Autologous and synthetic vascular grafts trigger different host responses in the anastomotic regions and in the perivascular adipose tissue during the early healing phase

Interactions between tissue and material post-implantation significantly impact the long-term behavior of vascular prostheses. Autologous materials are preferred for replacing small-diameter blood vessels due to their superior healing properties compared to synthetic options. This study aimed to characterize the host response to autologous and various synthetic grafts <i>in vitro</i> and <i>in vivo</i> during the early healing phase, focusing on anastomotic regions and perivascular adipose tissue (PVAT). Immune cell activation by seeding human macrophages and neutrophils onto decellularized umbilical cord arteries (dUCAs), biodegradable thermoplastic polyether-urethane (TPU/TPUU), and expanded polytetrafluoroethylene (ePTFE) grafts was assessed <i>in vitro</i>. Autologous aortic grafts, TPU/TPUU, and ePTFE grafts were implanted in rats to evaluate cytokine expression in anastomotic regions at 24 h and 1 week, alongside protein and gene expression analyses of PVAT. Decellularized UCA grafts elicited less pro-inflammatory macrophage activation than ePTFE and TPU/TPUU <i>in vitro</i>. Autologous grafts exhibited no inflammatory response in anastomotic regions, while ePTFE displayed significantly higher cytokine and pro-inflammatory gene expression at 24 h after implantation. TPU/TPUU specimens showed a delayed response. PVAT analyses revealed significant inflammation in ePTFE implants, contrasting with limited pro-inflammatory activation in autologous and TPU/TPUU grafts. Significant differences in the upregulation of inflammatory cytokines and pro-inflammatory genes can be observed in the early postoperative healing phase. Therefore, new synthetic materials or therapeutic approaches targeting inadequate healing response at the early stage would be mandatory to overcome current graft performance limitations. In particular, the role of PVAT in vascular graft healing should be evaluated in detail.