81 research outputs found
A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex
The viability of chronic neural microelectrodes for electrophysiological recording and stimulation depends on several factors, including the encapsulation of the implant by a reactive tissue response. We postulate that mechanical strains induced around the implant site may be one of the leading factors responsible for the sustained tissue response in chronic implants. The objectives of this study were to develop a finite-element model of the probe–brain tissue interface and analyze the effects of tethering forces, probe–tissue adhesion and stiffness of the probe substrate on the interfacial strains induced around the implant site. A 3D finite-element model of the probe–brain tissue microenvironment was developed and used to simulate interfacial strains created by ‘micromotion’ of chronically implanted microelectrodes. Three candidate substrates were considered: (a) silicon, (b) polyimide and (c) a hypothetical ‘soft’ material. Simulated tethering forces resulted in elevated strains both at the tip and at the sharp edges of the probe track in the tissue. The strain fields induced by a simulated silicon probe were similar to those induced by a simulated polyimide probe, albeit at higher absolute values for radial tethering forces. Simulations of poor probe–tissue adhesion resulted in elevated strains at the tip and delamination of the tissue from the probe. A tangential tethering force results in 94% reduction in the strain value at the tip of the polyimide probe track in the tissue, whereas the simulated ‘soft’ probe induced two orders of magnitude smaller values of strain compared to a simulated silicon probe. The model results indicate that softer substrates reduce the strain at the probe–tissue interface and thus may also reduce tissue response in chronic implants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49186/2/jne5_4_006.pd
High-frequency spinal cord stimulation at 10 kHz for the treatment of painful diabetic neuropathy: design of a multicenter, randomized controlled trial (SENZA-PDN)
Background:
Painful diabetic neuropathy (PDN), a debilitating and progressive chronic pain condition that significantly impacts quality of life, is one of the common complications seen with long-standing diabetes mellitus. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) has provided significant and long-term pain relief for patients with PDN. This study aims to document the value of 10-kHz SCS in addition to conventional medical management (CMM) compared with CMM alone in patients with refractory PDN.
Methods:
In a prospective, multicenter, randomized controlled trial (SENZA-PDN), 216 subjects with PDN will be assigned 1:1 to receive 10-kHz SCS combined with CMM or CMM alone after appropriate institutional review board approvals and followed for 24 months. Key inclusion criteria include (1) symptoms of PDN for at least 12 months, (2) average pain intensity of at least 5 cm—on a 0- to 10-cm visual analog scale (VAS)—in the lower limbs, and (3) an appropriate candidate for SCS. Key exclusion criteria include (1) large or gangrenous ulcers or (2) average pain intensity of at least 3 cm on VAS in the upper limbs or both. Along with pain VAS, neurological assessments, health-related quality of life, sleep quality, and patient satisfaction will be captured. The primary endpoint comparing responder rates (≥50% pain relief) and safety rates between the treatment groups will be assessed at 3 months. Several secondary endpoints will also be reported on.
Discussion:
Enrollment commenced in 2017 and was completed in 2019. This study will help to determine whether 10-kHz SCS improves clinical outcomes and health-related quality of life and is a cost-effective treatment for PDN that is refractory to CMM
Silk as a Multifunctional Biomaterial Substrate for Reduced Glial Scarring around Brain‐Penetrating Electrodes
The reliability of chronic, brain‐penetrating electrodes must be improved for these ‐neural recording technologies to be viable in widespread clinical applications. One approach to improving electrode reliability is to reduce the foreign body response at the probe‐tissue interface. In this work, silk fibroin is investigated as a candidate material for fabricating mechanically dynamic neural probes with enhanced biocompatibility compared to traditional electrode materials. Silk coatings are applied to flexible cortical electrodes to produce devices that transition from stiff to flexible upon hydration. Theoretical modeling and in vitro testing show that the silk coatings impart mechanical properties sufficient for the electrodes to penetrate brain tissue. Further, it is demonstrated that silk coatings may reduce some markers of gliosis in an in vitro model and that silk can encapsulate and release the gliosis‐modifying enzyme chondroitinase ABC. This work establishes a basis for future in vivo studies of silk‐based brain‐penetrating electrodes, as well as the use of silk materials for other applications in the central nervous system where gliosis must be controlled. Silk fibroin is investigated as a novel material for fabricating brain‐penetrating electrodes with dynamic mechanical properties and the capacity to deliver sensitive therapeutics. Silk coatings are shown to natively reduce some markers of gliosis in vitro, and a further reduction is demonstrated by encapsulation and release of the enzyme chondroitinase ABC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98822/1/3185_ftp.pd
