How the DynamX™ Bioadaptor Works
The development of the next evolution of coronary artery treatment
John Yan, Co-Founder and Chief Technical Officer of Elixir Medical, talks about how the DynamX™ Coronary Bioadaptor System was developed, and the way its unique uncaging elements work to enhance vessel needs and potentially improve patient outcomes.
How did the concept of the DynamX Bioadaptor come about?
We recognized that an improvement upon drug-eluting stents was needed. The very high adverse cardiac events that accrue over time are a problem for both physicians and patients. When 40-50% of patients have significant adverse events at 10 years, it’s clear that something better is needed. What may be causing this problem is that rigid metallic stents “cage” the artery. This prevents the artery from exhibiting its natural response to expand and compensate for disease progression, and does not allow it to respond to the body’s changing blood flow needs. This phenomenon of “caging” of natural coronary artery movement has been associated with MACE (major adverse cardiac events).
The industry responded to this challenge with bioresorbable scaffolds, or BRS. The idea was to develop a stent that could support the vessel and then enable it to move naturally in response to the body’s needs once it has resorbed. There was a lot of promise with this idea and a lot of enthusiasm in the interventional cardiology community, including from many physicians. A number of companies developed BRS devices, including Elixir Medical. BRS devices had benefits but also challenges. They successfully resorbed over time and restored artery functionality, but required a change in the standard implantation technique. Some BRS products took a long time to resorb and had late clinical event rates, particularly late thrombosis. Although Elixir’s BRS, DESolve, was unique in having early resorption and excellent clinical data, the acute performance did remain a challenge. As a result of the changes required for implantation and the adverse clinical event rates, BRS therapy ultimately did not succeed.
However, we gained a great deal of understanding from our BRS experience about the importance of implantation technique, material performance and that restoration of the vessel could be achieved. Because of this, we continued to believe in the concepts of restoring artery function and positive adaptive remodeling (the ability to expand and compensate for disease progression) as ways to address long-term adverse events with DES. We were committed to finding a solution. The DynamX Bioadaptor was designed with this experience and knowledge in mind.
We came up with this idea – what if we made a metal implant that can “uncage,” move and expand? We would then have the best of both worlds – a metal stent-like device that deploys easily, has high strength initially and holds open the artery, then after the vessel heals, it can allow the vessel to move (pulsatility and cyclical strain) and remodel (positive adaptive remodeling), restoring vessel function. That was the birth of the bioadaptor.
Explain the unique bioadaptor design and how the “uncaging elements” work.
The idea was to create predictable disengagement, if you will, but also the scaffolding and strength needed during deployment and for the time the artery needs to heal. How do you make both possible?
We developed the idea of incorporating “uncaging elements” into a metal stent-like device. We would coat this device with biocompatible, bioresorbable polymers that would hold these elements together during deployment and acute healing of the artery, and then the coating would dissolve and the device could move with the vessel’s normal movement.
The unique uncaging element design, its positioning along the bioadaptor and numbers of elements per ring were selected after evaluating hundreds of designs in computational modeling, bench studies and preclinical animal studies. The uncaging elements had to provide optimal deployment, scaffolding and radial strength, while allowing the elements to separate after polymer resorption.
The “a-ha” moment for us came in the preclinical study when we saw that histological data, OCT and ultrasound all showed that the inner area of the device and lumen area of the artery increased together. This demonstrated the artery’s natural response of positive adaptive remodeling.
Our subsequent DynamX Mechanistic Clinical Study demonstrated that the “uncaging elements” enable the bioadaptor device to adapt to vessel physiology and accommodate the artery’s dynamic, natural movement. The artery naturally twists, expands and contracts with each heartbeat and dilates in response to the body’s need for blood flow during exercise and disease progression, and the bioadaptor lets the artery behave more as it was intended. By doing this, DynamX may be able to improve upon the current adverse event rate seen in DES.
How is the bioadaptor uncaging action different from programmed strut fracture?
Stent fractures are unintentional breakages in a stent and are caused by metal fatigue in high stress areas in a stent. The fractures are typically asymmetric, traumatic, sharp edges exposing surface areas that are no longer passivated or protected from corrosion (passivation is a process that decreases/eliminates heavy metal ion release and improves corrosion resistance, thereby reducing negative tissue reactions and improving biocompatibility). Stent fractures cause constant irritation in the vessel, leading to increased inflammation, neointimal proliferation and adverse clinical events.
