In situ characterization of the brain–microdevice interface using Device Capture Histology

Abstract

Accurate assessment of brain-implantable microdevice bio-integration remains a formidable challenge. Prevailing histological methods require device extraction prior to tissue processing, often disrupting and removing the tissue of interest which had been surrounding the device. The Device-Capture Histology method, presented here, overcomes many limitations of the conventional Device-Explant Histology method, by collecting the device and surrounding tissue intact for subsequent labeling. With the implant remaining in situ, accurate and precise imaging of the morphologically preserved tissue at the brain/microdevice interface can then be collected and quantified. First, this article presents the Device-Capture Histology method for obtaining and processing the intact, undisturbed microdevice-tissue interface, and images using fluorescent labeling and confocal microscopy. Second, this article gives examples of how to quantify features found in the captured peridevice tissue. We also share histological data capturing 1) the impact of microdevice implantation on tissue, 2) the effects of an experimental anti-inflammatory coating, 3) a dense grouping of cell nuclei encapsulating a long-term implant, and 4) atypical oligodendrocyte organization neighboring a longterm implant. Data sets collected using the Device-Capture Histology method are presented to demonstrate the significant advantages of processing the intact microdevice-tissue interface, and to underscore the utility of the method in understanding the effects of the brain-implantable microdevices on nearby tissue.

A living electrode construct for incorporation of cells into bionic devices

“…[3,4] It is known that an implant requires a modulus higher than that of the neural tissue to facilitate an accurate and low damage insertion; however, the ongoing presence of stiff materials will impart a frustrated immune response and hence generate scar tissue. [3] It should be noted that the living electrode construct is not designed to be implanted on the day it is fabricated. The cells encapsulated within the surface of the device must be placed in an incubator for 24-48 h post-fabrication.…”

“…[1,2] The consequences of this mode of operation is that chronic frustration of the wound-healing process produces a scar tissue reaction, which encapsulates the implant and electrically isolates it from the target tissue. [3,4] As a result, the amount of charge required to activate the target tissue often increases over time and the implant loses efficacy. [5,6] Rather than relying on unwieldy metal electrodes and direct charge injection, tissue-engineered bioelectronics will use cells embedded within devices to provide a natural mode of physiologic tissue activation.…”

A critical review of cell culture strategies for modelling intracortical brain implant material reactions

“…The most prominent cell type responding to these gradients are astrocytes. The astrocytic reaction is readily documented histologically from in vivo experiments [19] and modelled in vitro [36]. During the healing process, astrocytes within the penumbra undergo graded levels of reactive astrocytosis.…”

“…The biological response to device implantation and its chronic presence results in a complex array of reactions that can contribute to device failure in time frames from a few weeks to years [16e18]. Studying the causes and the sources of these reactions in vivo is challenging for a number of reasons including myriad challenges associated with methods of tissue assessment [19], animal welfare, limited experimental control, and cost of experiments [20]. Investigation of the biological reactions has the potential to provide insight into this failure mechanism however data from both in vivo and in vitro research currently do not provide clear answers.…”

“…The collection, processing and imaging of histological samples from in vivo experiments have significant limitations, as discussed in Woolley et al [19]. Few in vivo studies have successfully followed the cellular/tissue reactions around cortical implants over time, and each of these studies has significant limitations.…”