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J Thorac Cardiovasc Surg 2010;140:209-215
© 2010 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

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

Jinbo Zhao, MD*, Yong Han, MD*, Zhibo Liang, MD, Zhipei Zhang, PhD, Qiang Lu, MD, Xiaolong Yan, MD, Xiaofei Li, MD*

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China

Received for publication August 15, 2009; revisions received October 13, 2009; accepted for publication October 25, 2009.

* Address for reprints: Xiaofei Li, MD, Department of Thoracic Surgery, Tangdu Hospital, Fourth Medical Military University, Xinsi Rd, Xi'an, Shaanxi 710038, China. (Email: lxfchest{at}fmmu.edu.cn).

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.

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






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