Development of a model system for preliminary evaluation of tissue-engineered vascular conduits.
OBJECTIVE
The ability to construct tissue-engineered neovessels for use as arterial or venous grafts holds great promise for the advancement of pediatric surgical disciplines. Although the feasibility of tissue engineering vascular grafts has been demonstrated, the long-term function, safety, and efficacy of these grafts as well as their capacity to grow and adapt remain largely unknown. In an attempt to further characterize and develop this technology, we used severe combined immunodeficiency beige (SCID/bg) mouse recipients, chosen because such animals accept xenogenic human cells, to create a small animal model that would allow a rapid and cost-effective preliminary evaluation of the function of tissue-engineered vascular grafts.


METHODS
Eight CB-17 SCID/bg female mice underwent vascular graft placement. Four of these mice received aortic interposition grafts, 1 mouse received an inferior vena cava interposition graft, and 3 mice underwent aortocaval graft insertion. All grafts were fashioned from decellularized ovine arteriole tissue engineering scaffolds. Grafts were evaluated for patency using clinical examination, ultrasound interrogation, and micro-computed tomography. Animals were killed at various time points after implantation, and grafts were harvested and analyzed histologically using standard hematoxylin and eosin staining.


RESULTS
All grafts were patent based on clinical examination for up to 35 days. Patency was confirmed in 5 grafts using ultrasound interrogation. Patency was confirmed in 4 grafts using micro-computed tomography. One animal that underwent arteriovenous grafting had to be euthanized secondary to high-output cardiac failure on postoperative day 2. The remaining animals were killed between postoperative days 12 and 35. Histologic evaluation of the specimens demonstrated patent grafts with cellular ingrowth into the tissue engineering scaffold.


CONCLUSIONS
From these results, we conclude that the use of the SCID/bg mouse model for preliminary evaluation of new tissue engineering methodologies for construction of vascular conduits is feasible. Use of this model has the added advantage of evaluating nonautologous and even xenograft tissues, including human cells.
Goyal
Amit
A
Department of Surgery, Yale University, New Haven, CT 06520, USA. ag359@email.med.yale.edu
Wang
Yinong
Y
Su
Haili
H
Dobrucki
Lawrence W
LW
Brennan
Matthew
M
Fong
Peter
P
Dardik
Alan
A
Tellides
George
G
Sinusas
Albert
A
Pober
Jordan S
JS
Saltzman
W Mark
WM
Breuer
Christopher K
CK
D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*