Browsing by Author "Williams, Richard"

Now showing 1 - 11 of 11
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    Biocompatibility of Immobilized Aligned Carbon Nanotubes
    (Wiley, 2011) Nayagam, David; Williams, Richard; Chen, Jun; Magee, Kylie; Irwin, Jennifer; Tan, Justin; Innis, Peter; Leung, Ronald; Finch, Sue; Williams, Chris; Clark, Graeme; Wallace, Gordon
    In vivo host responses to an electrode-like array of aligned carbon nanotubes (ACNTs) embedded within a biopolymer sheet are reported. This biocompatibility study assesses the suitability of immobilized carbon nanotubes for bionic devices. Inflammatory responses and foreign-body histiocytic reactions are not substantially elevated when compared to negative controls following 12 weeks implantation. A fibrous capsule isolates the implanted ACNTs from the surrounding muscle tissue. Filamentous nanotube fragments are engulfed by macrophages, and globular debris is incorporated into the fibrous capsule with no further reaction. Scattered leukocytes are observed, adherent to the ACNT surface. These data indicate that there is a minimal local foreign-body response to immobilized ACNTs, that detached fragments are phagocytosed into an inert material, and that ACNTs do not attract high levels of surface fouling. Collectively, these results suggest that immobilized nanotube structures should be considered for further investigation as bionic components.
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    Development and Characterization of a Sucrose Microneedle Neural Electrode Delivery System
    (Wiley, 2017-12) Apollo, Nicholas; Jiang, Jonathon; Cheung, Warwick; Baquier, Sebastien; Lai, Alan; Mirebedini, Azadeh; Foroughi, Javad; Wallace, Gordon; Shivdasani, Mohit; Prawer, Steven; Chen, Shou; Williams, Richard; Cook, Mark; Nayagam, David; Garrett, David
    Stable brain–machine interfaces present extraordinary therapeutic and scientific promise. However, the electrode–tissue interface is susceptible to instability and damage during long-term implantation. Soft, flexible electrodes demonstrate improved longevity, but pose a new challenge with regard to simple and accurate surgical implantation. A high aspect ratio water-soluble microneedle is developed based on sucrose which permits straightforward surgical implantation of soft, flexible microelectrodes. Here, a description of the microneedle manufacturing process is presented, along with in vitro and in vivo safety and efficacy assessments. Successful fabrication requires control of the glass transition temperature of aqueous sucrose solutions. The insertion force of 5 different microneedle electrode vehicles is studied in agarose brain phantoms, with the sucrose microneedle eliciting the lowest insertion force and strain energy transfer. Short- and long-term assessments of the pathological response to sucrose microneedle implantations in the brain suggest minimal tissue reactions, comparable to those observed following stainless-steel hypodermic needle punctures. Finally, microelectrodes fabricated from graphene, carbon nanotubes, or platinum are embedded in sucrose microneedles and implanted into an epileptic rat model for 22 d. All electrodes are functional throughout the implantation period, with the graphene electrode exhibiting the largest seizure signal-to-noise ratio and only modest changes in impedance.
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    Hermetic diamond capsules for biomedical implants enabled by gold active braze alloys
    (Elsevier, Ltd., 2015-03) Lichter, Samantha; Escudie, Mathilde; Stacey, Alastair; Ganesan, Kumaravelu; Fox, Kate; Ahnood, Arman; Apollo, Nicholas; Kua, Dunstan; Lee, Aaron; McGowan, Ceara; Saunders, Alexia; Burns, Owen; Nayagam, David; Williams, Richard; Garrett, David; Meffin, Hamish; Prawer, Stephen
    As the field of biomedical implants matures the functionality of implants is rapidly increasing. In the field of neural prostheses this is particularly apparent as researchers strive to build devices that interact with highly complex neural systems such as vision, hearing, touch and movement. A retinal implant, for example, is a highly complex device and the surgery, training and rehabilitation requirements involved in deploying such devices are extensive. Ideally, such devices will be implanted only once and will continue to function effectively for the lifetime of the patient. The first and most pivotal factor that determines device longevity is the encapsulation that separates the sensitive electronics of the device from the biological environment. This paper describes the realisation of a free standing device encapsulation made from diamond, the most impervious, long lasting and biochemically inert material known. A process of laser micro-machining and brazing is described detailing the fabrication of hermetic electrical feedthroughs and laser weldable seams using a 96.4% gold active braze alloy, another material renowned for biochemical longevity. Accelerated ageing of the braze alloy, feedthroughs and hermetic capsules yielded no evidence of corrosion and no loss of hermeticity. Samples of the gold braze implanted for 15 weeks, in vivo, caused minimal histopathological reaction and results were comparable to those obtained from medical grade silicone controls. The work described represents a first account of a free standing, fully functional hermetic diamond encapsulation for biomedical implants, enabled by gold active alloy brazing and laser micro-machining.
