Tracheal reconstruction using tissue-engineered cartilage.
OBJECTIVE
To determine whether rabbit cartilage can be tissue engineered using a polyglycolic acid (PGA) construct composed of PGA mesh, autologous chondrocytes, and alginate covalently linked with the cell adhesion sequence arginine-glycine-aspartic acid (RGD), and to investigate the feasibility of reconstructing tracheal defects using the PGA construct in conjunction with a bioabsorbable intratracheal stent.


METHODS
Nineteen New Zealand White rabbits were used. Nine rabbits underwent subcutaneous implantation of 3 different PGA construct combinations: (1) PGA, autologous chondrocytes, and RGD-modified alginate; (2) PGA, autologous chondrocytes, and unmodified alginate; and (3) PGA and RGD-modified alginate. The remaining 10 animals underwent anterior tracheal reconstruction using fascia lata grafts and the complete PGA construct (PGA, autologous chondrocytes, and RGD-modified alginate). At the time of tracheal reconstruction, a poly-l-lactic acid intratracheal stent was placed in 5 of these latter animals. Rates of tracheal stenosis and mortality were compared with those of historical control animals. Histologic analysis was performed on the PGA constructs.


RESULTS
In the subcutaneous implants, the PGA constructs made with chondrocytes (with and without RGD) demonstrated mature cartilage formation in 7 (78%) of the 9 animals. No cartilage was seen in PGA constructs made without chondrocytes. Two of the 10 animals that underwent tracheal reconstruction with the complete PGA construct survived to 20 weeks and demonstrated patent airways, 1 with a stent and 1 without a stent (80% overall mortality). Histologic analysis showed mature cartilage formation at the tracheal reconstruction site. Historical control animals that underwent reconstruction with fascia lata alone demonstrated the lowest overall mortality.


CONCLUSIONS
Cartilage can be tissue engineered in rabbits using PGA mesh embedded with alginate-encapsulated autologous chondrocytes. It is also possible to reconstruct tracheal defects with this method of cartilage engineering, although the mortality rate in this study is high.
Grimmer
J Fredrik
JF
Department of Otolaryngology, University of Michigan, Ann Arbor, MI, USA. johannes.grimmer@tch.harvard.edu
Gunnlaugsson
Chad B
CB
Alsberg
Eben
E
Murphy
Hedwig S
HS
Kong
Hyun Joon
HJ
Mooney
David J
DJ
Weatherly
Robert A
RA
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D019902:Chondrocytes / Q000637:transplantation*; D020219:Chondrogenesis; D005240:Feasibility Studies; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D019344:Lactic Acid; D011091:Polyesters; D011100:Polyglycolic Acid; D011108:Polymers; D011817:Rabbits; D015607:Stents; D013526:Surgical Mesh; D023822:Tissue Engineering / Q000379:methods*; D014132:Trachea / Q000473:pathology / Q000601:surgery; D014182:Transplantation, Autologous
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D020723:Glucuronic Acid