4D Printing of Porous Scaffolds for Vascular Tissue Engineering

Abstract

3D printing has enabled us to fabricate hollow structures for vascular tissue engineering. Currently, there are mainly three 3D printing approaches to make hollow structures, mimicking vasculature: indirect printing through a sacrificial core, direct printing of interconnected channels structures, direct printing of tubular structures using a coaxial nozzle. But these approaches have difficulties in fabricating hollow porous tubes with accurate control over their diameters and architectures. 4D printing has emerged recently for producing structures which can change their shapes under external stimuli. It has great potential to create dynamic structures for tissue engineering. For promoting vascular tissue regeneration, vascular endothelial growth factor (VEGF) is often encapsulated in tissue engineering scaffolds. In this study, 4D printing was used to create shape morphing porous scaffolds, which could change from planar shape to small diameter tubes, for vascular tissue engineering. Poly(D,L-lactide-co-trimethylene carbonate) (PDLLA-TMC), a polymer which changes shape upon heating to a temperature above 37°C, was used to make scaffolds and gelatin methacryloyl (GelMA) was the functional layer on scaffolds for VEGF loading. PDLLA-TMC was firstly printed to form planar porous structures. They were then shaped into tubular porous structures using a glass stick as a template at 80°C, thereby defining the permanent shape of PDLLA-TMC porous structures. The tubes were flattened at room temperature and VEGF-loaded GelMA hydrogel was printed onto them, followed by UV photo-crosslinking. The PDLLA-TMC/GelMA planar porous scaffolds could be self-rolled into tubular porous scaffolds at 37°C. In vitro VEGF release for 4D printed scaffolds was studied, and steady and sustained release was observed. Endothelial cells were seeded onto scaffolds whose biocompatibility was assessed using LIVE/DEAD assay. Results showed good cell viability after 3-day culture. MTT assay results suggested good cell proliferation after 1, 2, 3-day culture.