Invited commentary

Abstract

The goal of developing a small-caliber, prosthetic vascular graft comparable to autologous vein conduit remains elusive. More than 30 years ago, Dr Alexander Clowes and his group observed that excessive intimal hyperplasia associated with exuberant smooth muscle cell and endothelial cell proliferation occurred in anastomotic stenosis of polytetrafluoroethylene bypass grafts. Over time, this phenomenon has been attributed to factors such as compliance mismatch between the prosthetic graft and the native artery, vascular wall sheer stress, and response to injury. Despite a variety of adjunctive techniques, such as the Linton patch and Miller cuff, to improve patency associated with prosthetic bypass grafts, a lack of an endothelialized luminal wall limits effectiveness of these prosthetic grafts. An intact endothelial monolayer limits the proliferative wound healing response seen after vascular wall injury. One approach that has proved to be challenging has been seeding the graft with endothelial progenitor cells or anti-CD34 antibodies to encourage growth of a luminal endothelial layer. Tissue engineering, the process of combining cells and biologically active molecules on a biologic scaffold, holds great promise in designing functional and durable bioprosthetic vascular grafts. Research in this field has focused on properties of the biologic scaffold, techniques for seeding the scaffold with cells, and methods to facilitate the incorporation of circulating cells after the scaffold is implanted. Weber et al have developed a small-caliber bioprosthetic vascular graft with sufficient tensile and suture retention strength to withstand the high pressures typical of arteries. Unlike other bioprosthetic grafts that require preimplantation seeding with progenitor cells, the bacterial nanocellulose (BNC) graft has surface properties designed to attract autologous cells after implantation, thereby providing a scaffold for cells to be organized into a vascular wall-like structure. Moreover, the BNC is nonimmunogenic, causing minimal inflammatory reaction. Development of an optimal BNC graft that has durable patency as a small-vessel conduit continues to evolve. The first-generation BNC graft, as previously described by Wippermann et al in 2009 and Scherner et al in 2014, facilitated incorporation of cells into the familiar three layers of the native artery, with endothelial cells lining the luminal side of the graft. However, the first-generation graft was hindered by 50% graft thrombosis rate at 4 weeks, originating from perianastomotic thrombus that was likely secondary to compliance mismatch. In the second-generation BNC graft described in the current volume of the Journal of Vascular Surgery, Weber et al have improved their earlier graft by fabricating a significantly thinner-walled, more flexible material, thus alleviating compliance mismatch without compromising tensile strength. Unfortunately, in optimizing the mechanical properties of the bioprosthetic graft, the cellular structure was compromised. The newer graft supported only the ingrowth of fibroblasts, and there was no endothelial lining. Nonetheless, improving the mechanical properties of the graft improved patency. The group should be commended for their perseverance and methodical approach to this pervasive problem. Having followed this group's progress in identifying properties conducive to recruiting endothelial cells and developing a scaffold with optimal mechanical characteristics, we look forward to the development of their next-generation bioprosthetic graft. Each step forward in this area brings us closer to the elusive “Holy Grail” of vascular surgery—a clinically viable small-caliber bioprosthetic vascular graft. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Patency and in vivo compatibility of bacterial nanocellulose grafts as small-diameter vascular substituteJournal of Vascular SurgeryVol. 68Issue 6PreviewDespite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential. Full-Text PDF Open Archive