Regenerative and durable small-diameter graft as an arterial conduit

Abstract

Despite significant research efforts, clinical practice for arterial bypass surgery has been stagnant, and engineered grafts continue to face postimplantation challenges. Here, we describe the development and application of a durable small-diameter vascular graft with tailored regenerative capacity. We fabricated small-diameter vascular grafts by electrospinning fibrin tubes and poly(e-caprolactone) fibrous sheaths, which improved suture retention strength and enabled long-term survival. Using surface topography in a hollow fibrin microfiber tube, we enable immediate, controlled perfusion and formation of a confluent endothelium within 3-4 days in vitro with human endothelial colony-forming cells, but a stable endothelium is noticeable at 4 weeks in vivo. Implantation of acellular or endothelialized fibrin grafts with an external ultrathin poly(e-caprolactone) sheath as an interposition graft in the abdominal aorta of a severe combined immunodeficient Beige mouse model supports normal blood flow and vessel patency for 24 weeks. Mechanical properties of the implanted grafts closely approximate the native abdominal aorta properties after just 1 week in vivo. Fibrin mediated cellular remodeling, stable tunica intima and media formation, and abundant matrix deposition with organized collagen layers and wavy elastin lamellae. Endothelialized grafts evidenced controlled healthy remodeling with delayed and reduced macrophage infiltration alongside neo vasa vasorum-like structure formation, reduced calcification, and accelerated tunica media formation. Our studies establish a small-diameter graft that is fabricated in less than 1 week, mediates neotissue formation and incorporation into the native tissue, and matches the native vessel size and mechanical properties, overcoming main challenges in arterial bypass surgery.small-diameter vascular graft | infrarenal abdominal aorta mouse model | electrospinning | hydrogel | endothelial colony-forming cells

Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction

“…Recent advances in tissue‐engineered blood vessels have enabled the modeling and improved understanding of complex biological phenomena. [ 14,15 ] Specifically, various methods to recreate critical components of the muscular remodeling have been developed to systematically study the cellular events and interactions involved in VPCs. Incorporating chemokines promoting stem cells recruitment in polymeric grafts and young cells engineered extracellular matrices have proven capable in promoting VPCs homing and myogenic differentiation.…”

Flow with variable pulse frequencies accelerates vascular recellularization and remodeling of a human bioscaffold

“…Regarding positive development of the HUV as vascular graft, the flow conditioning impacted the bulk mechanics of both CF and PMPD constructs, with burst values that significantly increased over the remodeling process going from approximately 600 mmHg for the decellularized scaffolds to approximately 890–986 mmHg for the recellularized constructs at Day 55 (6 weeks of culture). These burst pressure values remain lower than those of native tissues (human saphenous vein: 1,680–2,273 mmHg (Elliott et al, 2019; L'Heureux et al, 2006) and human artery: 2,031–4,225 mmHg (Elliott et al, 2019; L'Heureux et al, 2006)) and of vessels developed by other research groups, such as the rolled vessels developed by L'Heureux et al (>3,000 mmHg) (L'Heureux et al, 2006). However, the burst pressures obtained are superior to the pressure levels encountered in the physiological environment (normally <200 mmHg) and increased throughout the conditioning process to reach high values for a vascular graft developed in vitro based on an acellular human scaffold after a 55 days culture period, indicating the promising remodeling of the scaffold based on a vein toward an artery.…”

Future Perspectives in Small-Diameter Vascular Graft Engineering

“…M2 macrophages have been related to the tissue remodeling process, avoiding the activation of T and B cells [ 265 ]. Moreover, several research groups have observed the development of vasa vasorum, the responsible vessels for nutrient supplementation, into the transplanted vascular grafts, indicating its further proper adaptation by the studied living system [ 172 , 266 ].…”