Osseosurface electronics—thin, wireless, battery-free and multimodal musculoskeletal biointerfaces

AbstractBioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years. Here we introduce a new class of wireless battery-free devices, named osseosurface electronics, which feature soft mechanics, ultra-thin form factor and miniaturized multimodal biointerfaces comprised of sensors and optoelectronics directly adhered to the surface of the bone. Potential of this fully implanted device class is demonstrated via real-time recording of bone strain, millikelvin resolution thermography and delivery of optical stimulation in freely-moving small animal models. Battery-free device architecture, direct growth to the bone via surface engineered calcium phosphate ceramic particles, demonstration of operation in deep tissue in large animal models and readout with a smartphone highlight suitable characteristics for exploratory research and utility as a diagnostic and therapeutic platform.

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Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age

Neurodegenerative Diseases ◽

10.1159/000488592 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 107-119 ◽

Cited By ~ 5

Author(s):

Daniela Vidinská ◽

Petra Vochozková ◽

Petra Šmatlíková ◽

Taras Ardan ◽

Jiří Klíma ◽

...

Keyword(s):

Animal Models ◽

Huntington Disease ◽

Small Animal ◽

Realistic Model ◽

The Body ◽

Large Animal ◽

Cell Nuclei ◽

Large Animal Models ◽

Golgi Protein ◽

Testicular Degeneration

Background: Huntington disease (HD) is an incurable neurodegenerative disease caused by the expansion of a polyglutamine sequence in a gene encoding the huntingtin (Htt) protein, which is expressed in almost all cells of the body. In addition to small animal models, new therapeutic approaches (including gene therapy) require large animal models as their large brains are a more realistic model for translational research. Objective: In this study, we describe phenotype development in transgenic minipigs (TgHD) expressing the N-terminal part of mutated human Htt at the age of 24 months. Methods: TgHD and wild-type littermates were compared. Western blot analysis and subcellular fractionation of different tissues was used to determine the fragmentation of Htt. Immunohistochemistry and optical analysis of coronal sections measuring aggregates, Htt expression, neuroinflammation, and myelination was applied. Furthermore, the expression of Golgi protein acyl-CoA binding domain containing 3 (ACBD3) was analyzed. Results: We found age-correlated Htt fragmentation in the brain. Among various tissues studied, the testes displayed the highest fragmentation, with Htt fragments detectable even in cell nuclei. Also, Golgi protein ACBD3 was upregulated in testes, which is in agreement with previously reported testicular degeneration in TgHD minipigs. Nevertheless, the TgHD-specific mutated Htt fragments were also present in the cytoplasm of striatum and cortex cells. Moreover, microglial cells were activated and myelination was slightly decreased, suggesting the development of a premanifest stage of neurodegeneration in TgHD minipigs. Conclusions: The gradual development of a neurodegenerative phenotype, accompanied with testicular degeneration, is observed in 24- month-old TgHD minipigs.

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Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0022 ◽

2017 ◽

Vol 28 (1) ◽

pp. 31-43 ◽

Cited By ~ 12

Author(s):

Lan Huang ◽

Fengyan Zhao ◽

Yi Qu ◽

Li Zhang ◽

Yan Wang ◽

...

Keyword(s):

Animal Models ◽

Small Animal ◽

Underlying Disease ◽

Therapeutic Interventions ◽

Hypoxic Ischemic Encephalopathy ◽

Large Animal ◽

Large Animal Models ◽

Neurological Research ◽

Serious Disease ◽

Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

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Intratracheal aerosolization of viral vectors to newborn pig airways

BioTechniques ◽

10.2144/btn-2019-0150 ◽

2020 ◽

Vol 68 (5) ◽

pp. 235-239

Author(s):

Ashley L Cooney ◽

Patrick L Sinn

Keyword(s):

Gene Therapy ◽

Animal Models ◽

Endotracheal Tube ◽

Viral Vectors ◽

Small Animal ◽

Large Animal ◽

Large Animal Models ◽

Airway Diseases ◽

Efficient Delivery ◽

Large Animals

Gene therapy for airway diseases requires efficient delivery of nucleic acids to the airways. In small animal models, gene delivery reagents are commonly delivered as a bolus dose. However, large animal models are often more relevant for the transition from preclinical studies to human trials. Aerosolizing viral vectors to the lungs of large animals can maximize anatomical distribution. Here, we describe a technique for aerosolization of viral vectors to the airways of newborn pigs. Briefly, a pig is anesthetized and intubated with an endotracheal tube, and a microsprayer is passed through the endotracheal tube. A fine mist is then sprayed into the distal trachea. Widespread and uniform distribution of transgene expression is critical for developing successful lung gene therapy treatments.

