Tissue-engineered valved conduits in the pulmonary circulation.
OBJECTIVE
Bioprosthetic and mechanical valves and valved conduits are unable to grow, repair, or remodel. In an attempt to overcome these shortcomings, we have evaluated the feasibility of creating 3-leaflet, valved, pulmonary conduits from autologous ovine vascular cells and biodegradable polymers with tissue-engineering techniques.


METHODS
Endothelial cells and vascular medial cells were harvested from ovine carotid arteries. Composite scaffolds of polyglycolic acid and polyhydroxyoctanoates were formed into a conduit, and 3 leaflets (polyhydroxyoctanoates) were sewn into the conduit. These constructs were seeded with autologous medial cells on 4 consecutive days and coated once with autologous endothelial cells. Thirty-one days (+/-3 days) after cell harvesting, 8 seeded and 1 unseeded control constructs were implanted to replace the pulmonary valve and main pulmonary artery on cardiopulmonary bypass. No postoperative anticoagulation was given. Valve function was assessed by means of echocardiography. The constructs were explanted after 1, 2, 4, 6, 8, 12, 16, and 24 weeks and evaluated macroscopically, histologically, and biochemically.


RESULTS
Postoperative echocardiography of the seeded constructs demonstrated no thrombus formation with mild, nonprogressive, valvular regurgitation up to 24 weeks after implantation. Histologic examination showed organized and viable tissue without thrombus. Biochemical assays revealed increasing cellular and extracellular matrix contents. The unseeded construct developed thrombus formation on all 3 leaflets after 4 weeks.


CONCLUSIONS
This experimental study showed that valved conduits constructed from autologous cells and biodegradable matrix can function in the pulmonary circulation. The progressive cellular and extracellular matrix formation indicates that the remodeling of the tissue-engineered structure continues for at least 6 months.
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U A
UA
Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115, USA.
Nagashima
M
M
Khalil
P N
PN
Nollert
G D
GD
Herden
T
T
Sperling
J S
JS
Moran
A
A
Lien
J
J
Martin
D P
DP
Schoen
F J
FJ
Vacanti
J P
JP
Mayer
J E
JE
D000818:Animals; D001672:Biocompatible Materials; D001698:Biomedical Engineering; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002478:Cells, Cultured; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000166:cytology; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation; D011108:Polymers; D011474:Prosthesis Design; D011664:Pulmonary Valve / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D012756:Sheep; D014261:Tricuspid Valve
D001672:Biocompatible Materials; D011108:Polymers