Bioresorbable Vascular Scaffolds Gain Ductility, Resistance to Hydrolysis, and Radial Strength via a Unique Poly L-lactide Microstructure

Citation

Ramachandran, Karthik (2019) Bioresorbable Vascular Scaffolds Gain Ductility, Resistance to Hydrolysis, and Radial Strength via a Unique Poly L-lactide Microstructure. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/9146-5159. https://resolver.caltech.edu/CaltechTHESIS:11162018-140640407

Abstract

Advances in tissue engineering over the past few decades are poised to revolutionize drug delivery and biomedical implants. Bioresorbable vascular scaffolds (BVS), which are made from the semicrystalline polymer poly (L-lactide), are an example of polymers saving and improving the quality of human life. BVSs are emerging as a promising alternative to metal stents for the treatment of coronary heart disease (CHD), one of the leading causes of death in the world. In contrast to permanent stents, BVSs are designed to have a limited lifespan in the body; they restore blood flow through the occluded artery by lending it support for 3-6 months, but are completely resorbed in 2-3 years, leaving behind a healthy artery. This transient character of BVS restores vasomotion in the treated artery and can eliminate the risk of thrombosis, a dreaded complication regarded as the bane of stenting.

The promising success of the first and currently only clinically-approved BVS (FDA-approval in 2016) provides an impetus to continue its development. The struts of the BVS (~ 150μm) are nearly two times thicker than in metal stents (~ 80μm). A thicker device is challenging to implant and is unable to treat smaller and tortuous arteries. Furthermore, clinicians speculate that irregular blow flow over thicker struts may contribute towards thrombosis. An added complication of working with BVSs is that they are difficult to visualize with X-rays owing to the low atomic mass of polymers. The need for a BVS that is thinner, stronger, and radio-opaque is the motivation for this thesis, which aims to extend the benefits of transient implants to a broader patient population. Chapter I provides a brief chronological overview of the evolution of cardiovascular therapeutics to combat CHD. Chapters II and III elucidate micron-scale gradients in the PLLA microstructure of the clinically-approved BVS that overcome PLLA’s inherent brittleness and provide lasting radial support to the artery. Chapter IV discusses the fabrication of novel instrumentation to establish structure-property relationships for scaffolds, and Chapter V explores polylactide nanocomposites that not only increase radial strength in a thinner profile but also provide radio-opacity.

Thesis Files