Tunable Platform for Drug Eluting Stents

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality claiming 610,000 lives and 200 billion dollars annually in the United States. Driven by atherosclerosis, CAD manifests as thickening and stiffening of the arterial walls due to plaque buildup. To recover normal blood flow, stents emerged as a pivotal instrument to reopen constricted arteries. While revolutionary at the time of discovery, there are significant issues that are still present. Specifically, there are four common complications: restenosis, infection, thrombus, and inflammation. To mitigate these, drug-eluting stents (DES) were developed, adding a coating loaded with anti-proliferating drugs to deliver locally. Despite the advantages of DES, clinical complications continued. Primarily, low drug loading capacity, poor temporal tunability, and sub-optimal compatibility of the polymer-coating lead to late-stage thrombosis and low reendothelialization. <b>Given this, there is an urgent need for a DES that provides a programmable passive drug release while minimizing adverse effects. </b><br/><br/>Here, we removed the less-biocompatible coating altogether, instead, adding a slippery liquid-infused porous surface (SLIPS) – a novel biocompatible coating – where the drug can reside in the matrix of the sintered nanoparticles or the lubricant, specifically termed infused DES (iDES). This design results in decreased foreign body response (FBR) due to the anti-biofouling effects of SLIPS and increased drug loading with bimodal release capacities tuned through the tailoring of chemistries. <b>Unique to iDES, the platform design offers three independently tunable parameters – stent material, coating properties, and drug delivery kinetics – creating a solution that can be precisely tailored to each patient.</b> The stent material, Nitinol, is commonly used in implants, as it is a super elastic metal that can withstand high intrinsic strain. The mechanical tunability comes from the geometry of the design such as pitch, width, and thickness. Moreover, the design imparts the base stent regions of stress-prone and stress-free drug-loadable islands capable of varied kinetics under blood flow’s fluid shear forces depending on the specific geometry chosen. The coating comes from the SLIPS technology, an anti-biofouling surface that significantly reduces infection risk. The tunability comes from the option to load the drug in the nanoparticle’s matrix or the lubricant, with varying release and customization for both. The lubricant offers a faster release, with the phobicity and viscosity affecting the kinetics. Due to the longer diffusion, loading the drug into the matrix gives a slower release with the nanoparticles’ size, functionalization, and porosity determining the kinetics. The ability to load drugs into two matrices allows for a patient-targeted approach, without the concern for poor biocompatibility. In tailoring medical devices to individual patients, kinetics and drug selection adaptability become essential, allowing for personalized adjustments that align with a patient's physiological and therapeutic needs. iDES aims to be the next generation of medical devices that can be catered for each patient’s needs minimizing revision surgeries and unnecessary visits.