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The Representative Porcine Model for Human Cardiovascular Disease

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/195483 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 40

Author(s):

Yoriyasu Suzuki ◽

Alan C. Yeung ◽

Fumiaki Ikeno

Keyword(s):

Animal Models ◽

Porcine Model ◽

Small Animal ◽

Large Animal ◽

Murine Models ◽

Practical Applications ◽

Large Animal Models ◽

Small Animal Models ◽

Insight Into

To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.

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A Review of the Current Mammalian Models of Alzheimer’s Disease and Challenges That Need to Be Overcome

International Journal of Molecular Sciences ◽

10.3390/ijms222313168 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13168

Author(s):

Natasha Elizabeth Mckean ◽

Renee Robyn Handley ◽

Russell Grant Snell

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Models ◽

Mouse Model ◽

Mouse Models ◽

Small Animal ◽

Large Animal ◽

Complex Disorders ◽

Large Animal Models ◽

The Impact

Alzheimer’s disease (AD) is one of the looming health crises of the near future. Increasing lifespans and better medical treatment for other conditions mean that the prevalence of this disease is expected to triple by 2050. The impact of AD includes both the large toll on individuals and their families as well as a large financial cost to society. So far, we have no way to prevent, slow, or cure the disease. Current medications can only alleviate some of the symptoms temporarily. Many animal models of AD have been created, with the first transgenic mouse model in 1995. Mouse models have been beset by challenges, and no mouse model fully captures the symptomatology of AD without multiple genetic mutations and/or transgenes, some of which have never been implicated in human AD. Over 25 years later, many mouse models have been given an AD-like disease and then ‘cured’ in the lab, only for the treatments to fail in clinical trials. This review argues that small animal models are insufficient for modelling complex disorders such as AD. In order to find effective treatments for AD, we need to create large animal models with brains and lifespan that are closer to humans, and underlying genetics that already predispose them to AD-like phenotypes.

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Premature guinea pigs: a new paradigm to investigate the late-effects of preterm birth

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000592 ◽

2014 ◽

Vol 6 (2) ◽

pp. 143-148 ◽

Cited By ~ 6

Author(s):

M. Berry ◽

C. Gray ◽

K. Wright ◽

R. Dyson ◽

I. Wright

Keyword(s):

Preterm Birth ◽

Animal Models ◽

Guinea Pigs ◽

Small Animal ◽

Large Animal ◽

New Paradigm ◽

Short Term ◽

Human Infants ◽

Caesarean Birth ◽

Large Animal Models

Preterm birth is common and the associated short-term morbidity well described. The adult-onset consequences of preterm birth are less clear, but cardiovascular and metabolic health may be adversely affected. Although large animal models of preterm birth addressing important short-term issues exist, long-term studies are hampered by significant logistical constraints. Current small animal models of prematurity require terminal caesarean section of the mother; both caesarean birth and early maternal care modify offspring adult cardio-metabolic function.We describe a novel method for inducing preterm labour in guinea pigs. With support comparable to that received by moderately preterm human infants, preterm pups are viable. Growth trajectories between preterm and term-born pups differ significantly; between term equivalent age and weaning ex-preterm animals demonstrate increased weight and ponderal index.We believe this novel paradigm will significantly improve our ability to investigate the cardio-metabolic sequelae of preterm birth throughout the life course and into the second generation.

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Cardiac metabolic imaging using hyperpolarized [1-13C]lactate as a substrate

10.1101/2020.12.04.412296 ◽

2020 ◽

Author(s):

Angus Z Lau ◽

Albert P Chen ◽

Charles H Cunningham

Keyword(s):

