An investigation of airway wound healing using a novel in vivo model

Abstract

Objective: To study the amount of wound contraction and reepithelialization occurring in the healing process of full-thickness mucosal defects treated with and without mitomycin.

Study design: A new wound healing model was developed in which the tracheal mucosa was exteriorized without interference with the blood supply or with the cartilage support of the trachea. This was done by: 1) orthotopic tracheal revascularization in vascularized fascia; 2) isolation of revascularized segment after 14 days; 3) posterior longitudinal incision of revascularized segment; 4) exteriorization of tracheal mucosa with formation of anterior full-thickness mucosal defect; and 5) closure of posterior tracheal incision and reimplantation in the airway. This model was used to study airway wound healing in three groups of animals: 1) controls (revascularization, exteriorization, reimplantation) (N = 6); 2) full-thickness mucosal defect: patch defect (N = 5), circumferential defect (N = 3); and 3) full-thickness mucosal defect after topical mitomycin application: patch defect (N = 7), circumferential defect (N = 3). The animals were followed for periods varying from 2 to 4 weeks or until signs of dyspnea. The surface areas of the wounds before and after follow-up were measured. Wound healing was studied histologically on axial and longitudinal sections.

Results: Group 1: All the animals survived for 1 month. No significant difference existed between surface area of isolated trachea and of reimplanted trachea after follow-up. Group 2: Five animals (patch defects) survived for 1 month. Full-thickness mucosal defects healed by reepithelialization and by a surface area reduction of 58.9% (mean - standard deviation = 10.5). The animals with the circumferential defects showed dyspnea after an average follow-up of 14 days as a result of excessive granulation tissue formation. Group 3: Mitomycin reproducibly inhibited wound closure, yielding wounds that on average closed 56% less than controls by day 14 (P <.001). Histologic comparisons showed that mitomycin blocks angiogenesis during wound healing.

Conclusions: A wound healing model based on tracheal revascularization, isolation, and reimplantation was developed in rabbits. This model allowed us to study the healing of full-thickness mucosal defects inside the airway.