Sustained local application of epidermal growth factor to accelerate reepithelialization of tracheal grafts

Objective

Epidermal growth factor–loaded gelatin microspheres were tested for potential to accelerate tracheal allograft reepithelialization.

Methods

Epidermal growth factor–loaded gelatin microspheres were prepared by optimal double-phase emulsified condensation polymerization. One hundred age-matched allogeneic mice were randomly allocated to local administration of 1 mg epidermal growth factor–loaded gelatin microspheres (containing 1 μg epidermal growth factor), 1 mg gelatin microspheres, 1 μg epidermal growth factor, or nothing (control, all groups n = 25) during orthotopic transplant of C57BL/6 donor tracheal segments into BALB/c recipients without immunosuppressors. On days 7, 14, 21, 35, and 52 after transplant, 5 mice per group were killed and evaluated by histologic assessment and scanning electronic microscopy for reepithelialization and fibrosis of tracheal grafts.

Results

Mean diameter of gelatin microspheres was 107 μm. Microspheres could not be fully degraded until 35 days after transplant in vivo. On days 7, 14, and 21, epithelium score and ratio of lamina propria to tracheal cartilage were not statistically different between mice with epidermal growth factor–loaded gelatin microspheres and other groups. On days 35 and 52, however, epithelium score was higher and ratio of lamina propria to tracheal cartilage was lower in epidermal growth factor–loaded gelatin microsphere recipients; these mice also had almost complete differentiation of regenerated epithelium into ciliated columnar epithelium on days 35 and 52, earlier than in other groups.

Conclusions

Gelatin microspheres act as a functional vector for epidermal growth factor. Sustained local application of epidermal growth factor could accelerate reepithelialization of tracheal allografts.

CTSNet classification: 15.9

Abbreviations and Acronyms: EGF, epidermal growth factor, EGF-GM, epidermal growth factor–loaded gelatin microsphere, ES, epithelium score, GM, gelatin microsphere, LCR, ratio of lamina propria to tracheal cartilage, PBS, phosphate-buffered saline solution