Development of Biodegradable Polymeric Stents for the Treatment of Cardiovascular Diseases

Abstract

Cardiovascular disease has become the leading cause of death. A vascular stent is an effective means for the treatment of cardiovascular diseases. In recent years, biodegradable polymeric vascular stents have been widely investigated by researchers because of its degradability and clinical application potential for cardiovascular disease treatment. Compared to non-biodegradable stents, these stents are designed to degrade after vascular healing, leaving regenerated healthy arteries. This article reviews and summarizes the recent advanced methods for fabricating biodegradable polymeric stents, including injection molding, weaving, 3D printing, and laser cutting. Besides, the functional modification of biodegradable polymeric stents is also introduced, including visualization, anti-thrombus, endothelialization, and anti-inflammation. In the end, the challenges and future perspectives of biodegradable polymeric stents were discussed.

Keywords: biodegradable polymeric stents; cardiovascular disease; functionalization; manufacturing method.

Figure 1

Current research progress in biodegradable polymeric stents.

Figure 2

Design (a), processing (b), and implantation (c) of braided mechanical self-reinforcing composite stent.

Figure 3

Schematic illustration for the formation and evaluation of a PVA stent. (a) The design and processing of the PVA stent. (b) The biological property evaluation of the PVA stent. (c) The mechanical property evaluation of the PVA stent.

Figure 4

Stepwise process for developing a personalized coronary stent. (a) Cross-section of the artery shown at the surface of the heart, plaque buildup is shown inside the lumen due to various factors, e.g., aging, diet, genetics; (b) a clot-binding probe, i.e., a fibrin-targeted iodinated CT contrast probe is administered to locate the blood clot. At the same time, volumetric CT imaging helps to get an accurate measurement of the blockage; (c) the imaging information is transferred to a computer-aided design (CAD) software to design a personalized stent; (d) a PCL-GR polymer composite is used for fused deposition modeling additive manufacturing technique in a commercial 3D printing machine; (e) the prototyped stent is placed inside the artery; (f) the incorporation of two drugs for sequential release; (g) the healing process is further monitored by CT imaging; (h,i) the polymer gets biodegraded inside a widened artery.

Figure 5

Stents can be printed with high design flexibility and resolution. (a) CAD images of the initial/primary design (base design) and a secondary design (arrowhead design) that were analyzed in this study. (b) Diagram of continuous liquid interface production microstereolithography (microCLIP) with typical projected photomasks of the stent. (c) 3D-printed base design (top) and arrowhead design (bottom) stents. (d) Scanning electron microscopy images of the base design (top) and arrowhead design (bottom).

Figure 6

Ideal features of biodegradable polymeric stents. The features of stents including visualization, inflammatory response, endothelization, platelet adhesion, and vascular remodeling should be considered (red arrow↑ indicates the promotion effect, blue arrow↓ indicates the inhibition effect).

Figure 7

Schematics of MOF-composited polymeric stent: (a) Use of MOF-composited polymeric stent to prevent coagulation and stenosis while providing MRI visibility and biodegradability. (b) Stepwise process for the development of heparin-coated theranostic MOF-reinforced polymeric stents.

Figure 8

Schematic illustration for the preparation and implantation process of the heparinized PCL stent. (a) The process of heparinization modification of the PCL stent. (b) Schematic illustration of 3D printing personalized, anticoagulant, and biodegradable coronary artery stents guided by magnetic resonance angiography (MRA).

Figure 9

Illustration for the preparation and inflammation assessment of the sandwich-like LBL-coated stents (a) The coating that was fabricated with the sandwich-like LBL coating, in which chitosan, EGCG/Cu complex, and heparin was alternatingly assembled (b) Proliferation of macrophages that were incubated with samples for 24 h. The expression of TNF-α (c), IL-6 (d), and IL-1 (e). Statistical significance was evaluated using a one-way analysis of variance (ANOVA), ** p < 0.01, *** p < 0.001.