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Intra-thoracic fibrous tissue induction by polylactic acid and epsilon-caprolactone copolymer cubes, with or without slow release of basic fibroblast growth factor

^a Second Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
^b Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Received 1 May 2007; received in revised form 29 June 2007; accepted 13 July 2007.

^_* Corresponding author. Address: Second Department of Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Tel.: +81 87 891 2191; fax: +81 87 891 2192. (Email: yokomise{at}kms.ac.jp).

Objective: We investigated whether implantation of polylactic acid and epsilon-caprolactone copolymer (PLAC) cubes with or without basic fibroblast growth factor (b-FGF) released slowly from gelatin microspheres was able to induce fibrous tissue in the dead space remaining after pneumonectomy in the thoracic cavity. Methods: Left pneumonectomy was performed in Japanese white rabbits. In the control group (n = 6), the left thoracic cavity was closed without any treatment. In the FGF group (n = 6), gelatin microspheres that released 100 µg of b-FGF were implanted into the left thoracic cavity. In the PLAC group (n = 6), PLAC cubes were implanted into the left thoracic cavity. In the PLAC/FGF group (n = 6), both PLAC cubes and gelatin microspheres releasing 100 µg of b-FGF were implanted into the left thoracic cavity. Results: In the control and FGF groups, herniation of the heart, mediastinal shift, and overinflation of the right lung were observed. No granular tissue formation was observed. In the PLAC and PLAC/FGF groups, a dense area of newly formed soft tissue was observed, and only a mild mediastinal shift was observed during the 3-month follow-up period. Pathological examination revealed induction of fibrous and granular tissue in the left thoracic cavity. The foreign-body reaction induced by PLAC was very mild. Conclusions: Implantation of PLAC cubes with or without gelatin microspheres releasing 100 µg of b-FGF is able to induce fibrous tissue in the post-pneumonectomy dead space.

Key Words: Polylactic acid cubes • Epsilon-caprolactone copolymer cubes • Basic fibroblast growth factor • Gelatin microspheres • Thoracic cavity • Fibrous tissue • Granular tissue