Human acellular dermis seeded with autologous fibroblasts enhances bronchial anastomotic healing in an irradiated rodent sleeve resection model.

Abstract

The combination of neoadjuvant radiochemotherapy and parenchyma-preserving sleeve resection for lung cancer remains controversial because of potentially increased rate of anastomotic breakdown. We analyzed the effects of applying a decellularized human dermis transplant seeded with autologous fibroblasts in a rodent sleeve resection model with neoadjuvant radiotherapy. A total of 64 male Fisher rats underwent a transsection and surgical anastomosis of the left main bronchus and were randomized to receive plus/minus radiation treatment and plus/minus augmentation of the anastomosis with a fibroblast-seeded dermis transplant (2 × 2 factorial design). A μCT scan was performed at postoperative days 7 and 14, and the animals were sacrificed on day 14. Anastomotic bursting pressure and hydroxyproline concentration were measured. In the irradiated groups, the anastomotic bursting pressure was significantly higher in the augmented group at day 7 (100.9 ± 18.3 vs 141.3 ± 18.0 kPa, p = 0.0005) but not at day 14. Hydroxyproline levels showed a similar pattern in the irradiated group with significant differences at day 7 (7 days postoperative 158 ± 11.6 vs 198.2 ± 10.9 nmol/mg, p < 0.0001) but not at day 14 postoperatively. Augmentation of a bronchial anastomosis by a dermal matrix, seeded with autologous, viable fibroblasts improves early wound breaking strength. Fibroblast-enhanced dermal matrices provide a new and easily usable tool to prevent early anastomotic leakage after neoadjuvant chemoradiation in locally advanced lung cancer.