Abstract

Background: Several approaches for the development of tracheal substitutes for the treatment of extensive tissue defects have been explored over the years. However, a completely satisfactory approach has not been achieved. Previously, we described a composite tissue engineered trachea (TET) using chondrocytes seeded onto a polyglycolic acid (PGA) fiber-mesh. This study was considered to improve the design and functionality of the TET by using a porcine decellularized aorta as the scaffold. Methods: Chondrocytes were harvested from sheep tracheal cartilage and were suspended in medium. The chondrocytes were then seeded onto PGA and incubated in vitro for 1week. A 3x4 cm piece was cut from a decellularized aorta and four 0.5x3 cm pieces were excised from one side in a comb like fashion. A silicon stent was inserted into this structure and the spaces were filled with chondrocyte seeded PGA. The three dimensional cell-polymer construct was then implanted into a subcutaneous pocket of a nude rat for 4 weeks. Both native and TET were analyzed for sulfated glycosaminoglycan (S-GAG) and hydroxyproline content, and stained for H&E, Safranin-O and Collagen Type- II antibody. Results: The improved design of TET formed new cartilage rings in the structuralconfiguration of native trachea. Furthermore, the decellularized aorta connected well to the cartilage, which provided an excellent support to the rings, as well as good flexibility to the engineered trachea. Histological evaluation of TET showed the presence of mature cartilage. S-GAG and hydroxyproline content was similar to native cartilage levels. Conclusion: This study demonstrates the feasibility of engineering a trachea with defined cartilage rings and similar flexibility to the native trachea.

Highlights

  • Experimental and clinical tracheal, bronchial repair or anastomosis began in the late 19th century [1]

  • The last decade of the 20th century saw an influx of newresearch concepts in terms of tissue engineering, which has had a revolutionary impact on the research of tracheal prosthesis [14]

  • After 4 weeks, the three-dimensional cell-polymer-aorta constructs formed a tissue engineered trachea (TET) with defined C-shape cartilage rings, which visibly recreated the structure of a normal trachea (Figure 3 A,B)

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Summary

Introduction

Experimental and clinical tracheal, bronchial repair or anastomosis began in the late 19th century [1]. Since the technique of tracheal reconstruction by end-to-endanostomosis has been used in a variety of tracheal diseases, such as stenosis,tracheomalacia, tuberculosis, traumatic injury, and malignancies [2] This established method is not appropriate for the repair of extensive lesions. In 1994 two of the first reports on the effort to engineer a trachea were made by Osada and colleagues [9] and Vacanti and colleagues [10] With different approaches, both groups were trying to recreate the cylindrical shape of the trachea, combining material and cells to make a more biocompatible tracheal replacement. This study was considered to improve the design and functionality of the TET by using a porcine decellularized aorta as the scaffold

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