Feasibility Assessment of 3D Printing-Based Tubular Tissue Flap in a Porcine Model for Long Segmental Tracheal Reconstruction

Abstract

Background: Despite advances in tissue engineering, current clinical reconstructive options for long segment tracheal defects are limited. In this study, a 3D printing based tubular tissue flap strategy was developed for long segment tracheal reconstruction.

Method: A stent-patterned airway scaffold with sufficient radial rigidity and longitudinal bending flexibility was designed and its mechanical behavior was analyzed using finite element analysis (FEA). The stent-patterned airway scaffolds with a removable central core to preserve an internal lumen were created by selective laser sintering (SLS) based 3D printing. The stent-patterned airway scaffold with the central core, filled with poly (ethylene glycol) diacrylate-dithiothreitol (PEGDA-DTT) hydrogel containing erythropoietin (EPO) to enhance vascularization, was then implanted into the latissimus dorsi muscle of a Yucatan minipig.

Results: A tubular tissue flap, with controlled luminal layer thickness was successfully created by removing the central core from the retrieved tissue flap containing the airway scaffold after 45 days of implantation in the Yucatan minipig model.

Conclusion: The current work validated the potential of the tubular tissue flap based on the 3D printing as a clinically viable tissue engineering strategy for long segment tracheal reconstruction.

Keywords: 3D printing; Flap reconstruction; Selective laser sintering; Tracheal reconstruction; Vascularization.

Fig. 1

Schematics of 3D printing based tubular tissue flap strategy for long segment tracheal reconstruction. A Implantation of the airway scaffold including the central core (white color) and PEGDA-DTT hydrogel containing EPO (yellow color) into the latissimus dorsi muscle of a Yucatan minipig, B Retrieval of cylindrical tissue flap composed of the airway scaffold and regenerated tissues, C Incision of both ends of the regenerated tissues surrounding the airway scaffold, D Removal of the central core from the tissue flap. E Implantation of the tubular tissue flap into the segment tracheal defect

Fig. 2

Design of the airway scaffolds. A Airway scaffold without stent-pattern, B Airway scaffold with a stent-pattern, C Airway scaffold with two stent-patterns, D The stent-patterned airway scaffold with the hollow porous central core to create the tubular tissue flap in vivo

Fig. 3

The top view of the airway scaffold infilled with PEGDA hydrogel containing EPO A before and B after the central core lid assembly, C The latissimus dorsi musculature embedding the airway scaffold infilled with PEGDA hydrogel containing EPO

Fig. 4

Mechanical behavior analysis of airway scaffolds according to the stent-pattern application. The load and displacement curves of airway scaffolds under A parallel compression, B perpendicular compression, C parallel three-point bending, and D perpendicular three-point bending

Fig. 5

3D Printing and mechanical test results of the airway scaffold with two stent-patterns. A Photographs of the printed airway scaffold with two stent-patterns. The load and displacement curves of airway scaffolds under B parallel compression and C perpendicular compression to the airway scaffold opening (n = 4)

Fig. 6

Cumulative release of EPO from PEGDA hydrogel (n = 3, *p < 0.05 versus day 1)

Fig. 7

Pedicled latissimus dorsi tubular tissue flap after 45 days of implantation. A Incision of the muscle tissue flap with the embedded airway scaffold, B Central core removal from the tissue flap, C The tubular tissue flap based on the airway scaffold after removal of the central core

Fig. 8

Evaluation of tissue formation surrounding the airway scaffold. A H&E and B MT staining results of longitudinal cross-section of the regenerated tubular tissue flap based on the airway scaffold at 45 days after implantation. Scale bar, 2 mm. White arrows indicate the blood vessels in the regenerated luminal tissue