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Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials.

ABSTRACT: Extracellular matrix (ECM)-based implantable neural electrodes (NEs) were achieved using a microfabrication strategy on natural-substrate-based organic materials. The ECM-based design minimized the introduction of non-natural products into the brain. Further, it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions, thereby reducing inflammatory strain fields in the tissue. Preliminary studies suggested that ECM-NEs produce a reduced inflammatory response compared with inorganic rigid and flexible approaches. In vivo intracortical recordings from the rat motor cortex illustrate one mode of use for these ECM-NEs.

SUBMITTER: Shen W

PROVIDER: S-EPMC6258041 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials.

Shen Wen W Karumbaiah Lohitash L Liu Xi X Saxena Tarun T Chen Shuodan S Patkar Radhika R Bellamkonda Ravi V RV Allen Mark G MG

Microsystems & nanoengineering 20150629 1

Extracellular matrix (ECM)-based implantable neural electrodes (NEs) were achieved using a microfabrication strategy on natural-substrate-based organic materials. The ECM-based design minimized the introduction of non-natural products into the brain. Further, it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions, thereby reducing inflam ...[more]

PMID: 30498620

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Project description:Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custom-made peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM-synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicine.

Project description:Intracortical microelectrodes induce vascular injury upon insertion into the cortex. As blood vessels rupture, blood proteins and blood-derived cells (including platelets) are introduced into the 'immune privileged' brain tissues at higher-than-normal levels, passing through the damaged blood-brain barrier. Blood proteins adhere to implant surfaces, increasing the likelihood of cellular recognition leading to activation of immune and inflammatory cells. Persistent neuroinflammation is a major contributing factor to declining microelectrode recording performance. We investigated the spatial and temporal relationship of blood proteins fibrinogen and von Willebrand Factor (vWF), platelets, and type IV collagen, in relation to glial scarring markers for microglia and astrocytes following implantation of non-functional multi-shank silicon microelectrode probes into rats. Together with type IV collagen, fibrinogen and vWF augment platelet recruitment, activation, and aggregation. Our main results indicate blood proteins participating in hemostasis (fibrinogen and vWF) persisted at the microelectrode interface for up to 8-weeks after implantation. Further, type IV collagen and platelets surrounded the probe interface with similar spatial and temporal trends as vWF and fibrinogen. In addition to prolonged blood-brain barrier instability, specific blood and extracellular matrix proteins may play a role in promoting the inflammatory activation of platelets and recruitment to the microelectrode interface. STATEMENT OF SIGNIFICANCE: Implanted microelectrodes have substantial potential for restoring function to people with paralysis and amputation by providing signals that feed into natural control algorithms that drive prosthetic devices. Unfortunately, these microelectrodes do not display robust performance over time. Persistent neuroinflammation is widely thought to be a primary contributor to the devices' progressive decline in performance. Our manuscript reports on the highly local and persistent accumulation of platelets and hemostatic blood proteins around the microelectrode interface of brain implants. To our knowledge neuroinflammation driven by cellular and non-cellular responses associated with hemostasis and coagulation has not been rigorously quantified elsewhere. Our findings identify potential targets for therapeutic intervention and a better understanding of the driving mechanisms to neuroinflammation in the brain.

Project description:OBJECTIVE:Our objective was to determine how readily disruption of the blood-brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature. APPROACH:We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1?h after the craniotomy procedure using Evans blue dye. MAIN RESULTS:Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from??+3 °C to??+21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation. SIGNIFICANCE:Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during 'off' periods. While saline alone was ineffective at preventing overheating, its use is still recommended to remove bone dust from the surgical site and to augment other cooling methods.

Dataset Information

Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials.

Publications

Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials.

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