Fabrication of Polymeric Small Caliber Artery Grafts Using 3D Printed-assisted Prototyping

Tissue engineering is a multi-disciplinary field aiming to create functional biocompatible constructs that mimic the architecture of the native tissue, to heal or replace injured or missing organs, or fabricating in vitro models for research purposes. Small diameter arteries (<3 mm luminal diameter) affected by cardiovascular diseases might lose functionality, resulting in abnormal blood perfusion, which increases the risk of tissue infarction. Occluded vessels can be replaced or bypassed by engineered perfusable implants. Current techniques for artery graft fabrication rely on approaches that mainly favor larger cylindrical structure fabrication, ignoring the complexity of the native tissue architecture. In this work, we propose 3D printing water-soluble casting molds that can produce intricate hollow grafts. These molds are filled with a biocompatible polymer solution and subsequently freeze-dried, producing a porous scaffold within the cast. The mold is washed away, and the obtained scaffolds are seeded with endothelial cells (EC) or ECs and smooth muscle cells (SMC) combined, further mimicking the native tissue.

MicroCT images show the architecture fidelity of the resulting scaffolds in respect to the fabricated mold regardless of its complexity. Furthermore, polymeric scaffolds present high wall porosity, a key aspect for the in vitro nourishment of seeded cells. After performing a protein coating on the scaffolds, SMC proliferate rapidly, populating the totality of the scaffold, while intralluminaly seeded ECs organize in a cell lining manner. In conclusion, these results show a great potential for the creation of personalized vascular grafts with the capability of mimicking complex architectures.