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    In vivo biocompatibility of boron doped and nitrogen included conductive-diamond for use in medical implants
    (John Wiley & Sons Inc, 2015-01) Garrett, David; Saunders, Alexia; McGowan, Ceara; Specks, Joscha; Ganesan, Kumaravelu; Meffin, Hamish; Williams, Richard; Nayagam, David
    Recently, there has been interest in investigating diamond as a material for use in biomedical implants. Diamond can be rendered electrically conducting by doping with boron or nitrogen. This has led to inclusion of boron doped and nitrogen included diamond elements as electrodes and/or feedthroughs for medical implants. As these conductive device elements are not encapsulated, there is a need to establish their clinical safety for use in implants. This article compares the biocompatibility of electrically conducting boron doped diamond (BDD) and nitrogen included diamond films and electrically insulating poly crystalline diamond films against a silicone negative control and a BDD sample treated with stannous octoate as a positive control. Samples were surgically implanted into the back muscle of a guinea pig for a period of 4-15 weeks, excised and the implant site sectioned and submitted for histological analysis. All forms of diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating compared to the silicone negative control samples. All forms of diamond exhibited similar or lower levels of acute, chronic inflammatory, and foreign body responses compared to the silicone negative control indicating that the materials are well tolerated in vivo. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
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    In vivo biocompatibility of boron doped and nitrogen included conductive-diamond for use in medical implants
    (Wiley Online Library, 2015-01-21) Garrett, David; Saunders, Alexia; McGowan, Ceara; Specks, Joshua; Ganesan, Kumaravelu; Meffin, Hamish; Williams, Richard; Nayagam, David
    Recently, there has been interest in investigating diamond as a material for use in biomedical implants. Diamond can be rendered electrically conducting by doping with boron or nitrogen. This has led to inclusion of boron doped and nitrogen included diamond elements as electrodes and/or feedthroughs for medical implants. As these conductive device elements are not encapsulated, there is a need to establish their clinical safety for use in implants. This article compares the biocompatibility of electrically conducting boron doped diamond (BDD) and nitrogen included diamond films and electrically insulating poly crystalline diamond films against a silicone negative control and a BDD sample treated with stannous octoate as a positive control. Samples were surgically implanted into the back muscle of a guinea pig for a period of 4-15 weeks, excised and the implant site sectioned and submitted for histological analysis. All forms of diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating compared to the silicone negative control samples. All forms of diamond exhibited similar or lower levels of acute, chronic inflammatory, and foreign body responses compared to the silicone negative control indicating that the materials are well tolerated in vivo.
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    In Vivo Feasibility of Epiretinal Stimulation Using Ultrananocrystalline Diamond 1 Electrodes
    (IOP Publishing, 2020-07) Shivdasani, Mohit; Evans, Mihailo; Burns, Owen; Yeoh, Jonathon; Allen, Penelope; Nayagam, David; Villalobos, Joel; Abbott, Carla; Luu, Chi; Opie, Nicholas; Sabu, Anu; Saunders, Alexia; McPhedran, Michelle; Cardamone, Lisa; McGowan, Ceara; Maxim, Vanessa; Williams, Richard; Fox, Kate; Cicione, Rosemary; Garrett, David; Ahnood, Arman; Ganesan, Kumaravelu; Meffin, Hamish; Burkitt, Anthony; Prawer, Steven; Williams, Chris; Shepherd, Robert
    PURPOSE: Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. METHODS: A prototype implant containing up to twenty-five 120×120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. RESULTS: The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in 8 animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in-situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. CONCLUSIONS: The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.