Animal Models ◽

Small Animal ◽

Cardiac Metabolism ◽

Metabolic Imaging ◽

Attractive Alternative ◽

Similar Degree ◽

Large Animal ◽

Large Animal Models ◽

Similar Appearance

AbstractHyperpolarized [1-13C]lactate is an attractive alternative to [1-13C]pyruvate as a substrate to investigate cardiac metabolism in vivo; it can be administered safely at a higher dose and can be polarized to a similar degree as pyruvate via dynamic nuclear polarization. While 13C cardiac experiments using HP lactate have been performed in small animal models, it has not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods used in the first human HP 13C cardiac study, 13C metabolic images were acquired following injections of HP [1-13C]lactate in porcine hearts. Data were also acquired using HP [1-13C]pyruvate for comparison. The 13C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No 13C pyruvate signal was detected in the experiments following injection of hyperpolarized 13C lactate. The SNR of injected lactate was 88 +/-14% of the SNR of injected pyruvate, and the SNR of bicarbonate in the experiments using lactate as the substrate was 52+/-19% of the SNR in the experiments using pyruvate as the substrate. The lower SNR was likely due to the shorter T1 of [1-13C]lactate as compared to [1-13C]pyruvate and the additional enzyme-catalyzed metabolic conversion step before the 13C nuclei from [1-13C]lactate were detected as 13C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart was demonstrated.

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Genetically modified large animal models for investigating neurodegenerative diseases

Cell & Bioscience ◽

10.1186/s13578-021-00729-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Weili Yang ◽

Xiusheng Chen ◽

Shihua Li ◽

Xiao-Jiang Li

Keyword(s):

Animal Models ◽

Neurodegenerative Diseases ◽

Genetically Modified ◽

Small Animal ◽

Large Animal ◽

Pathological Features ◽

Large Animal Models ◽

Progressive Degeneration ◽

Large Animals ◽

Lateral Sclerosis

AbstractNeurodegenerative diseases represent a large group of neurological disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease. Although this group of diseases show heterogeneous clinical and pathological phenotypes, they share important pathological features characterized by the age-dependent and progressive degeneration of nerve cells that is caused by the accumulation of misfolded proteins. The association of genetic mutations with neurodegeneration diseases has enabled the establishment of various types of animal models that mimic genetic defects and have provided important insights into the pathogenesis. However, most of genetically modified rodent models lack the overt and selective neurodegeneration seen in the patient brains, making it difficult to use the small animal models to validate the effective treatment on neurodegeneration. Recent studies of pig and monkey models suggest that large animals can more faithfully recapitulate pathological features of neurodegenerative diseases. In this review, we discuss the important differences in animal models for modeling pathological features of neurodegenerative diseases, aiming to assist the use of animal models to better understand the pathogenesis and to develop effective therapeutic strategies.

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Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Current HIV Research ◽

10.2174/1570162x18666191223114019 ◽

2020 ◽

Vol 18 (1) ◽

pp. 19-28 ◽

Cited By ~ 3

Author(s):

Ramesh Akkina ◽

Daniel L. Barber ◽

Moses T. Bility ◽

Karl-Dimiter Bissig ◽

Benjamin J. Burwitz ◽

...

Keyword(s):

Animal Models ◽

Hepatitis B ◽

Complex Dynamics ◽

Small Animal ◽

Large Animal ◽

Hepatitis Viruses ◽

Large Animal Models ◽

Immunodeficiency Virus ◽

Small Animal Models

The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

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The Utility of Animal Models in the Preclinical Study of Interventions to Prevent Human Coronary Artery Restenosis: Analysis and Recommendations

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614578 ◽

1999 ◽

Vol 81 (05) ◽

pp. 835-843. ◽

Cited By ~ 72

Author(s):

T. R. Griggs ◽

L. Badimon ◽

G. J. Johnson

Keyword(s):

Animal Models ◽

Animal Studies ◽

Small Animal ◽

Preclinical Study ◽

Large Animal ◽

Human Coronary Artery ◽

Large Animal Models ◽

Luminal Narrowing ◽

Small Animal Models ◽

Large Animals

SummarySmall animal models have several advantageous characteristics, but those used in preclinical restenosis research have lacked efficacy in predicting the success of interventions to inhibit restenosis in humans.Large animal models have been more successful than small animal models in predicting efficacy of interventions to inhibit restenosis in humans, but the results of studies carried out with these models have not been uniformly predictive.Confirmation of the results of small animal studies in large animals has not always yielded information predictive of success in humans; however, the absence of such confirmation has had strong negative predictive value.Small animal models used for evaluation of interventions to inhibit luminal narrowing following arterial instrumentation have failed to closely simulate human atherosclerosis and the stenotic lesions subjected to instrumentation in humans.Transgenic, atherosclerotic animals hold promise for the development of more useful small animal models to study mechanisms of the response of diseased arteries to angioplasty and stents.The pig has been the most useful large animal to study stenosis/ restenosis, but more information is needed to overcome the limitations of this model.

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