Medical Device Histology and Pathology: A Horse of a Different Color

Abstract

Medical devices comprise a wide variety of therapeutic tools aimed at modulating or restoring organ function. Devices may be implanted or activated temporally or permanently, and are used to deliver a wide range of therapies such as drugs, electrical stimulation, laser, thermal energy, offer mechanical support, and restore sensory functions. Technological advancements allow improvement and development of devices at a rapid pace. This special issue of Toxicologic Pathology addresses a need for more publications focused on pathology evaluation of medical devices in preclinical studies and highlights fundamental approaches through practical examples bringing into perspective the essential role of pathologists in this field.

Medical devices comprise a multitude of medical tools that range from prosthetics to systems that can deliver various types of therapies including drugs, electrical stimulations, laser, mechanical, or chemical sensors. In modern history, the role of medical devices is rapidly expanding, and they are becoming essential in the therapeutic arsenal to treat diseases and extend life.

Technological advancements in biomaterial engineering, miniaturization of electronics, and in material sciences are enabling great improvement in next-generation medical devices such as miniaturized leadless cardiac pace markers, transcatheter-delivered heart valves, and neurothrombectomy devices for ischemic stroke treatment. Such advancements facilitate the design of an ever-expanding array of novel devices used to modulate or replace organ functions and restore health.

As practicing medical device pathologists, it has been our perception that there is a need for more publications focused on preparation techniques and pathology assessment of devices in preclinical studies. With this special issue of Toxicologic Pathology, we have attempted to address a few of the existing gaps and highlight the pathologist role in the evaluation of a variety of devices. Given the multitude of medical device types and designs and their different modalities of therapy delivery, it is impossible to cover all aspects and all medical devices in a single issue. We hope this issue of Toxicologic Pathology will provide a methodological framework and motivate our colleagues to continue publishing in this area and bring more point of views on current practices.

In most medical device studies, a detailed gross evaluation of the implant site is often critical to pathology interpretation and safety assessment. Gross examination and tissue trimming procedures must often be nondestructive and be designed to minimize artifacts and maintain tissue–device relationship. These special predicaments require that all staff involved from necropsy, through histology and pathology evaluation, be fully aware of device design, model, and protocol-specific requirements. Collaborative teamwork from the time of study design/plan to the time of final study report is essential to success. Additionally, in-life data such as imaging (CT scans, MRI, and echocardiography) and surgical reports often provide information that is essential to the success of the pathology work. For example, variations in surgical procedure, excessive trauma, proper device function, or device design/shape among other factors can impact tissue response and dictate sampling strategy.

Given the multitude of medical devices, guidelines and standards for pathology evaluation, such as ISO10993-6 International Standard (ISO Technical Committee, 2016), provide a basic framework, which is useful but lack details and sometimes relevant nuances with regard to pathology. There is no substitute to solid pathology training, experience, and plain common sense to inform and guide the optimal way to plan a study and assess a device in tissue. Such competencies by the pathologist are developed over time and collaboratively with other scientific disciplines to include interaction with material engineers, surgeons, interventionalists, imaging specialists, and regulatory experts.

Hence, there are instances in which the pathologist may propose, with reasonable justification, deviations from published guidelines or standards in order to enhance the evaluation and ensure patient safety. This special issue will present a few of these necessary accommodations and customizations.

This special issue on the pathology of medical devices is dedicated to the memory of Donald F. Gibbons, PhD, DSc (1926–2018): scientist, renaissance man, pioneer, and mentor to many. Dr. Gibbons (Figure 1) received a PhD in metallurgy from Birmingham University. While as a director at the Center for the Study of Materials, Case Western Reserve University, Cleveland, Ohio, in the 1960s, he foresaw the future of biomaterials and the importance of biocompatibility assessment and was one of the founders of the Department of Biomedical Engineering and the Society for Biomaterials. He understood the need for being meticulous at a basic scientific level whether it was about the structure–property relationships of materials and how they influence biological pathways or the need for deeper understanding of tissue interactions. He saw how the biologic environment influences cell’s characteristics or traits (i.e., phenotype) and was prescient in his observation of pluripotential mononuclear cells. His hobby was the metallurgy of ancient art objects! When he retired, he was a key contributor to ASM Internationals Materials for Medical Devices Database. Several contributors to this issue were fortunate to be able to know Don as a colleague, mentor, and friend, and he is greatly missed by all who knew him.

Figure 1.

Donald F. Gibbons, PhD, DSc (1926–2018).