Our “uncaging elements” are purposefully designed to enable motion in sync with resorption of the polymer after vessel healing. They are polished, atraumatic and very smooth. They are symmetrically distributed at low stress areas over each ring and over the entire length of the device. After uncaging, the bioadaptor preserves its smooth, polished, contoured geometry and passivated coating.
The bioadaptor has not shown increased neointima associated with the uncaging elements. OCT shows a uniform thin neointimal coverage along the entire length of the bioadaptor, with over 99% coverage at 12 months. Consequently, the bioadaptor has shown low rates of MACE out to 24 months and no clinically-indicated TLRs (target lesion revascularization).
How does a bioadaptor with moveable elements behave in deployment?
One of important development goals was to ensure the physician’s implantation process for DynamX was the same as their current practice. The bioadaptor’s thin 71 micron struts, the S-shaped links and the placement of the uncaging elements on the bioadaptor, crimped on a semi-compliant balloon delivery system with a small profile, provides for a device that is very flexible and deliverable across the patient’s coronary lesion. That we have made a stent-like device with best-in-class acute performance that can uncage later is still amazing to me – it stands as the first implant to adapt to patient physiology.
Tell us about the challenges of making the bioadaptor.
The concept was far easier than the implementation! Although the bioadaptor has similarities to a DES, every step of the process of making the device is more difficult than making a traditional drug-eluting stent. We had to raise the sophistication of every aspect of the device and its manufacture.
The polymer coating needed to be strong yet flexible enough to allow the bioadaptor to be crimped and then expanded in the artery, while thin enough to resorb and disengage within 6 months. We incorporated the right polymer and right thickness to accomplish this.
You have to realize that we are working with a metallic device that has uncaging elements and is designed to disengage into helical segments that fit together to maintain the longitudinal integrity of the bioadaptor. You are handling more surfaces on the bioadaptor not present on a DES. This presented challenges not only in the design, but in the manufacturing of the device. When you raise the state-of-the-art in design, you have to also raise the state-of-the-art in manufacturing. Elixir’s team had excellent capabilities in fully resorbable scaffolds, so they were up to the challenge and had the skill to also take the DynamX manufacturing process to the next level.
The ability to manufacture this novel device – consisting of 2 types of polymer coating, a drug, and a metal device with moveable elements – repeatedly and predictably is integral to its success. Enabling a seamless transition from an intact polymer-coated device to one that can uncage and move with the artery is unprecedented. The manufacturing solutions combined with the design are enabling us to avoid malapposition, thrombosis, tissue abrasion and inflammation; in fact, we have seen none of this in clinical or preclinical studies. By manufacturing a device that uncages the artery, we are able to provide benefits that extend beyond the early acute performance of DES.
How do you think the DynamX Bioadaptor will help physicians and patients?
Developing DynamX was a big challenge, but it has been worth it. The clinical data we have been seeing, now out to 24 months, is positive and very encouraging. The bioadaptor is working exactly as we designed in restoring vessel function, maintaining the ability for positive adaptive remodeling, and allowing the vessel to return toward its baseline angulation. It is gratifying to have been a part of its development from the beginning and to see its significant potential becoming a reality. Physicians now have a new innovation beyond DES to treat their CAD patients that may have long-term benefits for them.
About John Yan
John Yan is a co-founder and brings more than 30 years of experience in catheter-based medical device research and development to his role as CTO at Elixir Medical, with an expertise in engineering and application of degradable and non-degradable biomaterials. Previously, John served as Director of R&D for Avantec Vascular, and has held R&D and engineering roles at Cardiac Pathways (catheter-based electrophysiology devices), Guidant (coronary stents), Ohmeda (critical care monitoring and therapies) and Mentor (reconstructive and cosmetic implants). John holds 57 U.S. patents and has been extensively published in peer reviewed cardiovascular journals. He holds an M.S. in Bioengineering from Clemson University and a B.S. in Bioengineering from the University of California, San Diego.