Effect of Locally Applied Transforming Growth Factor Beta3 on Wound Healing and Stenosis Development in Tracheal Surgery

Abstract

BACKGROUND: Tracheal stenosis constitutes one of the most frequently seen problems in thoracic surgery. Although many treatment modalities to prevent fibroblast proliferation, angiogenesis, or inflammation that causes tracheal stenosis have been attempted, an effective method has not yet been found. In this study, a transforming growth factor beta3 (TGF-␤3)/chitosan combination was used for this purpose. METHODS: A slow-release preparation containing a thin layer of TGF-␤3 with a chitosan base was made. Thirty albino Wistar rats were divided into 3 groups. A full-layer vertical incision was made in the anterior side of the trachea of each rat between the second and fifth tracheal rings. The tracheal incision was sutured. Group A was evaluated as the control group. In Group B, a chitosan-based film was placed on the incision line. In Group C, a slow-release TGF-␤3/chitosan-coated substance was placed on the incision line. The rats were killed on day 30, and their tracheas were excised by cutting between the lower edge of the thyroid cartilage and the upper edge of the sixth tracheal ring together with the esophagus. Epithelialization, fibroblast proliferation, angiogenesis, inflammation, and collagen levels were evaluated histopathologically by the same histopathologist. RESULTS: Statistically significant differences were not found among the 3 groups. Cold abscesses were observed at the incision sites in both the TGF-␤/chitosan and chitosan groups. These were thought to have formed due to the chitosan. CONCLUSIONS: As this was the first experiment in the literature to use this type of TGF-␤3 formulation, we intend to change the formulation and perform this study again with a different TGF-␤3/chitosan preparation.

Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

“…Tracheal stenosis is a pathological scar in which the inflammatory phase of cicatrization is prolonged and TGF- β 1 production and collagen synthesis and deposition in the ECM are increased [4, 7], which causes fibrosis at the lesion site [5, 6]. TSs are treated with endoscopic and surgical procedures combined with topical WHM application (e.g., MMC) to pharmacologically manipulate ECM formation and prevent tracheal restenosis.…”

“…The following three isoforms of TGF- β have been described: TGF- β 1, TGF- β 2, and TGF- β 3; the first two isoforms (TGF- β 1 and TGF- β 2) are profibrogenic, whereas TGF- β 3 is anti-inflammatory and antifibrotic. The three isoforms are present in all wound-healing stages, particularly in the proliferative and remodeling phases [3, 5], and the therapeutic modulation of this factor may prevent fibrotic scarring [6]. …”

Effects of transforming growth factor-beta-1 neutralizing antibody and transforming growth factor-beta-3 on the development of tracheal stenosis

“…However, a previous study reported a tissue reaction when using slow-release preparations containing TGF-b3 at a dose of 1 µg combined with chitosan. [12] This decreased the effectiveness of the film formations. Therefore, we used new preparations to ensure tissue compatibility.…”

Tracheal Repair with Human Umbilical Cord Mesenchymal Stem Cells Differentiated in Chondrocytes Grown on an Acellular Amniotic Membrane: A Pre-Clinical Approach

“…When the defect exceeds these limits, it has been tried to replace the trachea using organic and artificial tubes that unfortunately causes severe complications such as infection, extrusion, obstruction, stenosis and chronic rejection [3]. Studies have suggested that the regeneration of the trachea through growth factors in platelet-rich plasma (PRP), such as platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β), promotes tissue rejuvenation and tissue repair [4,5]. However, there are many obstacles to overcome, such as the rapid degradation of growth factors [6].…”