessels and grafts, leading to outcomes such as intimal hyperplasia and thrombosis [4]. Addressing these challenges through the development of anti-thrombogenic compliant small-diameter tissue-engineered vascular grafts (TEVGs) holds promise for significantly enhancing patient outcomes.
In this work, we sought to develop two tunable small diameter compliance matched, trilayer TEVG designs. Both grafts have identical middle and outer layers. Poly(lactide-co-caprolactone) (PLCL) was selected as a primary material due to its high elasticity and lack of toxic byproducts. The outer layers incorporate a significant amount of gelatin to promote cellular infiltration and remodeling. One variant includes an anti-thrombogenic inner layer of poly(ester urethane)urea elastomer containing sulfobetaine (PESBUU-50) [5], whereas the other features a thrombogenic inner layer of PLCL. These graft designs will enable assessment of the benefits conferred by the anti-thrombogenic inner layer.

Materials and

Methods:  Our chosen TEVG polymer mixtures were composed of gelatin isolated from porcine skin (MilliporeSigma), PESBUU-50, and 60:40 PLCL (MilliporeSigma). Trilayered grafts were fabricated by electrospinning solutions of either 8% PESBUU-50 or 10% PLCL, then 10% 80:20 PLCL:Gelatin,
then 10% 40:60 PLCL:Gelatin. The solutions were dissolved in 1,1,1,3,3,3-Hexafluoro-2-propanol. The PESBUU-50 solution was electrospun at +20 kV and -4 kV. All other solutions were electrospun at a voltage difference of +15 kV, and -5 kV. Solutions were dispensed onto a rotating target mandrel of 1.1 mm diameter at a working distance of 10 cm. Grafts were crosslinked for 24 hours in 0.5% genipin in 200 proof ethanol at 37°C. The compliance of the grafts was modulated by changing the volume dispensed into the inner two layers. The grafts were then mechanically tested using a custom microbiaxial optomechanical device (CellScale) (Figure 1) that pressurized the samples from 5 mmHg to 120 mmHg in a 37°C heated water bath across 10 cycles, imaging the TEVG outer diameters at a frequency of 5 Hz. Grafts diameters and thicknesses were measured by cutting a cross section and measuring using an Olympus Surgical Microscope. Compliance was calculated using the outer diameters on the 10th testing cycle at 70 mmHg and 120 mmHg [4]. The resulting compliance values were compared to the range of those obtained from native rat aorta explants. Compliance matched (CM) values were those that fell within the range of native aortas. Grafts with values below this range were considered hypocompliant (stiff).

Results, Conclusions, and Discussions: The native rat aortas were determined to have a mean of 0.00139 mmHg-1. The CM TEVG design with PLCL inner layer had an average compliance of 0.00136 mmHg-1, while the CM PESBUU-50 inner layer design had an average of 0.00130 mmHg-1. The hypocompliant design with a PLCL inner layer had an average compliance of 0.00074 mmHg-1, while the hypocompliant design with PESBUU-50 inner layer design had an average of 0.00072 mmHg-1 (Figure 3). The native rat aortas had an average wall thickness of 85 µm, while the CM and hypocompliant PLCL TEVG designs had wall thicknesses of 156.4 µm and 174.5 µm, respectively. The compliance matched PESBUU-50 inner layer design had a wall thickness of 188.3 µm, while the hypocompliant design has a wall thickness of 155.2 µm (Figure 4).
These results showed that a small diameter PLCL and PESBUU-50 trilayered graft can be compliance matched to rat aorta explants. Additionally, by modifying the volume dispensed into the inner and middle layers, hypocompliant grafts were fabricated, demonstrating that the compliance of these grafts can be modulated. Future work includes the development of hypercompliant versions of both grafts, as well as further biomechanical characterization of the TEVGs. In addition, both in vitro and in vivo studies will be performed to evaluate the impact of the PESBUU-50 inner layer on the anti-thrombogenicity of the grafts.

Acknowledgements (Optional):  This research was funded by NIH award R01HL157017 to JPVG and SURI program at the Swanson School of Engineering and the Office of the Provost at the University of Pittsburgh.

REFERENCES
1. Tsao, et al. Circulation 147, 2023.
2. Bachar, et al. StatPearls, 2023.
3. Hess, et al. Circulation 130, 2014.
4. Jeong, et al. Biomaterials Science 8.16, 2020.
5. Ye, et al. ACS Applied Mat. & Int. 6.24, 2014.