Invited commentary

Abstract

A major obstacle limiting the success of vascular conduit placement remains the limited ability to obtain endothelial coverage of the graft luminal surface. Among the beneficial functions of a confluent endothelium are thromboresistance, selective permeability, and interactions with circulating blood elements and underlying smooth muscle. Clinical and laboratory results show that large-diameter high-flow systems tolerate the use of conduits that lack an endothelial lining. That is not the case for small caliber systems and systems that have slower flow. Conduits with slow blood flow and smaller-caliber conduits perform poorly due to thrombotic complications, possibly due to the lack of nitric oxide and prostacyclin and the longer interaction of the blood elements with the nonendothelialized luminal surface. This study and others like it focus on defining methods for creating a conduit that has a confluent luminal endothelial lining that tolerates placement in the circulation. The scaffold, matrix or material of the graft, and the source and conditions under which the endothelial cells are harvested and placed on the conduit are important in determining the degree of success in achieving endothelial confluence and the durability of the endothelial layer when challenged with flow conditions. The authors have demonstrated clearly that, in the short term, the more complex culture conditions of cyclic shear stress produce an endothelial graft lining that functions in a manner superior to that produced by conditions of steady shear stress at low or high levels. Improvement in endothelial function with cyclic shear stress was noted in terms of maintenance of integrity of the endothelial layer and inhibition of adhesion of circulating blood elements to the luminal surface of the graft. The authors observed by Western blotting increased expression of endothelial nitric oxide synthase and prostaglandin I synthase in the cyclic shear stress conduits compared with the conduits created under other conditions. Defining the role of these or other biologic molecules in conferring favorable graft function will require formal investigation. The functional performance characteristics of the endothelial lining of a conduit likely are the result of many factors, one of which appears to be the type of shear stress used when creating the endothelial monolayer. Other factors may include the scaffold, the origin of the endothelial cells and their culture conditions, both biologic and mechanical. The ideal conduit for certain applications may also include smooth muscle cells along with endothelial cells to allow for a more durable structure or potentially for biologic molecule delivery via vascularized structures that have genetically engineered cells designed to deliver physiologic regulatory molecules locally or to the circulation. Patterns of molecular expression that may be expected to yield favorable endothelial performance characteristics might possibly include robust eNOS expression and decreased expression of tissue factor and other unfavorable candidate molecules. Additional work, including longer-term studies and studies in arterial-arterial grafts is required to adequately address the challenge of adequate conduit design. The fate of an endothelium layer after preconditioningJournal of Vascular SurgeryVol. 51Issue 1PreviewA strategy in minimizing thrombotic events of vascular constructs is to seed the luminal surface with autologous endothelial cells (ECs). The task of seeding ECs can be achieved via bioreactors, which induce mechanical forces (shear stress, strain, pressure) onto the ECs. Although bioreactors can achieve a confluent layer of ECs in vitro, their acute response to blood remains unclear. Moreover, the necessary mechanical conditions that will increase EC adhesion and function remain unclear. We hypothesize that preconditioning seeded endothelium under physiological flow will enhance their retention and function. Full-Text PDF Open Archive