3D printing of stents via two-photon polymerization

Abstract

Stents are medical devices used to treat the narrowing of the blood vessel, most commonly caused by atherosclerosis. Currently used bare-metal, drug-eluting stents are limited in size and architectural complexity, and there are a few risks associated with these medical devices. In some cases stents can cause thrombosis or even death. Furthermore, said risk increases while stenting relatively small vessels. This paper shows that vascular stents for relatively small vessels and/or for patient-specific stenting applications can be printed using two-photon polymerization (2PP). 2PP is an additive manufacturing technique with sub-μm resolution and unlimited 3D geometry potential. These capabilities were used to produce stents for small blood vessels, which are 5 mm tall and 0.7 or 0.9 mm in diameter, with 3D struts as thin as 50 μm. Several novel approaches were introduced to accommodate the printing of such a structure like voxel elongation and printing in stereolithography-like vat-sample holder configuration. Furthermore, the produced stents were tested mechanically proving their mechanical resilience to most common types of mechanical deformations. Experimental results were also compared to mathematical modeling, showing excellent agreement, hinting at the possibility of designing and testing complex micro-stent geometries before fabrication in silico. Finally, biocompatibility experiments were performed, in which rats survived the 7-day incubation period and showed no significant biocompatibility issues. Overall, the presented work gives an outlook on all aspects related to the 3D printing of stents - design, manufacturing, mechanical, and biological testing. We show that 2PP aligns very well with all these aspects and is a promising technique for the mass manufacturing of vascular stents for small vessels or specifically for the patient.

Figure 1

The schematics present the study workflow. First, CAD models of stents were generated. The printing process followed, with the goal of preparing structures for mechanical and biological testing. Additionally, cylinder samples were prepared from the same material as the stents. Mechanical testing was performed in two steps - experimental material characterization and in silico modeling. Finally, stents were validated using rats in vivo.

Figure 2

Schematics of application of elongated voxels for high throughput stent manufacturing. (a) and (b) shows the progression of the process. Expansion of voxel to the width of 10  allows to reduce the number of translations needed to manufacture a single layer. At the same time, a regular hatching and slicing algorithm is applied, and the structure is printed in a layer-by-layer fashion. Therefore, printing is exceptionally fast but realized in a fundamentally straightforward fashion.

Figure 3

Stents of various sizes. (a) - from left to right, the image shows vascular stents printed using voxel elongation technology, with heights of 50 mm, 10 mm, and 5 mm, (b) - 0.7 mm diameter stent SEM micrograph, (c) - 0.7 mm diameter stent SEM micrograph visualizing the 50  m strut thickness.

Figure 4

Tests to evaluate samples visually. Still images taken out of the video observe mechanical manipulation of a 3D printed 5 mm tall stent. Bending, crushing, and pulling were attempted using either plastic probes or metal tweezers. Although all tests were performed in sequence and mechanical defects, such as cracks, could accumulate, however, stent still maintained its structural integrity. Subsequent tests with other stents showed the result to be highly repeatable.

Figure 5

Numerical experiment results for specimen compression and experimental and numerical results comparison.: (a) specimen photo, (b) Strain vs. compression force curve for a cylindrical specimen, (c) Experimental and numerical results comparison, (d) Results of the numerical experiment.

Figure 6

The second experimental phase of numerical testing. (a) - compression test, (b) - tension test, (c) - bending test, (d) - local compression test, (e) - computational-fluid dynamic model of blood structure, (f) - maximum blood velocity in the center of a vein in the presence of a stent.

Figure 7

Representative photographs of cross-sections of carotid arteries obtained from Wistar lineage rats after a 7-day period. In the control group (a), all major layers are visible, and their relative thickness is within normal bounds. Test groups (b), (c), and (d) exhibit vasculitis, or mild to moderate inflammation. The architecture of the vessel wall is unaffected, but there is a minor infiltration of granulocytes and lymphocytes (b). There is a reduction in the boundaries between the tunica externa and tunica media, as well as a more intense infiltration of immune system cells (c). More intense damage to the integrity of the vessel wall. The endothelial layer is affected (d). The conventional hematoxylin-eosin (H&E) technique was used to stain the sections.

Figure 8

Schematics of 3D printing 2PP setup used in the work.

Figure 9

Schematics of setup used to perform mechanical indentation experiments of 2PP produced 3 mm diameter cylinders.