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1.
Front Neurosci ; 15: 758427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690689

RESUMO

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees' truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE's implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE's suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question. Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart. Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 µA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve's center were, on average, half those of leads located near the periphery (54.92 µA vs. 110.71 µA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads' thresholds decreased or remained stable over the 3-week span. The remaining two leads' thresholds increased by 70-74%, possibly due to scarring or device failure. Significance: This work represents an important first step in establishing the MSE's viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

2.
J Reconstr Microsurg ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553344

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

3.
J Reconstr Microsurg ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404105

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

4.
Front Neurosci ; 15: 632768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935630

RESUMO

Background/Aims: Bioelectric nerve stimulation (eStim) is an emerging clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes. Methods: To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and lower limb, for 8 weeks in control and streptozotocin-induced type 1 diabetic (T1D) rats. Metabolic, gait, nerve and bone assessments were used to evaluate the progression of diabetes and the effect of sciatic nerve eStim on neuropathy and musculoskeletal disease, while also considering the effects of cuff placement and chronic eStim in otherwise healthy animals. Results: Rats with T1D exhibited increased mechanical allodynia in the hindpaw, reduced muscle mass, decreased cortical and cancellous bone volume fraction (BVF), reduced cortical bone tissue mineral density (TMD), and decreased bone marrow adiposity. Type 1 diabetes also had an independent effect on gait. Placement of the cuff electrode alone resulted in altered gait patterns and unilateral reductions in tibia length, cortical BVF, and bone marrow adiposity. Alterations in gait patterns were restored by eStim and tibial lengthening was favored unilaterally; however, eStim did not prevent T1D-induced changes in muscle, bone, marrow adiposity or mechanical sensitivity. Beyond this, chronic eStim resulted in an independent, bilateral reduction in cortical TMD. Conclusion: Overall, these results provide new insight into the pathogenesis of diabetic neuroskeletal disease and its regulation by eStim. Though eStim did not prevent neural or musculoskeletal complications in T1D, our results demonstrate that clinical applications of peripheral neuromodulation ought to consider the impact of device placement and eStim on long-term skeletal health in both healthy individuals and those with metabolic disease. This includes monitoring for compounded bone loss to prevent unintended consequences including decreased bone mineral density and increased fracture risk.

5.
Cureus ; 13(3): e13728, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33842107

RESUMO

Background and objective High-frequency alternating current (HFAC) can yield a rapid-acting and reversible nerve conduction block. The present study aimed to demonstrate the successful implementation of HFAC block delivery via regenerative macro-sieve electrodes (MSEs). Methods Dual-electrode assemblies in two configurations [dual macro-sieve electrode-1 (DMSE-I), DMSE-II] were fabricated from pairs of MSEs and implanted in the transected and subsequently repaired sciatic nerves of two male Lewis rats. After four months of postoperative nerve regeneration through the MSEs' transit zones, the efficacy of acute HFAC block was tested for both configurations. Frequencies ranging from 10 kHz to 42 kHz, and stimulus amplitudes with peak-to-peak voltages ranging from 2 V to 20 V were tested. Evoked muscle force measurement was used to quantify the nerve conduction block. Results HFAC stimulation delivered via DMSE assemblies obtained a complete block at frequencies of 14 to 26 kHz and stimulus amplitudes of 12 to 20 V p-p. The threshold voltage for the complete block showed an approximately linear dependence on frequency. The threshold voltage for the partial conduction block was also approximately linear. For those frequencies that displayed both partial and complete block, the partial block thresholds were consistently lower. Conclusion This study provides a proof of concept that regenerative MSEs can achieve complete and reversible conduction block via HFAC stimulation of regenerated nerve tissue. A chronically interfaced DMSE assembly may thereby facilitate the inactivation of targeted nerves in cases wherein pathologic neuronal hyperactivity is involved.

7.
Nat Commun ; 11(1): 5990, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239608

RESUMO

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.


Assuntos
Implantes Absorvíveis , Terapia por Estimulação Elétrica/instrumentação , Traumatismos dos Nervos Periféricos/terapia , Poliuretanos/química , Tecnologia sem Fio/instrumentação , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Ratos , Regeneração , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
8.
Adv Healthc Mater ; 9(16): e2000942, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32597568

RESUMO

Measurements of regional internal body temperatures can yield important information in the diagnosis of immune response-related anomalies, for precisely managing the effects of hyperthermia and hypothermia therapies and monitoring other transient body processes such as those associated with wound healing. Current approaches rely on permanent implants that require extraction surgeries after the measurements are no longer needed. Emerging classes of bioresorbable sensors eliminate the requirements for extraction, but their use of percutaneous wires for data acquisition leads to risks for infection at the suture site. As an alternative, a battery-free, wireless implantable device is reported here, which is constructed entirely with bioresorbable materials for monitoring regional internal body temperatures over clinically relevant timeframes. Ultimately, these devices disappear completely in the body through natural processes. In vivo demonstrations indicate stable operation as subcutaneous and intracranial implants in rat models for up to 4 days. Potential applications include monitoring of healing cascades associated with surgical wounds, recovery processes following internal injuries, and the progression of thermal therapies for various conditions.


