219Three-dimensional printing as a cutting-edge, versatile and personalizable vascular stent manufacturing procedure: Toward tailor-made medical devices

Abstract

Vascular stents (VS) have revolutionized the treatment of cardiovascular diseases, as evidenced by the fact that the implantation of VS in coronary artery disease (CAD) patients has become a routine, easily approachable surgical intervention for the treatment of stenosed blood vessels. Despite the evolution of VS throughout the years, more efficient approaches are still required to address the medical and scientific challenges, especially when it comes to peripheral artery disease (PAD). In this regard, three-dimensional (3D) printing is envisaged as a promising alternative to upgrade VS by optimizing the shape, dimensions and stent backbone (crucial for optimal mechanical properties), making them customizable for each patient and each stenosed lesion. Moreover, the combination of 3D printing with other methods could also upgrade the final device. This review focuses on the most recent studies using 3D printing techniques to produce VS, both by itself and in combination with other techniques. The final aim is to provide an overview of the possibilities and limitations of 3D printing in the manufacturing of VS. Furthermore, the current situation of CAD and PAD pathologies is also addressed, thus highlighting the main weaknesses of the already existing VS and identifying research gaps, possible market niches and future directions.

Keywords: Atherosclerosis; Coronary artery disease; Endovascular prosthesis; Peripheral artery disease; Stent; Three-dimensional printing.

Figure 1.. (A) Economic burden caused by CAD and PAD in France, Germany, and Canada. Left: average cumulative 1-year and 2-year direct medical costs associated with hospitalization/patient for both CAD and PAD (H stands for “hospitalization”). Extracted from Smolderen et al.^[145] Right: Average hospitalization and annual medication costs per patient in Canada. Extracted from Bauersachs et al.^[5]. Bars numbers correspond to amount in euros. (B) Global vascular stents market share by product type. EVAR stands for “endovascular aortic repair.” Values extracted from^[9].

Figure 2.. (A) Classification of VS based on their degradability, type of blood vessel (to treat CAD or PAD) and implantation methodology. (B) Relative amount of VS commercially available in the market. BRS stands for “bioresorbable stents,” SS “stainless steel,” SE “self-expandable stent,” and DES “drug-eluting stent.” The sector graph is drawn according to the information available in Table 1.

Figure 3.. Schematic representation of VS implantation procedures. Top: balloon-mediated stent delivery; bottom: self-expanding stent delivery.

Figure 4.. 3D printing techniques classified based on their additive manufacturing mechanism (ISO/ASTM 59000:2021).

Figure 5.. Combination of PLA and PVA for the production of VS by means of FDM 3DP. PVA was included as a sacrificial material allowing the printing of a self-standing structure. After the printing process, PVA was dissolved and eliminated, revealing the final VS structure, which is made of PLA. The influence of stent diameter, wall thickness and geometric parameters of the auxetic structure were studied, and different printed VS and their mechanical properties were evaluated. Graphics included in the figure correspond to radial force (per unit length) versus radial displacement curves for each stent. Reproduced with permission from [62] 2018, Materials.

Figure 6.. (A) Tilted structures printed (scale bar: 1 cm). (B) Steps of in vitro deployment testing. Different frames, from (a) to (d), show the shape memory effect of PGDA after photocrosslinking and thermal curing. Effective deployment inside a compressed silicone tube. (C) Results of in vivo studies in mouse aorta; (a) images after implantation and (b) after 14 days; (c), (d), (e), and (f) correspond to different staining techniques of middle/inner (c and e) and outer layers (d and f) of newly formed tissue after 14 days of VS implantation. Black arrows indicate inner elastin layer and green arrows indicate outer elastin layer; (g) endothelial cells stained with VE-cadherin antibody (green) and cell nuclei stained with DAPI (blue); (h) myofibroblasts (red) and nuclei stained with DAPI (blue). Reproduced with permission from [64] 2021, Acta Biomaterialia.

Figure 7.. (A) Pulling platform for deposition process over the sacrificial mold obtained by means of 3DP. (B) Shaped nitinol wires to be used in the final stent. (C) Final aspect of aortic metal-PU stents with different shapes (branched and straight). Reproduced with permission from [68] 2020, Medical Engineering and Physics.

Figure 8.. (A) Scanning electron microscopy of printed PLA stents: (a) full PLA stent; (b) entire surface image; (c) exterior connection; (d) interior connection. (B) Confocal laser scanning microscopy (CLSM) of smooth muscle cells (SMC, red) and endothelial cells (EC, green) seeded over the produced stents. PLA stands for pure PLA stents; PLADP stands for PLA stents after PEI immobilization; PLADPH refers to stents loaded with heparin after surface modification. Bar charts represent the percentage of cellular proliferation (both SMC and EC) at day 1 and day 3, thus demonstrating significant differences between samples. Reproduced with permission from [14] 2019, Chemical Engineering.

Figure 9.. (A) Photographs and scanning electron microscopy of mDPC-SNAP stent. (B) Schematic representation of the DLP printer used. (C) Stress– strain compression curves for uncured and post-cured mPDC stents at different times and with different diameters (a and b). Photographs frames of a stent of 6 mm diameter during stress–strain compression test (c–e). Reproduced with permission from [75] 2021, Bioprinting.

Figure 10.. (A) Digital stent prototype optimized for PBF 3DP. (B) Scanning electron microscopy images of printed VS after electrochemical polishing; images at the upper panel belong to VS produced by hatching PBF scanning, whereas images at the lower panel correspond to a stent produced with concentric scanning PBF. (C) Scanning electron microscopy images of 3DP CoCr VS produced by hatching (top) or concentric strategy laser scanning (bottom) and their differences. Laser pulse duration is indicated in each case. Reproduced with permission from [37] 2019, Materials & Design.

Figure 11.. (A) Schematic representation of stent parts and nomenclature. (B) Geometrical design of commercial NIRxcell stent, which possesses different strut widths within the same structure. (C) Some examples of strut connections. (D) Non-uniform Poisson’s ratio stent 2D structure. Reproduced with permission from [82] 2021, Micromachines.

Figure 12.. Design and real aspect of bifurcated self-expandable stent produced by FMD using a shape memory polymer. The bifurcated branch is able to deform until the formation of a single conduit, thereby allowing implantation. The suitability of this VS for deployment in a bifurcated vessel was tested in a silicon, transparent mold. Scale bars: 20 mm. Reproduced with permission from [66] 2018, Scientific Reports.