Novel Zinc-Nanocomposite Materials for Pediatric Bioresorbable Cardiovascular Stents

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ABSTRACT Many infants with congenital heart disease are born with obstruction in the aorta (aortic coarctation) or in the pulmonary arteries. Options for adults with these severe vascular obstructions include medications, surgery, and catheter-based interventions such as stents. For pediatric patients that do not respond to medications, surgery posts increased risks, and stents are not recommended because growing children require stents that either grow with the child, or biodegrade after tissue remodeling, so that the developing tissues can grow with the rest of the body. Unfortunately, most bioresorbable stents (BRS) in the pipeline are polymer stents designed for coronary arteries. As such, these stents are too soft to handle aortic and pulmonary pressures, and too small. Bioabsorbable metals are an attractive alternative for BRS. Metals have a higher mechanical strength and toughness than polymers, and many have a proven history of biocompatibility in vivo. One such metal is zinc. As an essential element in basic biological functions, zinc is well tolerated by living tissues, and recent in vivo studies have demonstrated that zinc has a steady corrosion rate with no severe adverse events. Furthermore, zinc has greater elongation to failure than other commonly studied metals for stents – important for expandable stent deployment. These properties make zinc an excellent candidate for pediatric BRS. However, pure zinc is mechanically weak, and requires alloying to the increase its strength. Unfortunately, this often comes at the cost of other favorable properties, such as corrosion rate, ductility, and/or biocompatibility. Recently, reinforcing metallic materials with nanoparticles has demonstrated great potential as a strategy to significantly enhance mechanical properties. By using nanoparticle-dispersions, zinc’s mechanical properties can be improved significantly while retaining the favorable properties of zinc. Therefore, our hypothesis is that zinc-nanocomposites can be used to manufacture BRS suitable for pediatric applications that maintain sufficient structural integrity for 4-6 months before completely degrading into non-toxic byproducts. The development of a pediatric BRS fabricated using zinc-nanocomposite for the treatment of congenital heart disease will be achieved by pursuing the following aims: Aim 1 – Optimize zinc and nanoparticle combination to strengthen zinc-nanocomposite materials for manufacturing of functional pediatric BRS. Aim 2 – Characterize the biocompatibility, and mechanical properties of zinc- nanocomposites in vitro. Aim 3 – Assess in vivo efficacy and biocompatibility of zinc-nanocomposite stents in a rapidly growing pig animal model. The anticipated results will provide much needed guidance to further fine tune the core materials. Ultimately, a mechanically robust, biocompatible, and biodegradable stent has the potential to revolutionize the treatment of arterial obstructions in pediatrics patients by eliminating the need for open chest surgeries in infants and older children. Additionally, the knowledge gained from this research will have a broad impact on the development of safe and efficacious bioabsorbable metallic implants for many clinical applications.