Assuntos
Implantes Absorvíveis , Temperatura Corporal , Animais , Ratos , Temperatura , Tecnologia sem Fio , Cicatrização
9.
Sci Adv ; 5(7): eaaw1899, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31281889

RESUMO

Continuous measurements of pressure and temperature within the intracranial, intraocular, and intravascular spaces provide essential diagnostic information for the treatment of traumatic brain injury, glaucoma, and cardiovascular diseases, respectively. Optical sensors are attractive because of their inherent compatibility with magnetic resonance imaging (MRI). Existing implantable optical components use permanent, nonresorbable materials that must be surgically extracted after use. Bioresorbable alternatives, introduced here, bypass this requirement, thereby eliminating the costs and risks of surgeries. Here, millimeter-scale bioresorbable Fabry-Perot interferometers and two dimensional photonic crystal structures enable precise, continuous measurements of pressure and temperature. Combined mechanical and optical simulations reveal the fundamental sensing mechanisms. In vitro studies and histopathological evaluations quantify the measurement accuracies, operational lifetimes, and biocompatibility of these systems. In vivo demonstrations establish clinically relevant performance attributes. The materials, device designs, and fabrication approaches outlined here establish broad foundational capabilities for diverse classes of bioresorbable optical sensors.


Assuntos
Implantes Absorvíveis , Técnicas Biossensoriais , Pressão Intracraniana/fisiologia , Monitorização Fisiológica , Humanos , Interferometria/métodos , Imageamento por Ressonância Magnética/métodos , Dispositivos Ópticos , Fótons , Silício/química , Temperatura
10.
Nat Biomed Eng ; 3(1): 37-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932064

RESUMO

Pressures in the intracranial, intraocular and intravascular spaces are clinically useful for the diagnosis and management of traumatic brain injury, glaucoma and hypertension, respectively. Conventional devices for measuring these pressures require surgical extraction after a relevant operational time frame. Bioresorbable sensors, by contrast, eliminate this requirement, thereby minimizing the risk of infection, decreasing the costs of care and reducing distress and pain for the patient. However, the operational lifetimes of bioresorbable pressure sensors available at present fall short of many clinical needs. Here, we present materials, device structures and fabrication procedures for bioresorbable pressure sensors with lifetimes exceeding those of previous reports by at least tenfold. We demonstrate measurement accuracies that compare favourably to those of the most sophisticated clinical standards for non-resorbable devices by monitoring intracranial pressures in rats for 25 days. Assessments of the biodistribution of the constituent materials, complete blood counts, blood chemistry and magnetic resonance imaging compatibility confirm the biodegradability and clinical utility of the device. Our findings establish routes for the design and fabrication of bioresorbable pressure monitors that meet requirements for clinical use.


Assuntos
Implantes Absorvíveis , Doença Crônica , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Dióxido de Silício/química , Temperatura , Cicatrização , Animais , Feminino , Cinética , Imageamento por Ressonância Magnética , Masculino , Camundongos , Ratos Endogâmicos Lew , Distribuição Tecidual
11.
Nat Med ; 24(12): 1830-1836, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30297910

RESUMO

Peripheral nerve injuries represent a significant problem in public health, constituting 2-5% of all trauma cases1. For severe nerve injuries, even advanced forms of clinical intervention often lead to incomplete and unsatisfactory motor and/or sensory function2. Numerous studies report the potential of pharmacological approaches (for example, growth factors, immunosuppressants) to accelerate and enhance nerve regeneration in rodent models3-10. Unfortunately, few have had a positive impact in clinical practice. Direct intraoperative electrical stimulation of injured nerve tissue proximal to the site of repair has been demonstrated to enhance and accelerate functional recovery11,12, suggesting a novel nonpharmacological, bioelectric form of therapy that could complement existing surgical approaches. A significant limitation of this technique is that existing protocols are constrained to intraoperative use and limited therapeutic benefits13. Herein we introduce (i) a platform for wireless, programmable electrical peripheral nerve stimulation, built with a collection of circuit elements and substrates that are entirely bioresorbable and biocompatible, and (ii) the first reported demonstration of enhanced neuroregeneration and functional recovery in rodent models as a result of multiple episodes of electrical stimulation of injured nervous tissue.


