Exploring Perivascular Adipose Tissue Responses to Bioresorbable Thermoplastic Polyurethane Vascular Grafts

Substantial progress has been made in developing artificial small-diameter vascular grafts (SDVGs), yet the contribution of perivascular adipose tissue (PVAT) to vascular graft healing remains poorly understood. This study investigated the interaction of biodegradable thermoplastic polyurethane (TPU) SDVGs with PVAT using in vitro and in vivo models. Vascular and perivascular cells were cultured on TPU and analyzed by viability assays, immunofluorescence staining, scanning electron microscopy, quantitative polymerase chain reaction, and secretome and cell lysate analysis. TPU grafts were implanted into male Sprague Dawley rats for 1 week or 3 months (control = sham; n = 6/group) and assessed for cellularization, expression of inflammation-related genes, and adipocyte subtype markers. TPU supported viability, attachment, and phenotype preservation of in vitro-seeded cells. Immunofluorescence staining revealed increased adiponectin expression, and adipokine profiling identified 14 substantially up-regulated adipokines in TPU-seeded PVAT-derived cells. Histology showed rapid cellular coverage of grafts within 1 week of implantation, including CD34⁺ endothelial progenitor cells on the lumen. Quantitative polymerase chain reaction demonstrated compartment-specific dynamics: Inflammatory markers within the grafts changed predominantly after 3 months, whereas adjacent PVAT showed an early response with Tnfa induction already at 1 week. PVAT further displayed evidence of desirable immune modulation, with altered expression of innate (Cd11c and Arg1) and adaptive (Foxp3 and Tbet) immune response markers, alongside partial white-to-brown adipocyte remodeling. These findings highlight PVAT's central role-through adipokine secretion, adipocyte browning, and inflammation regulation-in vascular graft healing and underscore the importance of considering PVAT-driven adipokine dynamics in SDVG design to ensure long-term patency.