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    Safety and efficacy of explanting or replacing suprachoroidal electrode arrays in a feline model
    (John Wiley and Sons, 2015-04) Leung, Ronald; Nayagam, David; Williams, Richard; Allen, Penelope; Salinas-La Rosa, Cesar; Shivdasani, Mohit; Ayton, Lauren; Basa, Meri; Yeoh, Jonathan; Saunders, Alexia; Shepherd, Robert; Williams, Chris
    BACKGROUND: A key requirement for retinal prostheses is the ability for safe removal or replacement. We examined whether suprachoroidal electrode arrays can be removed or replaced after implantation. METHODS: Suprachoroidal electrode arrays were unilaterally implanted into 13 adult felines. After 1 month, arrays were surgically explanted (n = 6), replaced (n = 5) or undisturbed (n = 2). The retina was assessed periodically using fundus photography and optical coherence tomography. Three months after the initial implantation, the function of replaced or undisturbed arrays was assessed by measuring the responses of the visual cortex to retinal electrical stimulation. The histopathology of tissues surrounding the implant was examined. RESULTS: Array explantation or replacement was successful in all cases. Fundus photography showed localized disruption to the tapetum lucidum near the implant's tip in seven subjects following implantation. Although optical coherence tomography showed localized retinal changes, there were no widespread statistically significant differences in the thickness of the retinal layers or choroid. The distance between the electrodes and retina increased after device replacement but returned to control values within eight weeks (P < 0.03). Staphylomas developed near the scleral wound in five animals after device explantation. Device replacement did not alter the cortical evoked potential threshold. Histopathology showed localized outer nuclear layer thinning, tapetal disruption and pseudo-rosette formation, but the overall retinal morphology was preserved. CONCLUSIONS: It is feasible to remove or replace conformable medical grade silicone electrode arrays implanted suprachoroidally. The scleral wound requires careful closure to minimize the risk of staphylomas.
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    Safety Studies for a 44-Channel Suprachoroidal Retinal Prosthesis: A Chronic Passive Study
    (IOVS, 2018-03) Abbott, Carla; Nayagam, David; Luu, Chi; Epp, Stephanie; Williams, Richard; Salinas-LaRosa, Cesar; Villalobos, Joel; McGowan, Ceara; Shivdasani, Mohit; Burns, Owen; Leavens, Jason; Yeoh, Jonathon; Brandli, Alice; Thien, Patrick; Zhou, Jenny; Feng, Helen; Williams, Chris; Shepherd, Robert; Allen, Penelope
    Abstract Purpose: Following successful clinical outcomes of the prototype suprachoroidal retinal prosthesis, Bionic Vision Australia has developed an upgraded 44-channel suprachoroidal retinal prosthesis to provide a wider field of view and more phosphenes. The aim was to evaluate the preclinical passive safety characteristics of the upgraded electrode array. Methods: Ten normal-sighted felines were unilaterally implanted with an array containing platinum electrodes (44 stimulating and 2 returns) on a silicone carrier near the area centralis. Clinical assessments (color fundus photos, optical coherence tomography, full-field electroretinography, intraocular pressure) were performed under anesthesia prior to surgery, and longitudinally for up to 20 weeks. Histopathology grading of fibrosis and inflammation was performed in two animals at 13 to 15 weeks. Results: Eight animals showed safe electrode array insertion (good retinal health) and good conformability of the array to the retinal curvature. Eight animals demonstrated good mechanical stability of the array with only minor (<2 disc diameters) lateral movement. Four cases of surgical or stability complications occurred due to (1) bulged choroid during surgery, (2) hemorrhage from a systemic bleeding disorder, (3) infection, and (4) partial erosion of thin posterior sclera. There was no change in retinal structure or function (other than that seen at surgery) at endpoint. Histopathology showed a mild foreign body response. Electrodes were intact on electrode array removal. Conclusions: The 44-channel suprachoroidal electrode array has an acceptable passive safety profile to proceed to clinical trial. The safety profile is expected to improve in human studies, as the complications seen are specific to imitations (anatomic differences) with the feline model.
