Bioengineered vascular access maintains structural integrity in response to arteriovenous flow and repeated needle puncture.
OBJECTIVE
Tissue-engineered blood vessels (TEBV) have been proposed as an alternative to prosthetic grafts for dialysis access. However, arteriovenous (AV) grafts must withstand extreme flow rates and frequent needle trauma. In a proof-of-concept study, we sought to determine whether scaffold-based TEBV could withstand the hemodynamic and mechanical challenges of chronic dialysis access.


METHODS
TEBV were constructed using decellularized arterial scaffolds seeded with autologous ovine endothelial cells (EC) derived from circulating endothelial progenitor cells (EPC) using a novel high-affinity capture approach. Seeded scaffolds were preconditioned to arterial pressure and flow in a bioreactor for 2 weeks prior to implantation to create carotid artery to jugular vein AV grafts in each animal. TEBV were healed for 1 month before initiating percutaneous needle puncture 3 days/week. TEBV wall geometry and patency were monitored using duplex imaging and were either explanted for histologic analysis at 2 months (n = 5) or followed for up to 6 months until venous outflow stenosis threatened AV graft patency (n = 6).


RESULTS
Despite high flow, TEBV maintained stable geometry with only modest wall dilation (under 6%) by 4 months after implantation. Needle access was well tolerated with a single puncture site complication, a small pseudoaneurysm, occurring in the late group. Time-to-hemostasis at puncture sites averaged 4 ± 2 minutes. Histologic analysis at 2 months demonstrated repopulation of the outer TEBV wall by host cells and healing of needle punctures by cellular ingrowth and new matrix deposition along the tract. TEBV followed beyond 2 months showed stable wall geometry but, consistent with the primary mode of clinical AV graft failure, all TEBV eventually developed venous anastomotic stenosis (mean, 4.4 ± 0.9 months; range, 3.3-5.6 months postimplantation; n = 6).


CONCLUSIONS
This pilot study supports the concept of creating dialysis access from scaffold-based autologous TEBV. Engineered AV grafts were created within a clinically relevant time frame and demonstrated stable wall geometry despite high flow and repeated puncture. Cellular ingrowth and puncture site healing may improve wall durability, but venous outflow stenosis remains the primary mode of TEBV graft failure in the ovine model.
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Bryan W
BW
Tillman
Saami K
SK
Yazdani
Lucas P
LP
Neff
Matthew A
MA
Corriere
George J
GJ
Christ
Shay
S
Soker
Anthony
A
Atala
Randolph L
RL
Geary
James J
JJ
Yoo
D015901:Angiography, Digital Subtraction; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects / Q000295:instrumentation*; D019149:Bioreactors; D001794:Blood Pressure; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D042783:Endothelial Cells / Q000637:transplantation*; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D006083:Graft Occlusion, Vascular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D006439:Hemodynamics; D007601:Jugular Veins / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008422:Materials Testing; D023421:Models, Animal; D009339:Needles; D010865:Pilot Projects; D011474:Prosthesis Design; D011475:Prosthesis Failure; D011673:Pulsatile Flow; D011677:Punctures; D012039:Regional Blood Flow; D006435:Renal Dialysis; D012756:Sheep; D033581:Stem Cell Transplantation; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D018615:Ultrasonography, Doppler, Color; D018617:Ultrasonography, Doppler, Pulsed; D014654:Vascular Patency