Next-generation bioresorbable vascular scaffolds offer an alternative to metallic drug-eluting stents.
By James M. Lindsey III, Zeus
Once hailed as the fourth revolution in percutaneous coronary intervention (PCI), bioresorbable vascular scaffolds (BRS) did not live up to the hype. Leveraging the fundamentals of PCI innovations that came before it — balloon angioplasty, bare-metal stents, and drug-eluting stents (DES) — the idea of a magical device that could provide the same era-defining functionalities and then disappear was an exciting proposition.
While promising, first-generation polymeric BRS suffered from several fundamental limitations. Due to the relatively lower strength of the Poly-L-lactic acid (PLLA) polymer, the scaffold struts were required to be thicker at ~150 microns versus ~80 microns for DES, creating a more thrombogenic environment due to disturbances in blood flow. Also, due to the limitations in the polymer’s ductility, limited over-expansion ratios were prescribed, providing less room for error during sizing and implantation, thereby increasing the likelihood of strut-malapposition and subsequent intraluminal scaffold dismantling upon scaffold degradation.
However, even with these drawbacks, it has been reported that while adverse events were more common with the first-generation scaffold than with a contemporary DES, the period of excess risk ended at three years, corresponding to the time for complete scaffold resorption. Therefore, if comparable safety and efficacy to that of DES can be achieved during the first three years post-implantation, BRS technology may indeed live up to its potential, and not only in the treatment of coronary artery disease (CAD), but also in the treatment of peripheral artery disease (PAD).
Stringent requirements: a challenge for effective polymeric BRS
A BRS has a dual mandate: Provide safe and effective arterial/radial support to prevent post-revascularization recoil; and resorb in a benign fashion, allowing for the restoration of the natural vessel function.
For a polymeric BRS, providing effective radial support is no small task. BRS are required to have a low delivery profile, requiring them to be both crimpable and expandable, resulting in a high degree of localized strain. On top of that, it is often required that a BRS be “over-expanded” to achieve good strut apposition to the vessel wall. After this high-strain-laden implantation process, the BRS must be able to maintain a high yield stress to prevent vessel recoil.
Finally, after providing sufficient support for vessel remodeling, the BRS must resorb without complication. How can a BRS possibly meet these stringent requirements? The answer lies in optimized polymer microstructure.
Polymer microstructure: the key to new beginnings
BRS are most commonly fabricated by laser cutting a polymeric precursor tube. As such, the chemical and mechanical properties of this precursor tube are paramount in achieving a safe and effective BRS. The selection of an appropriate polymer chemistry sets the stage for not only the duration of luminal support, load transfer, and time-to-complete absorption, but most importantly, provides the chemical template for the control of polymer microstructure. Polymer microstructure is defined primarily by the spatial positioning of polymer crystallinity and molecular chain alignment. It is critical that all steps in the manufacturing process of a BRS be designed with an eye toward optimal polymer microstructure, and not only an optimal microstructure at the time of implantation but also throughout the various phases of degradation and resorption.
For a BRS to undergo high strain without failure, a highly aligned microstructure, often referred to as high molecular orientation, coupled with small-crystallite crystallinity, is required. This microstructure transforms the polymer from one susceptible to brittle fracture to one with high strength and ductility. In addition, highly uniform spatial positioning of such microstructure allows for predictable and uniform degradation, taking aim at two of the major late outcome drawbacks of first-generation BRS, namely intraluminal scaffold dismantling and thrombosis.
Tailored microstructure for tailored BRS designs
BRS for the treatment of both CAD and PAD can differ considerably in design, sizing, and functionality. Because of these differences, a polymer tube comprised of a single microstructure is not likely to be an ideal precursor for multiple BRS designs.
New advancements in polymer processing techniques enable tailored microstructures for tailored BRS designs. Through the application of multi-dimensional stresses governed by precise control over strain, strain rates, and temperatures, these new techniques allow for precise control over polymer crystallinity, crystallite size, and molecular orientation across multiple axes of the precursor tubing.
The application of these stresses in a three-dimensionally uniform fashion provides critical levels of uniformity, including dimensional uniformity, mechanical property uniformity, and uniformity of degradation, all leading to consistent and predictable BRS performance in the acute phase and throughout resorption and vessel restoration.
Given that a BRS design laser-cut from a precursor tube will assume the three-dimensional microstructure of the tube by superimposition, the ability to tailor the three-dimensional tubing microstructure for a particular BRS design is paramount in achieving an optimized result. Molecular orientation can be tailored bi-axially to yield circumferential and longitudinal orientation profiles that favor specific BRS designs with respect to functionality and specific stress-strain responses experienced during crimping and deployment. This customization allows for the precursor tubing to be tailored to specific BRS designs, and for unique BRS designs with differentiating features to be realized.
Paving the way for the future
New polymer processing techniques capable of precisely controlling the polymer microstructure are enabling novel BRS designs for the treatment of both CAD and PAD.
Tailored microstructures now allow for thin-strut BRS designs with high radial strength and improved over-expansion capabilities for coronary and BTK BRS as well as high-strength, large-diameter designs for ATK BRS. Advancements in tailored and highly uniform microstructure provide a platform for uniform degradation and improved clinical outcomes, while newly offered polymer chemistries beyond PLLA, such as PLGA (poly-L-lactide-co-glycolide) and PLC (poly-L-lactide-co-caprolactone), are allowing for even greater possibilities with respect to resorption time and BRS functionality, including self-expanding BRS.
Armed with these new techniques and capabilities, new BRS therapies that once seemed unimaginable are now within reach.
James M. Lindsey III is a senior research engineer at Zeus with Bachelor of Science degrees in Biological Sciences and Mechanical Engineering, and a Master of Science degree in Bioengineering, all from Clemson University. Lindsey played a leading role in the invention of Absorv XSE, Zeus’ flagship bioabsorbable oriented tubing platform designed for next-generation BRS, as well as many other bioabsorbable products.
How to submit a contribution to MDO
The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design & Outsourcing or its employees.
