The development of electronics capable of interfacing with the nervous system is a rapidly advancing field with applications in basic science and clinical translation. Devices containing arrays of ...electrodes can be used in the study of cells grown in culture or can be implanted into damaged or dysfunctional tissue to restore normal function. While devices are typically designed and used exclusively for one of these two purposes, there have been increasing efforts in developing implantable electrode arrays capable of housing cultured cells, referred to as biohybrid implants. Once implanted, the cells within these implants integrate into the tissue, serving as a mediator of the electrode–tissue interface. This biological component offers unique advantages to these implant designs, providing better tissue integration and potentially long‐term stability. Herein, an overview of current research into biohybrid devices, as well as the historical background that led to their development are provided, based on the host anatomical location for which they are designed (CNS, PNS, or special senses). Finally, a summary of the key challenges of this technology and potential future research directions are presented.
Electronics capable of interfacing with the nervous system are rapidly evolving. Biohybrid implants represent a new type of neural interface, combining implantable electrodes technology and cell transplantation. An overview of biohybrid interfaces, with a classification based on the host anatomical location is provided. A summary of the key challenges and the potential future research directions are also presented.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor ...is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics.
X‐Ray Markers for Thin Film Implants Woodington, Ben J.; Coles, Lawrence; Rochford, Amy E. ...
Advanced healthcare materials,
09/2022, Volume:
11, Issue:
18
Journal Article
Peer reviewed
Open access
Implantable electronic medical devices are used in functional mapping of the brain before surgery and to deliver neuromodulation for the treatment of neurological and neuropsychiatric disorders. ...Their electrode arrays are assembled by hand, and this leads to bulky form factors with limited flexibility and low electrode counts. Thin film implants, made using microfabrication techniques, are emerging as an attractive alternative, as they offer dramatically improved conformability and enable high density recording and stimulation. A major limitation of these devices, however, is that they are invisible to fluoroscopy, the most common method used to monitor the insertion of implantable electrodes. Here, the development of mechanically flexible X‐ray markers using bismuth‐ and barium‐infused elastomers is reported. Their X‐ray attenuation properties in human cadavers are explored and it is shown that they are biocompatible in cell cultures. It is further shown that they do not distort magnetic resonance imaging images and their integration with thin film implants is demonstrated. This work removes a key barrier for the adoption of thin film implants in brain mapping and in neuromodulation.
The development of flexible X‐ray markers using bismuth and barium‐infused elastomers and their integration with thin‐film bioelectronic implants is presented. This work removes a key barrier for the adoption of thin film implants in brain mapping and in neuromodulation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce ...OSA severity.
To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA.
Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP).
Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI).
HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement.
HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms.
NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea.
NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.
Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of ...prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life.
Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined.
Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested.
Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Key points
Protective reflexes in the throat area (upper airway) are crucial for breathing.
Impairment of these reflexes can cause breathing problems during sleep such as obstructive sleep apnoea ...(OSA).
OSA is very common in people with spinal cord injury for unknown reasons.
This study shows major changes in protective reflexes that serve to keep the upper airway open in response to suction pressures in people with tetraplegia and OSA.
These results help us understand why OSA is so common in people with tetraplegia and provide new insight into how protective upper airway reflexes work more broadly.
More than 60% of people with tetraplegia have obstructive sleep apnoea (OSA). However, the specific causes are unknown. Genioglossus, the largest upper‐airway dilator muscle, is important in maintaining upper‐airway patency. Impaired genioglossus muscle function following spinal cord injury may contribute to OSA. This study aimed to determine if genioglossus reflex responses to negative upper‐airway pressure are altered in people with OSA and tetraplegia compared to non‐neurologically impaired able‐bodied individuals with OSA. Genioglossus reflex responses measured via intramuscular electrodes to ∼60 brief (250 ms) pulses of negative upper‐airway pressure (∼−15 cmH2O at the mask) were compared between 13 participants (2 females) with tetraplegia plus OSA and 9 able‐bodied controls (2 females) matched for age and OSA severity. The initial short‐latency excitatory reflex response was absent in 6/13 people with tetraplegia and 1/9 controls. Genioglossus reflex inhibition in the absence of excitation was observed in three people with tetraplegia and none of the controls. When the excitatory response was present, it was significantly delayed in the tetraplegia group compared to able‐bodied controls: excitation onset latency (mean ± SD) was 32 ± 16 vs. 18 ± 9 ms, P = 0.045; peak excitation latency was 48 ± 17 vs. 33 ± 8 ms, P = 0.038. However, when present, amplitude of the excitation response was not different between groups, 195 ± 26 vs. 219 ± 98% at baseline, P = 0.55. There are major differences in genioglossus reflex morphology and timing in response to rapid changes in airway pressure in people with tetraplegia and OSA. Altered genioglossus function may contribute to the increased risk of OSA in people with tetraplegia. The precise mechanisms mediating these differences are unknown.
Key points
Protective reflexes in the throat area (upper airway) are crucial for breathing.
Impairment of these reflexes can cause breathing problems during sleep such as obstructive sleep apnoea (OSA).
OSA is very common in people with spinal cord injury for unknown reasons.
This study shows major changes in protective reflexes that serve to keep the upper airway open in response to suction pressures in people with tetraplegia and OSA.
These results help us understand why OSA is so common in people with tetraplegia and provide new insight into how protective upper airway reflexes work more broadly.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Burmese pythons (
Python molurus bivittatus
) are native to southeastern Asia, however, there is an established invasive population inhabiting much of southern Florida throughout the Greater ...Everglades Ecosystem. Pythons have severely impacted native species and ecosystems in Florida and represent one of the most intractable invasive-species management issues across the globe. The difficulty stems from a unique combination of inaccessible habitat and the cryptic and resilient nature of pythons that thrive in the subtropical environment of southern Florida, rendering them extremely challenging to detect. Here we provide a comprehensive review and synthesis of the science relevant to managing invasive Burmese pythons. We describe existing control tools and review challenges to productive research, identifying key knowledge gaps that would improve future research and decision making for python control.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Highlights • Sensory detection of threshold intensity resistive loads in severe obstructive sleep. • apnoea. • Negative airway pressure detection was studied in obstructive sleep apnoea (OSA). • ...Sensory detection was measured using respiratory related evoked potentials (RREP). • There was reduced sensitivity for eliciting the P1 component in OSA vs. controls. • This reduction was abolished after accounting for background respiratory load. • Results suggest a mechanosensory deficit does not contribute to OSA pathogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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