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    Techniques for Processing Eyes Implanted With a Retinal Prosthesis for Localized Histopathological Analysis.
    (JoVE Corp, 2013-02) Nayagam, David; McGowan, Ceara; Villalobos, Joel; Williams, Richard; Salinas-La Rosa, Cesar; McKelvie, Penelope; Lo, Irene; Basa, Meri; Tan, Justin; Williams, Chris
    With the recent development of retinal prostheses, it is important to develop reliable techniques for assessing the safety of these devices in preclinical studies. However, the standard fixation, preparation, and automated histology procedures are not ideal. Here we describe new procedures for evaluating the health of the retina directly adjacent to an implant. Retinal prostheses feature electrode arrays in contact with eye tissue. Previous methods have not been able to spatially localize the ocular tissue adjacent to individual electrodes within the array. In addition, standard histological processing often results in gross artifactual detachment of the retinal layers when assessing implanted eyes. Consequently, it has been difficult to assess localized damage, if present, caused by implantation and stimulation of an implanted electrode array. Therefore, we developed a method for identifying and localizing the ocular tissue adjacent to implanted electrodes using a (color-coded) dye marking scheme, and we modified an eye fixation technique to minimize artifactual retinal detachment. This method also rendered the sclera translucent, enabling localization of individual electrodes and specific parts of an implant. Finally, we used a matched control to increase the power of the histopathological assessments. In summary, this method enables reliable and efficient discrimination and assessment of the retinal cytoarchitecture in an implanted eye.
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    Techniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks
    (JoVE Corp, 2014-12) Nayagam, David; Durmo, Irfan; McGowan, Ceara; Williams, Richard; Shepherd, Robert; Bionic Vision Australia Consortia
    Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices currently entering the market. In order to evaluate the safety of these devices, in preclinical studies, reliable techniques are needed. However, the hard metal components utilised in some retinal implants are not compatible with traditional histological processes, particularly in consideration for the delicate nature of the surrounding tissue. Here we describe techniques for assessing the health of the eye directly adjacent to a retinal implant secured epiretinally with a metal tack. Retinal prostheses feature electrode arrays in contact with eye tissue. The most commonly used location for implantation is the epiretinal location (posterior chamber of the eye), where the implant is secured to the retina with a metal tack that penetrates all the layers of the eye. Previous methods have not been able to assess the proximal ocular tissue with the tack in situ, due to the inability of traditional histological techniques to cut metal objects. Consequently, it has been difficult to assess localized damage, if present, caused by tack insertion. Therefore, we developed a technique for visualizing the tissue around a retinal tack and implant. We have modified an established technique, used for processing and visualizing hard bony tissue around a cochlear implant, for the soft delicate tissues of the eye. We orientated and embedded the fixed eye tissue, including the implant and retinal tack, in epoxy resin, to stabilise and protect the structure of the sample. Embedded samples were then ground, polished, stained, and imaged under various magnifications at incremental depths through the sample. This technique allowed the reliable assessment of eye tissue integrity and cytoarchitecture adjacent to the metal tack.
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    Vagus nerve stimulation to treat inflammatory bowel disease: a chronic, preclinical safety study in sheep
    (Future Medicine, 2019-02) Payne, Sophie; Burns, Owen; Stebbing, Martin; Thomas, Ross; de Silva, Angel; Sedo, Alicia; Weissenborn, Frank; Hyakumura, Tomoko; Huynh, Mario; May, Clive; Williams, Richard; Furness, John; Fallon, James; Shepherd, Robert
    Aim: Electrical stimulation of the left cervical vagus nerve is a feasible therapy for inflammatory bowel disease (IBD). However, due to the location of the electrode placement, stimulation is often associated with side effects. Methods: We developed a cuff electrode array, designed to be implanted onto the vagus nerve of the lower thorax or abdomen, below branches to vital organs, to minimize off-target effects to stimulation. Results: Following chronic implantation and electrical stimulation, electrodes remained functional and neural thresholds stable, while there were minimal off-target affects to stimulation. No nerve damage or corrosion of stimulated electrodes was observed. Conclusion: This novel electrode array, located on the vagus nerve below branches to vital organs, is a safe approach for the treatment of inflammatory bowel disease.