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

Abstract

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 (CM_gel - high gelatin content); a hypocompliant PCL graft (HYPO_pcl - high polycaprolactone content); and a hypocompliant genipin graft (HYPO_gen - equivalent composition as CM_gel 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 CM_gel and HYPO_gen TEVGs. Contractile smooth muscle cell markers in the proximal anastomosis of the graft were increased in the CM_gel group compared to the HYPO_pcl (p=0.007) and HYPO_gen 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 CM_gel 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.