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

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 ( PCL ) and polyurethane ( PU ) 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 PCL / PU . 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 PU with PCL 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, PCL 70 / PU 30 of spiral-shaped scaffolds could be a suitable candidate for the development of tracheal regenerative applications.

Statistical modelling and optimization of print quality and mechanical properties of customized tubular scaffolds fabricated using solvent-based extrusion 3D printing process.

Tissue-engineered tubular scaffolds offer huge potential to heal or replace the diseased organ parts like blood vessels, trachea, oesophagus and ureter. However, manufacturing these scaffolds in various scales and shapes is always challenging and requires progressive technology. Developing a flexible and accurate manufacturing method is a major developmental direction in the field of tubular scaffold fabrication. In this context, the present work presents a novel solvent-based extrusion 3D printing which allows extruding over a rotating mandrel to fabricate tubular scaffolds of polycaprolactone (PCL) and polyurethane (PU). Experimental runs were planned as per the central composite design (CCD) to evaluate the effects of input parameters like infill density, layer thickness, print speed and percentage of PU on the output responses like printing quality and mechanical characteristics. The printing quality was quantified by measuring average surface roughness of the printed scaffolds and mechanical properties were evaluated by measuring radial compressive load, and percentage of elongation. The experimental investigations revealed that printing quality was improved at higher infill densities and was deteriorated at higher print speeds and layer thicknesses. Similarly, the radial compressive load was improved with the increase in infill density and was decreased with an increase in layer thickness, print speed and percentage of PU. The percentage of elongation was found to improve at higher infill densities and percentages of PU and was reduced with an increase in layer thickness and print speed. Additionally, a multi-objective optimization using Genetic Algorithm was used to evaluate the optimum conditions to minimize surface roughness and maximizing radial compression load and percentage of elongation. Finally, a case study was performed by comparing the mechanical properties of tubular organs and scaffolds from the existing reports and results of the present work.