Christopher Cheng, Ph.D., Valerie Merkle, Ph.D.
This is the first of five short articles on the importance of cardiovascular device biomechanical compatibility. These articles discuss: 1) why biomechanical compatibility is important, 2) its role in the device development process, 3) fatigue evaluation for initiating clinical trials, 4) fatigue evaluation for market approval, and 5) the future of biomechanical compatibility assessment.
Function and Accommodation
Cardiovascular medical devices are invented and used for a myriad of reasons. They maintain blood vessel flow lumens, exclude aneurysms and dissections, close orifices and communications, and even completely replace the function of valves, vessels, and membranes. However, with focused attention on the implant's primary functions, it is easy forget that an implant also has secondary objectives – to do no harm and stay intact. While loss of device integrity may not lead to immediate clinical sequelae, the potential risk for such events may increase over the lifetime of the device. Ultimately, each device is designed to do something, but it can only keep performing its primary function if it adequately accommodates its environment.
Interactions between Device and Environment
Implants come in many forms, making their interactions with the human body as varied as physiologic phenomena and the patient population. Devices need to pulse with the cardiac cycle, conform and flex with respiration, and stretch, shorten, crush, bend, and twist with joint motion and muscular contraction. We know a lot about how implants behave in some anatomies through decades of research, such as stents in the coronary and superficial femoral arteries. However, we know very little about how devices interact with their environment in novel applications, such as devices that occupy veins or cross between chambers of the heart. For these novel applications, it is even more important to complete appropriate research to develop a greater understanding of the in vivo environments to which the devices will be exposed.
The Tripod – Loading Conditions, Computational Modeling, Benchtop Testing
Loading conditions come in different flavors: displacement-controlled, force-controlled, and mixed. A displacement-controlled loading condition will deform any device agnostically regardless of its mechanical properties, while a force-controlled condition will cause deformation commensurate with device stiffness. The human cardiovascular system tends to mix these two types of conditions, making device deformations difficult to predict. However, with focused preclinical, cadaver, or clinical observations, realistic loading conditions can be developed and used to properly predict stress and strain through computational modeling, and then confirm and interpret those stresses and strains using benchtop testing and materials science concepts. The result is an evaluation of mechanical durability.
Mechanical Durability vs. Biomechanical Harmony
Besides mechanical durability, the other piece of biomechanical compatibility is biomechanical harmony. An implant can be designed to be so stiff that it would not deform due to any physiologic motion. Without deformation, there can be no stress or strain (at least in normal circumstances in the body), so there can be no mechanical fatigue. However, this type of rigid device could cause tissue trauma or irritation, e.g. a rigid stent could cause vessel kinking at the transition between the stent and the native vessel, which could lead to restenosis, dissection, aneurysm, or rupture. Every device will impact the mechanical environment of the anatomy where it resides, and considerations to the intended in vivo environment should be made to minimize adverse events to the patients receiving the device.
Importance of Mechanical Durability
Mechanical durability that addresses relevant loading modes is an important aspect of a device evaluation strategy. While clinical study data provides a real assessment of mechanical durability in the intended conditions of use, clinical studies to support marketing approval or clearance are generally designed with the primary analysis at shorter-term implant durations (e.g., 1 year). Therefore, the mechanical durability evaluation provides insights into the long-term fatigue performance of the device to further support placing it on the market.
The What, The How, The Why
Designers of any device, medical or otherwise, need to know WHAT they are building. The deeper question of HOW they build it sets them apart from their competitors by being able to manufacture better products, and perhaps even make a profit in the meantime. But the deepest question of WHY they are building their device reveals what truly distinguishes outstanding products from others. One of the reasons why all of us participate in the healthcare industry is to help improve and save lives. We do not treat disease; we treat patients. Great medical devices do not only treat ailments – they also function for a lifetime and interact with the body harmoniously.
About the Authors
Dr. Christopher Cheng has 20+ years of experience in academic research and the medical device industry, spanning hemodynamics, vascular motion, device design, manufacturing, preclinical testing, clinical trials, and marketing. He is considered the preeminent expert in vascular motion, having over 100 publications and edited Handbook of Vascular Motion (PROSE Book Award Nominee, https://www.elsevier.com/books/handbook-of-vascular-motion/cheng/978-0-1...), the first and only book dedicated to how blood vessels move. Dr. Cheng runs the Global Science & Technology – Medical Division (gst.com/med), the first dedicated organization to help medical device companies holistically evaluate and improve biomechanical compatibility of medical implants. He is also an Adjunct Professor in the Division of Vascular Surgery at Stanford, Director of the Vascular Intervention Biomechanics & Engineering (VIBE) lab (vibelab.stanford.edu), and Director of the Cardiovascular Implant Durability Conference (cvidconference.org). Previously, Dr. Cheng was co-founder and CEO of Kōli, Inc., an early-stage medical device company developing a catheter-based solution for gallstone disease. Dr. Cheng studied BME and EE at Duke University, earned his Master's and Ph.D. in Biomechanics at Stanford University, and currently serves as a board member of the Duke University Pratt School of Engineering.
Dr. Valerie Merkle is the Associate Director of Regulatory Strategy at Syntactx. With the Syntactx Team, she provides expert assistance to clients seeking regulatory approvals and product adoption worldwide. Prior to joining Syntactx, Dr. Merkle was a leader in the U.S. Food and Drug Administration (FDA) in the Center for Devices and Radiological Health (CDRH) vascular and endovascular surgical devices team. In her role, she managed and reviewed over 650 complex regulatory submissions, including pre-submissions, investigational device exemptions, as well as 510(k) and PMA marketing submissions. Her FDA experience included managing challenging submissions for first-of-a-kind devices and those with unique benefit/risk profiles, providing her the opportunity to serve as the FDA lead to a meeting of the Circulatory System Devices Panel. Her additional expertise and outreach include standards work, cardiovascular materials research, and FDA/external research collaborations. Dr. Merkle is a Steering Committee Member for the Greenberg Stent Summit, a unique conference that brings together representatives from industry, clinical practice, and FDA to discuss current issues in endovascular interventional therapy. Dr. Merkle holds a Bachelor of Science in Chemical Engineering from Bucknell University, a Ph.D. in Biomedical Engineering from the University of Arizona, and is an Innovation Fellow of the Fogarty Institute. She has co-authored numerous peer-reviewed manuscripts and has presented at multiple academic, scientific, and technical conferences.