Development Of An Improved Vascular Graft For Use In The Arterial Circulation In Children

Sunday, October 27, 2013: 9:36 AM
Windermere Ballroom W (Hyatt Regency Orlando, formerly the Peabody)
Brooks Udelsman1, Hirotsuga Kurobe, MD2, Tai Yi, MD2, Toshiharu Shinoka, MD2 and Christopher K. Breuer2, (1)Yale University School of Medicine, New Haven, OH, (2)Nationwide Children's Hospital, Columbus, OH

Purpose: Currently available synthetic vascular grafts lack growth capacity, which limits their utility in the treatment of pediatric vascular disorders such as mid aortic syndrome.  We developed the first man made vascular graft with growth capacity and performed the first successful clinical trial evaluating the use of tissue engineered vascular grafts (TEVG) in humans as extracardiac Fontan conduits.  The TEVG is fabricated by seeding autologous bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold fabricated from polylactic acid fibers and coated with a 50:50 copolymer of polycaprolactone and polylactic acid (PLA/PCLA).  Unfortunately when this TEVG is used in the arterial circulation there is a high incidence of aneurysmal dilation and rupture that occurs over a 2 to 12 week time course.  We have developed and validated a murine aortic interposition graft model for use in developing TEVG for use in the arterial circulation.

Methods: In this investigation we created electrospun polycaprolactone (PCL) tubular scaffolds by dissolving 5wt% PCL in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) via rigorous stirring by a magnetic stir bar for 24 hours. The solution was transferred into a 60 cc syringe capped with a 20 gauge blunt needle, and loaded into a syringe pump. The syringe was dispensed at a flow rate of 5 mL/hr and a grounded target was set up at a distance of 15 cm. A mandrel with a 500 µm diameter was positioned between the needle and the target, set 13 cm from the needle tip and rotated at 5000 RPM. To begin electrospinning, a + 10 kV charge was applied to the syringe tip. All scaffolds were spun to a 150 µm wall thickness. Electrospinning the 5 wt% PCL+HFIP solution was also performed onto a slow speed mandrel using the same set up.  The solution was dispensed at 5 mL/hr and electrospun at + 12 kV onto a grounded mandrel to a wall thickness of 150 µm. Next we implanted both types of electrospun scaffolds [PCL fast (N=3) and PCL slow (N=3)] as aortic interposition grafts into 8-12 week old female SCID-bg mice using microsurgical technique.  We noninvasively evaluated graft function using serial ultrasound over a 22-week time course. 

Results: We had 0% operative morbidity and mortality rates and 100% survival rates through 22 weeks.  Ultrasound interrogation at 2, 4, 6, 8, 10, 14, 18, and 22 weeks demonstrated 100% graft patency without evidence of thrombosis, aneurysmal dilation, or thrombosis in both the PCL fast and PCL slow groups. 

Conclusions: Based on results of this ongoing pilot study we conclude that the electrospun PCL scaffold is a promising candidate for use as TEVG in the arterial circulation.  Further long-term follow-up through neovessel formation (total fiber degradation) is warranted.