Controlling the alignment and degradation of 3D printed poly-L-lactic acid for redesigned coronary stents

Abstract

Cardiac stents are used for treating heart disease, widening the blocked artery to restore normal blood flow. However, most stents are permanent. This posits several problems, including the long-term risk of restenosis and thrombosis. Consequently, significant research is focused on creating biodegradable stents. The most commercially successful material for this is polylactic acid (PLA), although, numerous challenges remain before the stent’s wider implantation. As a material, PLA is widely used within fused filament fabrication (FFF) 3D printing. FFF could be a viable technique for manufacturing patient-specific cardiac stents. Furthermore, the ideal strut thicknesses, no greater than 100 µm, are readily achievable using FFF. However, achieving the required radial stiffness at this size remains a challenge within 3D printed PLA. This thesis explored methods to improve the polymer chain alignment and resultant Young’s modulus of 3D printed single-layer poly-L-lactic acid (PLLA). Results showed that polymer chain alignment can be increased by raising the bed temperature, lowering the nozzle temperature or increasing nozzle diameter, with birefringence increasing from 0.0007 ± 0.0001 to 0.0011 ± 0.0003. In addition, post-printing annealing and sample shearing were explored. By changing the annealing time and temperature, the crystallinity and crystal structure could be controlled. The resultant Young’s modulus increased from 2.00 ± 0.46 GPa to 2.77 ± 0.28 GPa. Sample shearing formed an oriented crystal structure and increased the Young’s modulus to 2.78 ± 0.17 GPa. In a small number of reported cases, implanted commercial PLA stents have suffered from uncontrolled degradation and increased risk of late-stage thrombosis. Internal differences in microstructure, arising from the manufacturing and implantation process, resulted in an asymmetric degradation profile. If, however, the effect of microstructure on degradation rate was better understood, a "safety stent" could be produced, degrading in a controlled sequence in vivo. To understand the effect of initial microstructure on degradation rate, a 6-month degradation study was conducted, involving both initially amorphous (PLLA-A) and semi-crystalline 3D printed PLLA (PLLA-C). 100 µm thick samples were degraded in phosphate-buffered saline at 37 ◦C. Prior to the onset of mass loss, the rate constant for homogenous bulk degradation for PLLA-C was 6.14×10−8 ± 3.85×10−9 days−1 , whilst for PLLA-A it was 7.58×10−8 ± 1.18×10−8 days−1 . The crystalline regions were suggested to restrict the diffusion of fluid into the microstructure, reducing its degradation rate. Accelerated degradation testing at elevated temperatures is often reported for PLLA, offsetting the difficulties involved in long degradation experiments. However, despite its usage, its validity for 3D printed thin (c. 100 µm diameter) samples, where autocatalysis may not play a significant role, needs to be investigated. PLLA-A and PLLA-C were degraded at 50 ◦C and 80 ◦C, with the results compared with degradation at 37 ◦C. Irrespective of the initial microstructure, the results showed that accelerated degradation testing was invalid. At 37 ◦C, the crystallinity did not change. At 50 ◦C and 80 ◦C, the crystallinity increased, altering the progress and kinetics of the degradation. The degradation medium acted as a plasticiser reducing the glass transition temperature of PLLA, enabling crystallisation at these elevated temperatures. It was concluded that accelerated degradation should not be undertaken for PLLA samples with thicknesses relevant to stent applications. Commercial stent designs are not optimised for FFF 3D printing. Limited inter-diffusion within 3D printed material is known to reduce joint strength. One solution is to remove all joints from the design. Jointless stents, based on Peano curves folded into three dimensions, were explored. In collaboration with a cardiologist, several designs were 3D printed onto a rotating mandrel. Finite Element Analysis (FEA) was used to simulate the implantation process of the most promising design. The recorded central recoil (3.6 ± 1.3 %) was of comparable magnitude to commercial stents. Furthermore, a variable property stent, with different mechanical properties in different regions, was simulated. By controlling the polymer microstructure and subsequent mechanical properties in specific regions, the spatial distribution of plastic deformation could be changed, as well as the unwanted central recoil from a jointless cardiac stent reduced. This thesis researched several hurdles to overcome before biodegradable PLLA stents can be widely used. The promising results could inform future stent design, producing new implants with a better long-term outlook for patients.