Commonly Overlooked Factors in Biocompatibility Studies of Neural Implants

Abstract

Biocompatibility of cutting-edge neural implants, surgical tools and techniques, and therapeutic technologies is a challenging concept that can be easily misjudged. For example, neural interfaces are routinely gauged on how effectively they determine active neurons near their recording sites. Tissue integration and toxicity of neural interfaces are frequently assessed histologically in animal models to determine tissue morphological and cellular changes in response to surgical implantation and chronic presence. A disconnect between histological and efficacious biocompatibility exists, however, as neuronal numbers frequently observed near electrodes do not match recorded neuronal spiking activity. The downstream effects of the myriad surgical and experimental factors involved in such studies are rarely examined when deciding whether a technology or surgical process is biocompatible. Such surgical factors as anesthesia, temperature excursions, bleed incidence, mechanical forces generated, and metabolic conditions are known to have strong systemic and thus local cellular and extracellular consequences. Many tissue markers are extremely sensitive to the physiological state of cells and tissues, thus significantly impacting histological accuracy. This review aims to shed light on commonly overlooked factors that can have a strong impact on the assessment of neural biocompatibility and to address the mismatch between results stemming from functional and histological methods.

Towards detection of cancer biomarkers in human exhaled air by transfer-learning-powered analysis of odor-evoked calcium activity in rat olfactory bulb

“…In the past research, microelectrodes and microelectrode arrays were widely used to read information from the olfactory system of mammals for the recognition of volatile compounds [ 24 , 25 , 42 , 43 ]. Despite the data on the high efficiency of such systems, it should be noted that the microelectrode method is sensitive to immune responses and electrode movements, which makes it difficult to obtain neural signals for a long period of time [ [44] , [45] , [46] ]. In this paper, we take the glomerular calcium activity as a novel sensing element for optical recording.…”

Implantable neural electrodes: from preparation optimization to application

“…After one cycle of observation, the distribution of glial cells and neurons around the wound is displayed according to histological analysis and immunofluorescence staining, which is used to determine the histomorphology and cellular changes around the electrode, including detection of neuronal nuclei (NeuN), glial fibrillary acid protein (GFAP), microglial and macrophage markers (Iba1 and CD68/ED1), immunoglobulin gamma (IgG), nuclear chromatin markers (DAPI: 4′,6-diamidino-2-phenylindole) and other indicators. 186,187 The commonly used hematoxylin and eosin (HE) staining can observe the histological appearance of fibroblasts, inflammatory cells, and blood vessels, while the Masson's trichrome (MT) staining can evaluate collagen deposition and quantify the thickness of fibrous capsules. 188,189 In addition, recent reports have elucidated common and overlooked surgical factors that have a strong impact on neural biocompatibility assessment, including anesthesia, temperature excursions, bleed incidence, mechanical forces generated, and metabolic conditions, which may prevent future research from obtaining the required clinical effects.…”

“…188,189 In addition, recent reports have elucidated common and overlooked surgical factors that have a strong impact on neural biocompatibility assessment, including anesthesia, temperature excursions, bleed incidence, mechanical forces generated, and metabolic conditions, which may prevent future research from obtaining the required clinical effects. 186 In summary, except for electrodes prepared from specific materials or structures that require testing for cell adhesion, other biological methods are routine tests. Therefore, we should choose the appropriate testing method according to the needs of the experiment.…”