Tranilast-loaded tubular scaffold and surgical suture for suppression of stenosis after tracheal prosthesis transplantation

Abstract

Most tracheal prosthesis implantation fail because of restenosis at the anastomotic site. Tranilast, which is approved as an anti-allergic drug, has been found to inhibit the proliferation of fibroblasts. In this study, use of a tracheal scaffold and surgical suture loaded with tranilast was proposed. A three-dimensionally printed tubular scaffold was designed as an artificial tracheal implant, both ends of which were fixed with surgical sutures. The formation of granulation tissue at both ends of the scaffold were compared among four animal groups that were transplanted with a drug-loaded or bare scaffold and sutured with drug-loaded or bare thread. In animal models with a tracheal defect, the inhibitory effect of tranilast on stenosis at an anastomotic site was observed to be synergistically enhanced when both the scaffold and suture were loaded with tranilast, allowing for better survival after tracheal implantation. Histologic evaluation also revealed that more M2 phenotype macrophages, which are known to be responsible for anti-inflammation and tissue regeneration, were recruited around the scaffold than pro-inflammatory M1 macrophages that otherwise would stimulate fibrosis. Therefore, these results suggest that tracheal implantation using a tubular scaffold and suture, both loaded with tranilast, is a promising strategy for suppression of tracheal stenosis.