In-vivo assessment of a tissue engineered vascular graft computationally optimized for target vessel compliance

Tissue engineered vascular grafts (TEVGs) have the ability to be tuned to match a target vessel's compliance, diameter, wall thickness, and thereby prevent compliance mismatch. In this work, TEVG compliance was manipulated by computationally tuning its layered composition or by manipulating a crosslinking agent (genipin). In particular, these three acelluluar TEVGs were compared: a compliance matched graft (CMgel - high gelatin content); a hypocompliant PCL graft (HYPOpcd- high polycaprolactone content); and a hypocompliant genipin graft (HYPOgen - equivalent composition as CMgel but hypocompliant via increased genipin crosslinking). All constructs were implanted interpositionally into the abdominal aorta of 21 Sprague Dawley rats (n = 7, males=11, females=10) for 28 days, imaged in-vivo using ultrasound, explanted, and assessed for remodeling using immunofluorescence and two photon excitation fluorescence imaging. Compliance matched grafts remained compliance-matched in-vivo compared to the hypocompliant grafts through 4 weeks (p <0.05). Construct degradation and cellular infiltration was increased in the CMgel and HYPO gen TEVGs. Contractile smooth muscle cell markers in the proximal anastomosis of the graft were increased in the CMgel group compared to the HYPOpd (p = 0.007) and HYPOgen grafts (p = 0.04). Both hypocompliant grafts also had an increased pro-inflammatory response (increased ratio of CD163 to CD86 in the mid-axial location) compared to the CMgel group. Our results suggest that compliance matching using a computational optimization approach leads to the improved acute (28 day) remodeling of TEVGs. To the authors' knowledge, this is the first in-vivo rat study investigating TEVGs that have been computationally optimized for target vessel compliance. Statement of significance Coronary artery bypass surgery is generally performed by harvesting a vessel from the patient, but this vessel is commonly unavailable due to widespread disease. Another option is the tissue engineered vascular graft (TEVG) which can be fabricated from synthetic and native biopolymers to create a tubular structure similar to the vasculature. While these TEVGs have had limited success, the mechanical properties of the grafts are often overlooked and tend to be overly stiff compared to the native vessel. An overly stiff TEVG can cause the graft to narrow and eventually clot or fail. This study aims to evaluate the effect of stiffness, compliance, on TEVG design. Stiff and compliant grafts were implanted into a rat model and evaluated for cellular infiltration and migration. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study demonstrates the importance of compliance matching in tissue engineered vascular grafts (TEVGs) for improved acute remodeling. Compliance matched grafts showed better performance in vivo compared to hypocompliant grafts, resulting in reduced inflammation and improved cellular infiltration. The use of computational optimization approaches in designing TEVGs enhances their mechanical properties and overall success in coronary artery bypass surgery.