In situ formation of micro/nano phase composite for 3D printing clinically relevant bioresorbable stents

Abstract

With recent developments in materials engineering and additive manufacturing, the feasibility of patient-specific biomedical devices has increased substantially. Bioresorbable vascular stents/scaffolds (BVS), implants which reopen narrowed blood vessels, have seen considerable research in freeform fabrication as one such potentially customizable medical device. However, clinical requirements for stents place significant limits on manufacturing; the device must maintain the vessel's natural diameter once it has been reopened and must have sub-100 μm radial thickness to allow proper blood flow in small diameter vessels. Recent commercialization challenges for BVSs have highlighted the importance of meeting these requirements. For example, the first BVS marketed in the U.S.A., made from polylactide, had a radial thickness of 150 μm, which potentially contributed to negative side-effects and reduced efficacy. Thus, new bioresorbable materials and manufacturing strategies are required to fabricate BVSs that have sub-100 μm feature sizes that are mechanically competent and safe. In this work, we report the innovative use of a two-phase system that enables in situ formation of semicrystalline poly-l-lactic acid nanofibrous networks within a 3D printed polymeric matrix of a bioresorbable citrate-based biomaterial used for the first time in a resorbable medical device recently approved by the Food and Drug Administration. The optimized composite ink is compatible with the high-resolution micro-continuous liquid interphase production method with demonstrated smallest printable features of 80 μm. The resulting composite material has a significantly improved Young's modulus of 969.55 MPa at the fully hydrated state, a 108% improvement over the previously reported pure citrate-based biomaterial materials. We have successfully fabricated the BVS with strut thicknesses less than 100 μm and demonstrated that the stent can sustain applied vessel loading under physiological blood pressure conditions. The fabrication method can potentially be broadly applied to other biomedical devices.