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J. Fredrik Grimmer, MD; Chad B. Gunnlaugsson, MD; Eben Alsberg, PhD; Hedwig S. Murphy, MD, PhD; Hyun Joon Kong, PhD; David J. Mooney, PhD; Robert A. Weatherly, MD

Arch Otolaryngol Head Neck Surg. 2004;130:1191-1196.

Objectives  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 bioabsorble 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.

From the Departments of Otolaryngology (Drs Grimmer, Gunnlaugsson, and Weatherly) and Biomedical Engineering (Drs Alsberg, Kong, and Mooney), University of Michigan, Ann Arbor; and Department of Pathology and Laboratory Medicine, Veterans Affairs Ann Arbor Health System (Dr Murphy). Dr Grimmer is now with Children's Hospital Boston, Boston, Mass. Dr Weatherly is now with the Department of Otolaryngology, University of Kansas, Kansas City. The authors have no relevant financial interest in this article.

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