Assuntos
Estimulação Elétrica/métodos , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Cicatrização/fisiologia , Implantes Absorvíveis/normas , Estimulação Elétrica/instrumentação , Humanos , Traumatismos dos Nervos Periféricos/fisiopatologia , Recuperação de Função Fisiológica , Tecnologia sem Fio
12.
Wounds ; 30(8): E77-E80, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30212370

RESUMO

BACKGROUND: Chronic, nonhealing wounds are a growing health care problem in the United States, affecting more than 6.5 million patients annually. OBJECTIVE: This retrospective study evaluates the clinical efficacy and utility of an implantable nanomedical scaffold in the treatment of chronic, nonhealing lower extremity wounds in patients with multiple comorbidities. MATERIALS AND METHODS: Data from patients with chronic wounds that had persisted for ≥ 4 weeks and were unresponsive to existing advanced wound care modalities were included in the study. Wounds received the implantable nanomedical scaffold weekly, or as deemed appropriate, for up to 12 weeks based on physician assessment of wound status. RESULTS: A total of 82 wounds were included in this study; wound types consisted of 34 diabetic foot ulcers, 34 venous leg ulcers, and 14 other wounds. Overall, treated wounds demonstrated progressive and sustained wound area reduction over the course of treatment, with 85% achieving complete closure at 12 weeks. CONCLUSIONS: The implantable nanomedical scaffold proved to be an effective alternative to existing wound matrices capable of supporting the natural wound healing process and may provide significant benefits as part of the treatment algorithm for challenging chronic wounds.


Assuntos
Materiais Biocompatíveis , Pé Diabético/cirurgia , Tecido de Granulação/fisiologia , Tecidos Suporte , Úlcera Varicosa/cirurgia , Cicatrização/fisiologia , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/fisiologia , Pé Diabético/complicações , Pé Diabético/fisiopatologia , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Estudos Retrospectivos , Resultado do Tratamento , Úlcera Varicosa/complicações , Úlcera Varicosa/fisiopatologia
13.
Nat Commun ; 9(1): 1690, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703901

RESUMO

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS2, including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS2-based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas.


Assuntos
Materiais Biocompatíveis/química , Técnicas Biossensoriais , Dissulfetos/química , Eletrodos Implantados , Molibdênio/química , Monitorização Fisiológica/instrumentação , Implantes Absorvíveis , Animais , Encéfalo/fisiologia , Linhagem Celular , Feminino , Fibroblastos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Monitorização Fisiológica/métodos , Ratos , Ratos Endogâmicos Lew , Temperatura
14.
Wounds ; 30(2): E21-E24, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29481335

RESUMO

OBJECTIVE: This study aims to evaluate the comparative performance of a resorbable nanofiber wound matrix (Restrata Wound Matrix; Acera Surgical Inc, St Louis, MO) and a bilayered collagen xenograft (Integra Bilayer Matrix Wound Dressing; Integra, Plainsboro, NJ) in healing critical full-thickness cutaneous wounds in a preclinical porcine model. MATERIALS AND METHODS: Full-thickness cutaneous wounds were created in Yucatan miniature swine and treated with either the nanofiber wound matrix or xenograft. Wound area was measured and inflammation and healing were assessed until euthanasia at day 15 or 30, at which time tissue samples were harvested for histopathology. RESULTS: Wounds treated with the nanofiber wound matrix demonstrated significantly faster wound areal reduction, less inflammation, greater neovascularization, more collagen maturation, and superior quality of healing compared with wounds treated with the xenograft. CONCLUSIONS: The nanofiber wound matrix is an effective wound healing material that may offer a unique alternative in the treatment of challenging refractory wounds.


Assuntos
Colágeno/metabolismo , Matriz Extracelular/patologia , Xenoenxertos/irrigação sanguínea , Reepitelização/fisiologia , Ferimentos e Lesões/patologia , Ferimentos e Lesões/terapia , Animais , Modelos Animais de Doenças , Nanofibras , Neovascularização Patológica , Pele Artificial , Suínos , Cicatrização/fisiologia
15.
J Neurosurg ; : 1-10, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29424647

RESUMO

OBJECTIVE Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery. METHODS Flexible wireless stimulators were fabricated and implanted into Lewis rats. Thin-film implants were used to deliver brief electrical stimulation (1 hour, 20 Hz) to sciatic nerves after nerve crush or nerve transection-and-repair injuries. RESULTS Electrical stimulation of injured nerves via implanted wireless stimulators significantly improved functional recovery. Brief electrical stimulation was observed to increase the rate of functional recovery after both nerve crush and nerve transection-and-repair injuries. Wireless stimulators successfully facilitated therapeutic stimulation of peripheral nerve tissue and serial assessment of nerve recovery. CONCLUSIONS Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings.

