A facile 3D bio-fabrication of customized tubular scaffolds using solvent-based extrusion printing for tissue-engineered tracheal grafts.

Abstract

Tracheal implantation remains a major therapeutic challenge due to the unavailability of donors and the lack of biomimetic tubular grafts. Fabrication of biomimetic tracheal scaffolds of suitable materials with matched rigidity, enhanced flexibility and biocompatibility has been a major challenge in the field of tracheal reconstruction. In this study, customized tubular grafts made up of FDA-approved polycaprolactone ( <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PCL</mi></mrow> </math> ) and polyurethane ( <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PU</mi></mrow> </math> ) were fabricated using a novel solvent-based extrusion 3D printing. The printed scaffolds were investigated by various physical, thermal, and mechanical characterizations such as contact angle measurement, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), radial compression, longitudinal compression, and cyclic radial compression. In this study, the native goat trachea was used as a reference for the fabrication of different types of scaffolds (cylindrical, bellow-shaped, and spiral-shaped). The mechanical properties of the goat trachea were also compared to find suitable formulations of <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PCL</mi> <mo>/</mo> <mi>PU</mi></mrow> </math> . Spiral-shaped scaffolds were found to be an ideal shape based on longitudinal compression and torsion load maintaining clear patency. To check the long-term implantation, in vitro degradation test was performed for all the 3D printed scaffolds and it was found that blending of <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PU</mi></mrow> </math> with <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PCL</mi></mrow> </math> reduced the degradation behavior. The printed scaffolds were further evaluated for biocompatibility assay, live/dead assay, and cell adhesion assay using bone marrow-derived human mesenchymal stem cells (hMSCs). From biomechanical and biological assessments, <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>PCL</mi> <mn>70</mn> <mo>/</mo> <mi>PU</mi> <mn>30</mn></mrow> </math> of spiral-shaped scaffolds could be a suitable candidate for the development of tracheal regenerative applications.