SU-8 based microprobes for simultaneous neural depth recording and drug delivery in the brain
Nanomaterials for Neural Interfaces
This review focuses on the application of nanomaterials for neural interfacing. The junction between nanotechnology and neural tissues can be particularly worthy of scientific attention for several reasons: (i) Neural cells are electroactive, and the electronic properties of nanostructures can be tailored to match the charge transport requirements of electrical cellular interfacing. (ii) The unique mechanical and chemical properties of nanomaterials are critical for integration with neural tissue as long-term implants. (iii) Solutions to many critical problems in neural biology/medicine are limited by the availability of specialized materials. (iv) Neuronal stimulation is needed for a variety of common and severe health problems. This confluence of need, accumulated expertise, and potential impact on the well-being of people suggests the potential of nanomaterials to revolutionize the field of neural interfacing. In this review, we begin with foundational topics, such as the current status of neural electrode (NE) technology, the key challenges facing the practical utilization of NEs, and the potential advantages of nanostructures as components of chronic implants. After that the detailed account of toxicology and biocompatibility of nanomaterials in respect to neural tissues is given. Next, we cover a variety of specific applications of nanoengineered devices, including drug delivery, imaging, topographic patterning, electrode design, nanoscale transistors for high-resolution neural interfacing, and photoactivated interfaces. We also critically evaluate the specific properties of particular nanomaterials—including nanoparticles, nanowires, and carbon nanotubes—that can be taken advantage of in neuroprosthetic devices. The most promising future areas of research and practical device engineering are discussed as a conclusion to the review.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64336/1/3970_ftp.pd
SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording
Development of a stimuli-responsive polymer nanocomposite toward biologically optimized, MEMS-based neural probes
A randomized controlled trial of high frequency (10 kHz) spinal cord stimulation in painful diabetic neuropathy
Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.
Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN).
Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated.
Interventions: Implanted medical device delivering 10-kHz SCS.
Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months.
Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001).
Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN.
Trial Registration: ClincalTrials.gov Identifier: NCT0322842
Investigations of tethering induced injury response in brain tissue by intracortical implants through modeling and in vivo experiments.
One of the limitations of intracortical microelectrodes in chronic applications is their inability to transduce signals of interest for sustained periods of time. Of the many failure modes, the chronic tissue response (CTR) evoked by the continued presence of these sensors in the brain tissue is of particular interest to neural engineers. Thus mitigating this response is of the utmost importance in furthering the usage of these implants for chronic applications. In this study, the effect of relative motion of implants with respect to brain tissue (micromotion) in inducing CTR was tested by (1) developing a finite-element model to simulate interfacial strain induced by micromotion and quantifying the injury response evoked by (2) implants in three tethering configurations and (3) stiff and flexible implant substrates through quantitative immunohistochemistry (IHC). Results from these experiments are detailed below. (1) A 3-D finite-element model of the probe-brain tissue microenvironment was developed and three candidate substrates were simulated. A tangential tethering force resulted in 94% reduction in strain value at the tip of the polyimide probe track in the tissue, whereas the simulated soft probe induced two orders of magnitude smaller values of strain compared to a simulated silicon probe. (2) Untethered implants caused significantly smaller neuronal loss than both conventionally tethered and flexibly tethered implants in the first 25 mum from the implant-tissue interface (32%, 56% and 54%, respectively) (p < 0.05). Based on the evidence, the sustained presence of a transcranial interconnect attached to an implant is believed to be more important in determining the injury response than the interconnect flexibility in chronic intracortical implants. (3) Rigid (parylene) implants caused significantly smaller neuronal loss and smaller increase in non-neuronal cells than flexible (polydimethylsiloxane) implants. The apparent contradiction was explained by the hydrophobic nature and the resulting adsorption of proteins onto the PDMS substrate. The results suggest that modulating mechanical stiffness of implant materials alone has limited effect on CTR and that a complex problem like this could be best addressed by a combination of techniques.Ph.D.Applied SciencesBiological SciencesBiomedical engineeringNeurosciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126570/2/3253413.pd
Report f the conference on physical Education held at Madras on the 14th and 15th October 1927
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