Long-term remodeling of compliance matched tissue engineered vascular grafts is sex specific

Compliance matching of tissue engineered vascular grafts (TEVGs) is a promising technique to combat common failure modes seen clinically in small diameter vascular procedures like coronary artery bypass grafting (CABG). However, despite the influence of sex on vascular response to injury, the role of biological sex on the success of TEVG innovations such as compliance matching, namely in long-term remodeling, has been understudied. In this study we fabricated compliance matched TEVGs (CM TEVGs) and hypocompliant TEVGs (Hypo TEVGs) by adjusting the thicknesses of a high polyester urethane urea (PEUU) containing layer (80:20 PEUU:Gelatin) and a low PEUU containing layer (20:80 PEUU:Gelatin). All grafts were implanted into the abdominal aorta of both male and female Sprague Dawley rats (n = 4) as interposition grafts for 6 months and monitored using in vivo ultrasound. Upon explant, key outcomes of long-term remodeling were assessed via immunohistochemistry, multiphoton imaging, and qRT-PCR. CM TEVGs were confirmed to be compliance matched to native aorta both in vitro and in vivo upon implant. After remodeling, CM TEVGs had increased degradation and decreased calcification compared to Hypo TEVGs. CM TEVGs had increased mature VSMC genes (Acta2, Myh11, Cnn1) in males and decreased macrophage presence (CD68) in females. Independent of graft type, females had increased intimal thickening, decreased luminal presence of mature VSMCs, and increased fibrillar collagen deposition compared to males in both CM and Hypo TEVGs. Our results suggest that long-term remodeling outcomes in response to compliance matching are dependent on biological sex at both the tissue and cellular level.