Abstract：
:Each year, hundreds of thousands coronary bypass procedures are performed in the US, yet there currently exists no off-the-shelf alternative to autologous vessel transplant. In the present study, we investigated the use of mouse thrombospondin-2 knockout (TSP2 KO) cells, which secrete a non-thrombogenic and pro-migratory extracellular matrix (TSP2 KO ECM), to modify small diameter vascular grafts. To accomplish this, we first optimized the incorporation of TSP2 KO ECM on decellularized rat aortas. Because MMP levels are known to be elevated in TSP2 KO cell culture, it was necessary to probe the effect of the modification process on the graft's mechanical properties. However, no differences were found in suture retention, Young's modulus, or ultimate tensile strength between modified and unmodified grafts. Platelet studies were then performed to determine the time point at which the TSP2 KO ECM sufficiently reduced thrombogenicity. Finally, grafts modified by either TSP2 KO or WT cells or unmodified grafts, were implanted in an abdominal aortic interposition model in rats. After 4 weeks, grafts with incorporated TSP2 KO ECM showed improved endothelial and mural cell recruitment, and a decreased failure rate compared to control grafts. Therefore, our studies show that TSP2 KO ECM could enable the production of off-the-shelf vascular grafts while promoting reconstruction of native vessels.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Kristofik NJ,Qin L,Calabro NE,Dimitrievska S,Li G,Tellides G,Niklason LE,Kyriakides TRdoi
10.1016/j.biomaterials.2017.06.025subject
Has Abstractpub_date
2017-10-01 00:00:00pages
63-73eissn
0142-9612issn
1878-5905pii
S0142-9612(17)30424-6journal_volume
141pub_type
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