(516g) Maturation of Implantable Vascular Grafts in An Ovine Model Using Small Intestinal Sub-Mucosa: Do We Need Pre-Seeding of Smooth Muscle Cells?

The purpose of this study is to engineer vascular grafts which have the ability to grow, remodel and function normally within the host. Tissue engineered arterial substitutes with cell-seeded biomaterial scaffolds have been proven to perform better at the blood-material-interface as compared to synthetic alternatives.  In this study, we aim to study the time-dependent process of host cell migration, maturation and remodeling of graft tissue with fully functional and implantable arterial grafts made from hair follicle derived smooth muscle cells (HF-SMC), ovine pulmonary artery endothelial cells on a scaffold of Small Intestinal Submucosa (SIS). Early events of immune responses and fibrotic tissue formation around the implanted vessels as well as cell seeding effect on long-term patency and functionality of SIS based vessels are reported.

SIS sheets were rolled into tubular constructs with fibrin glue using a previously optimized technique (Peng 2011, Cell, Tissue and Organ).  Using a customized bioreactor, arterial shear stress was achieved within our constructs using optimized parameters sustaining patency of our grafts with the use of an arterio-venous shunt bypass model that we developed in our laboratory. SIS grafts, with or without initial seeding of HF-SMC were evaluated when implanted as an inter-positional carotid graft in an ovine model at 1, 4 and 12 weeks.

The implanted tissues were monitored biweekly using Doppler ultrasound to document patency and measure blood flow rates through the grafts. At 1, 4 and 12 weeks we also performed angiography, which confirmed uniform bilateral blood flow rates through the carotids.  We observed early cellularization of graft by host (before the 1 month time point starting at 1 week), followed by differentiation and maturation of permeated host cells, which remodel the TEVs in-vivo. Our data directly correlate with functionality and mechanical properties of explanted grafts. Over time in the host, SIS grafts developed architecture similar to native artery and vascular functionality due to infiltration of host cells.

The patency of the grafts and their capacity for remodeling and development of vascular function suggest that this approach is very promising and may be of clinical significance. Our grafts exhibited structural and functional properties similar to native artery and provided appropriate chemo-attractant signals for maturation in-vivo in a time-dependent manner. Biomaterial vascular grafts thus made provide an implantable arterial replacement for vascular regeneration, with potential for off-the-shelf design.