3D-Printing of Mechanically Competent, Low Profile, Radiopaque Bioresorbable Vascular Scaffolds

Atherosclerotic artery diseases, caused by the narrowing or clogging of arteries from plaque build-up, are responsible for significant morbidity and mortality rates worldwide. The placement of a metallic stent with or without coating of drugs following angioplasty is widely used to re-open the artery blockage and restore the blood flow. However, the permanent presence of such metallic stents hampers normal vasomotion, limits adaptive arterial remodeling, and can provoke long-term foreign-body responses. To address these issues, polymeric bioresorbable vascular scaffolds (BVSs) have emerged by providing temporal mechanical support (i.e. scaffolding), degrading over time to eliminate foreign materials, and eventually disappearing while vessel functions are restored. Yet current BVS, such as Abbott’s Absorb have not shown better outcomes than drug-eluting metallic stents due to disadvantages of currently used polymeric materials, such as poly(l-lactic acid) (PLLA). The material drawbacks include: 1) oxidative tissue damage and exacerbated inflammation as induced by their degradation products; 2) their inferior mechanical properties necessitate a larger BVS profile (~150 μm strut thickness), leading to larger disturbance of blood flow and higher incidence of thrombosis; and 3) a lack of radiopacity and the resulting poor tracking ability under X-ray during the BVS deployment may increase the rates of stent malposition. In addition, the traditional manufacturing method of BVS, e.g. laser machining does not allow for patient-specific customization, which could improve vessel patency. Although the recent application of 3D printing in BVS fabrication offers more flexibility for scaffold customization, they are still limited by their resolution, speed, and selection of printable materials.<br/> To address these issues, we have developed photocurable citrate-based bioresorbable polymer inks and a 3D printing technique referred as micro continuous liquid interface production (μCLIP) to produce BVS. We demonstrated that the use of citrate-based polymer, which was recently approved by FDA, offered excellent biocompatibility and antioxidant properties to the 3D-printed BVS. The mechanical properties of citrate-based polymer were further reinforced by the incorporation of PLLA nanofibrous network. Young’s modulus of a hydrated composite was 1.3 GPa, which is 2.8-fold increase compared to the pristine polymer. Moreover, the mechanical reinforcement in combination with high-resolution μCLIP process (7 μm precision) led to the successful production of low profile BVS with strut thickness less than 100 μm, which is 50% thinner than Absorb GT1 scaffold (Abbott Vascular), while sustaining physiologically relevant vessel loading. In addition, the strong radiopacity of the BVS was achieved through two methods: 1) the attachment of biodegradable radiopaque markers (i.e. molybdenum) at two ends of BVS to aid accurate placement, and 2) the incorporation of a clinically-used X-ray contrast agent, i.e. iodixanol (Visipaque) into the polymer ink to provide radiological visibility of the entire BVS. Finally, we successfully deployed and tested our 3D-printed BVS in rabbit iliac artery stenting model. The <i>in vivo</i> results suggested that our 3D-printed BVS showed a good biocompatibility and vessel patency without thrombosis. Overall, this study presents a new material and manufacturing platform to produce mechanically competent, low profile, and radiopaque BVS. The reported innovative strategies can be broadly applied to other medical devices.