Abstract
Recently our group demonstrated that acellular tissue engineered vessels (A-TEVs) comprised of small intestinal submucosa (SIS) immobilized with heparin and vascular endothelial growth factor (VEGF) could be implanted into the arterial system of a pre-clinical ovine animal model, where they endothelialized within one month and remained patent. Here we report that immobilized VEGF captures blood circulating monocytes (MC) with high specificity under a range of shear stresses. Adherent MC differentiate into a mixed endothelial (EC) and macrophage (Mφ) phenotype and further develop into mature EC that align in the direction of flow and produce nitric oxide under high shear stress. In-vivo, newly recruited cells on the vascular lumen express MC markers and at later times they co-express MC and EC-specific proteins and maintain graft patency. This novel finding indicates that the highly prevalent circulating MC contribute directly to the endothelialization of acellular vascular grafts under the right chemical and biomechanical cues.
Highlights
Our group demonstrated that acellular tissue engineered vessels (A-TEVs) comprised of small intestinal submucosa (SIS) immobilized with heparin and vascular endothelial growth factor (VEGF) could be implanted into the arterial system of a pre-clinical ovine animal model, where they endothelialized within one month and remained patent
In our lab we developed an acellular vascular graft that was based on small intestinal submucosa (SIS) with immobilized heparin and VEGF on the graft lumen to capture VEGF receptor expressing cells from the blood
We show that VEGF captures MC, which significantly outnumber endothelial progenitor cells (EPCs) in the blood, and differentiate into functional endothelial cell (EC) that produces nitric oxide and affords patency to neo-arteries
Summary
Our group demonstrated that acellular tissue engineered vessels (A-TEVs) comprised of small intestinal submucosa (SIS) immobilized with heparin and vascular endothelial growth factor (VEGF) could be implanted into the arterial system of a pre-clinical ovine animal model, where they endothelialized within one month and remained patent. In addition to decellularized grafts, nonbiological grafts composed of various polymeric biomaterials have been used to engineer cell-free vascular grafts[16,17,18,19,20,21,22,23,24] All of these acellular materials must promote endothelialization of the lumen to achieve patency and promote development of the vascular wall through extensive, long-term remodeling. We show that VEGF captures MC, which significantly outnumber endothelial progenitor cells (EPCs) in the blood, and differentiate into functional EC that produces nitric oxide and affords patency to neo-arteries
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