Development of novel layered polyglycolic acid sheet for regeneration of critical-size defect in rat trachea.

Abstract

Polyglycolic acid (PGA) sheets are difficult to adapt to the central airway because of poor durability against high air pressure. Therefore, we developed a novel layered PGA material to cover the central airway and examined its morphologic traits and functional performance as a potential tracheal replacement. A critical-size defect in rat cervical tracheas was covered with the material. Morphologic changes were bronchoscopically and pathologically evaluated. Functional performance was evaluated by regenerated ciliary area, ciliary beat frequency and ciliary transport function determined by measuring the moving distance of microspheres dropped onto the trachea (µm/s). The evaluation time points were 2 weeks, 1 month, 2 months and 6 months after surgery (n = 5, respectively). Forty rats underwent implantation, and all survived. Histological examination confirmed ciliated epithelization on the luminal surface after 2 weeks. Neovascularization was observed after 1 month, tracheal glands after 2 months and chondrocyte regeneration after 6 months. Although the material was gradually replaced by self-organization, tracheomalacia was not bronchoscopically observed at any time point. The area of regenerated cilia significantly increased between 2 weeks and 1 month (12.0% vs 30.0%; P = 0.0216). The median ciliary beat frequency significantly improved between 2 weeks and 6 months (7.12 vs 10.04 Hz; P = 0.0122). The median ciliary transport function was significantly improved between 2 weeks and 2 months (5.16 vs 13.49 µm/s; P = 0.0216). The novel PGA material showed excellent biocompatibility and tracheal regeneration both morphologically and functionally 6 months after tracheal implantation.