Biomimetic extracellular matrix coatings improve the chronic biocompatibility of microfabricated subdural microelectrode arrays

Abstract

Intracranial electrodes are a vital component of implantable neurodevices, both for acute diagnostics and chronic treatment with open and closed-loop neuromodulation. Their performance is hampered by acute implantation trauma and chronic inflammation in response to implanted materials and mechanical mismatch between stiff synthetic electrodes and pulsating, natural soft host neural tissue. Flexible electronics based on thin polymer films patterned with microscale conductive features can help alleviate the mechanically induced trauma; however, this strategy alone does not mitigate inflammation at the device-tissue interface. In this study, we propose a biomimetic approach that integrates microscale extracellular matrix (ECM) coatings on microfabricated flexible subdural microelectrodes. Taking advantage of a high-throughput process employing micro-transfer molding and excimer laser micromachining, we fabricate multi-channel subdural microelectrodes primarily composed of ECM protein material and demonstrate that the electrochemical and mechanical properties match those of standard, uncoated controls. In vivo ECoG recordings in rodent brain confirm that the ECM microelectrode coatings and the protein interface do not alter signal fidelity. Astrogliotic, foreign body reaction to ECM coated devices is reduced, compared to uncoated controls, at 7 and 30 days, after subdural implantation in rat somatosensory cortex. We propose microfabricated, flexible, biomimetic electrodes as a new strategy to reduce inflammation at the device-tissue interface and improve the long-term stability of implantable subdural electrodes.

Minimal Tissue Reaction after Chronic Subdural Electrode Implantation for Fully Implantable Brain–Machine Interfaces

“…Increased thickness of the dural membrane and fibrous encapsulation of the electrode array that were found in this study have been widely reported in other chronic ECoG implantation studies for both epidural and subdural placement [23][24][25][26]. We further quantitatively measured the thickness of the reactive tissues in the subdural space and found statistically significant differences compared with the control dural membrane.…”

“…Several animal models have been established in preclinical research because of their relatively suitable skull sizes for implanted devices [ 23 , 24 , 26 , 39 , 40 , 41 , 42 ]. Minipigs and sheep have been used in studies of cuff electrodes and the WIMAGINE epidural ECoG system [ 25 , 43 ] to mimic the implantation of clinical devices.…”

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes

“…The growing scientific interest in neural interfaces in the last decades is confirmed by the multitude of in vivo works focused on the testing of new and fully biocompatible coatings (Du et al, 2017; Spencer et al, 2017b; Shen et al, 2018; Vitale et al, 2018), less invasive implantation strategies (Tawakol et al, 2016; Shoffstall et al, 2018b) and new designs with improved electrical performance (Ferlauto et al, 2018; Xu et al, 2018) and with longer durability.…”

The Future of Neuroimplantable Devices: A Materials Science and Regulatory Perspective

“…[52] Another study showed that coatings made of extracellular matrix (ECM) hydrogels, such as collagen and fibronectin, improve chronic biocompatibility of subdural ECoG arrays. [53] While coatings can improve the biocompatibility and signalto-noise ratio of a neuroimplantable device, neural foreign body response hinges more crucially on the form factor and material choices for a neuroimplantable device. Figure 2 summarizes the existing state of neuroimplantable devices, where each device is depicted with its target region in the brain, along with its form factor and materials choices.…”