The data generated from the histopathology pipeline provides a comprehensive assessment of the medical device’s impact on the tissue, encompassing a wide array of imaging and analysis techniques. Gross images serve as the initial step, helping to identify the stereo offset of the device in contact with the tissue, any mechanical damages or degradation of the material, and the gross severity of the implant site. These images are crucial for recording abnormalities that could be systematically related to the extractables and leachables from the device, offering an early indication of potential issues.

Advancements in digital imaging allow for the creation of whole slide images, captured using a digital microscope slide scanner. These images can be analyzed through various modalities, including brightfield, fluorescent, and polarized light, providing detailed insights into the tissue-device interface. Complementary imaging read-outs further enhance the evaluation, incorporating techniques such as radiographic imaging (MRI, uMRI, CT, uCT, PET), electron microscopy, high-frequency ultrasound, elemental analysis (MaltiToF), and spatial transcriptomics (10x Visium), each offering unique perspectives on the device’s impact.

Image analysis (IA) quantitatively assesses the presence of the implanted material and the extent of pathology, including necrosis, tissue-specific cell loss, chronic inflammation, and fibrosis. This quantification allows for an objective assessment of the device’s safety and effectiveness.

The culmination of this process is the pathology report, a critical, unbiased document that assesses the device’s safety preclinically. It synthesizes surgical pathological reports, clinical observations, necropsy findings, and microscopic slide data to summarize any severe pathology that may have arisen due to contact with the device. Tissues are typically stained hematoxylin and eosin (H&E) and scored semi-quantitatively on a severity scale ranging from 0 to 4, providing a clear, standardized measure of the device’s biological impact. This comprehensive approach ensures a thorough evaluation of the medical device’s safety, guiding future development and regulatory approval processes.