16.
J Exp Med ; 215(3): 941-961, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-29367382

RESUMO

Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct SC cytoplasmic domains, is required to establish proper myelin thickness, and facilitates organization of the myelin sheath. Furthermore, we define plectin-a scaffolding protein previously linked to SC domain organization, myelin maintenance, and a series of disorders termed "plectinopathies"-as a novel interacting partner of GPR56. Finally, we show that Gpr56 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with GPR56 mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin.


Assuntos
Bainha de Mielina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Peixe-Zebra/fisiologia , Animais , Citoesqueleto/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Mutação/genética , Bainha de Mielina/ultraestrutura , Plectina/metabolismo , Ligação Proteica , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiologia , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Transdução de Sinais , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteína rhoA de Ligação ao GTP/metabolismo
17.
J Neural Eng ; 15(2): 026009, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29192607

RESUMO

OBJECTIVE: Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). APPROACH: A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. MAIN RESULTS: Recruitment thresholds of individual regenerated fibers with diameters >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. SIGNIFICANCE: Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.


Assuntos
Axônios/fisiologia , Eletrodos Implantados , Modelos Neurológicos , Regeneração Nervosa/fisiologia , Nervos Periféricos/fisiologia , Axônios/ultraestrutura , Estimulação Elétrica/métodos , Humanos , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Mielinizadas/ultraestrutura , Tecido Nervoso/fisiologia , Nervos Periféricos/ultraestrutura
18.
Cureus ; 9(10): e1736, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-29209583

RESUMO

Wound matrix materials are used to improve the regeneration of dermal and epidermal layers in both acute and chronic wounds. Contemporary wound matrices are primarily composed of biologic materials such as processed xenogeneic and allogeneic tissues. Unfortunately, existing biologic wound matrices possess multiple limitations including poor longevity, durability, strength, and enzymatic resistance required for persistent support for new tissue formation. A fully-synthetic, resorbable electrospun material (Restrata Wound Matrix, Acera, St.Louis, Missouri ) that exhibits structural similarities to the native extracellular matrix offers a new approach to the treatment of acute and chronic wounds. This novel matrix is the first product to combine the advantages of synthetic construction (e.g. resistance to enzymatic degradation, excellent biocompatibility, strength/durability and controlled degradation) with the positive attributes of biologic materials (e.g. biomimetic architecture similar to human extracellular matrix (ECM), fibrous architecture optimized to support cellular migration and proliferation, engineered porosity to encourage tissue ingrowth and vascularization). These features allow RWM to achieve rapid and complete healing of full-thickness wounds that, in preclinical studies, is comparable to Integra Bilayer Wound Matrix (Integra LifeSciences, Plainsboro, New Jersey), a gold standard biologic material with diverse clinical indications in the wound care. Together, this review suggests that the RWM offers a unique fully-synthetic alternative to existing biologic matrices that is effective, widely available, easy to store, simple to apply and low cost.

19.
Cureus ; 9(8): e1614, 2017 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-29098126

RESUMO

A fully synthetic electrospun matrix was compared to a bi-layered xenograft in the healing of full thickness cutaneous wounds in Yucatan miniature swine. Full thickness wounds were created along the dorsum, to which these matrices were applied. The wound area was measured over the course of healing and wound tissue was scored for evidence of inflammation and healing. Animals were sacrificed at Day 15 and Day 30 and tissue samples from the wound site were harvested for histopathological analysis to evaluate inflammation and tissue healing as evidenced by granulation tissue, collagen maturation, vascularization, and epithelialization. Average wound area was significantly smaller for treatment group wounds compared to control group wounds at 15 and 30 days ([7.7 cm2 ± 0.9]/[3.8 cm2 ± 0.8]) and ([2.9 cm2 ± 1.1]/[0.2 cm2 ± 0.0]) (control/treatment) (p = 0.002/p = 0.01). Histopathological analysis of wound sections revealed superior quality of healing with treatment group wounds, as measured by inflammatory response, granulation tissue, and re-epithelialization. A fully synthetic electrospun matrix was associated with faster rates of wound closure characterized by granulation tissue, deposition of mature collagen and vascularization at earlier time points than in wounds treated with a bi-layered xenograft. Treatment with this fully synthetic material may represent a new standard of care by facilitating full-thickness wound closure while eliminating the risks of inflammatory response and disease transmission associated with biologic modalities.

20.
Neural Regen Res ; 12(6): 906-909, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28761419

RESUMO

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

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