considerations for medical device histology tissue preparation

Histology is a critical step for any preclinical study when bringing a medical device to market and should not be overlooked when considering development timelines. Tissue histology provides U.S. Food and Drug Administration (FDA) regulators with physical evidence, down to the cellular level, regarding how a device interacts with tissue. If histology results show no signs of adverse events (AEs) in relation to a specific device, a manufacturer’s case is strengthened with regulators and indicates that said device is ready for human clinical trials.

In the following blog, NAMSA highlights histology techniques that are utilized to prepare preclinical study tissue for histological analyses through tissue fixation, embedding and sectioning.

I. HISTOLOGY PREPARATION: TISSUE FIXATION AND EMBEDDING

A. Paraffin-Embedded Tissue Blocks 

Following tissue fixation, most commonly with 10% neutral buffered formalin (NBF), the preserved tissue is dehydrated, cleared and embedded into paraffin wax to create what is called ‘Formalin-Fixed Paraffin-Embedded’ (FFPE) tissue.

FFPE tissue blocks are the most common preservation method in medical histology, typically used for light microscopy observation and for tissue-only histology studies where a test device can be easily removed without tissue damage.

However, in some cases, paraffin-embedded samples of the device can be created as long as it’s made of softer materials, such as silicone, that can easily be cut into thin ribbons with a microtome blade during sectioning.

It is important to note that timing is a critical factor in the FFPE tissue process. Tissue must be placed in fixative soon after excision; complete fixation takes a minimum of 48 hours depending on the size and density of the tissue. From the time tissue is obtained to the draft pathology report, a paraffin study typically takes 8-10 weeks.

B. Spurr’s Embedding (Plastic Embedding) 

Plastic embedding is a more labor-intensive process requiring special equipment. It is best used for electron microscopy and for histology studies where it’s impossible to remove a test device without harming the tissue.

At this stage, the plastic embedding has an advantage because you can directly evaluate the tissue and device interaction.

C. OCT Embedding

‘OCT’ stands for Optimal Cutting Temperature compound. This is a quick embedding process for frozen tissues and it’s deployed to fulfill certain requirements such as an enzymatic analysis. This embedding method does not require fixed tissue and involves snap freezing the tissue using liquid nitrogen. OCT is a less common embedding technique, but it is an option when paraffin and epoxy resin embedding may destroy certain tissue elements.

II. THE PROCESS OF TISSUE SECTIONING

Following sample fixation and embedding, the next step is to cut tissue blocks into thin sections so they’re viewable under a microscope. The goal is to slice them to approximately one cell layer thick so the light can pass through and a device’s effects on tissue cells are visible under a microscope.

Here’s a look at NAMSA’s histology sectioning techniques:

• NAMSA’s microtome devices are capable of slicing paraffin or plastic blocks into ultra-thin ribbons, narrower than the width of a human hair, usually between 4-6 microns thick.
• The EXAKT grinding technique is a unique service that NAMSA offers. It utilizes a bandsaw with a diamond blade and a grinder with various grits of grinding and polishing papers. It makes it possible to make slides from the plastic embedded hard-alloy device and tissue that are apppoximately 70 microns thick.
• Cryosectioning is used for frozen tissue sections; it is a microtome that’s used in a cold chamber. Tissues for enzymatic evaluation are cut between 8-12 microns thick.

Histology is a labor-intensive, precise process that can’t be rushed. However, the outcome will make this portion of your development project worthwhile as it presents required physical evidence regarding product safety and efficacy to the U.S. FDA and other regulatory entities.

How Can NAMSA Help?
When it comes to successful research studies, experience matters. NAMSA has amassed the largest breadth and depth of therapeutic expertise and knowledge, more than any other preclinical development partner in industry. NAMSA’s preclinical research and histology services provide support for all model types, treatments and implant requirements, including the areas of: Cardiovascular, Dental, Dermal, Electrophysiology, Gastrointestinal, Neuromodulation, Orthopedics, Pulmonary, Urogenital, Wound Healing and several others.

To learn more about NAMSA’s pathology lab, operated by Board Certified Histotechnicians, Veterinary Pathologists, and MD/PhD Pathologists, we invite you to visit https://namsa.com/services/preclinical-research/

Complimentary Consultations
Be sure to schedule your 30-minute complimentary consultation to learn about our full suite of preclinical research solutions and how we can successfully lead you through all phases of your preclinical research project: https://namsa.com/locations-contact/.