Effect of Needle Puncture Injury on Human Intervertebral Disc Mechanics

2010 ◽  
Author(s):  
Raghu N. Natarajan ◽  
Alejandro Espinoza ◽  
Gunnar B. J. Andersson
Keyword(s):  
Animal Models ◽  
Intervertebral Disc ◽  
Lumbar Disc ◽  
Large Animal ◽  
Needle Puncture ◽  
Lumbar Intervertebral Disc ◽  
Model Studies ◽  
Large Animal Models ◽  
Need To Evaluate

Diagnosis, repair and regeneration of the disc often necessitate needle injection to the nucleus pulposus through the annulus. Discography in which a radio opaque material is injected into the nucleus and electrothermal treatment involving inserting a catheter into the disc requires disruption of the annulus through needle puncture. Annulus puncture may also be required during placement of nucleus implants. Needle puncture is also used to inject growth factors, gene and cell therapy for regeneration of the disc. In animal models, disc degeneration is induced over time by needle puncture of the annulus. The severity of the degeneration depends on the magnitude of the annulus needle puncture. One thing that is not clear is how much of the observed changes in the disc biomechanics and biochemical changes are due to nucleus treatment and how much is due to annular disruption through needle puncture. Animal model studies have shown that significant changes in disc mechanics were noticed within 1 week of needle puncture with a large-gauge needle. Another in-vitro animal study showed that biomechanical changes were observed in the disc when the ratio of needle diameter to disc height is greater than 40%. All these studies were focused on the effect of small number of needle diameters and addressed using animal cadaver models. How these needle puncture injury studies on small and large animal models can be extrapolated to human conditions is still not known. Thus there is need to evaluate effect of range of needle puncture diameters in human lumbar disc biomechanics. The purpose of this study is, with the help of a finite element models, quantify the biomechanical effect due to varying size of needle punctures in a human lumbar intervertebral disc.

scholarly journals Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 713
Author(s):  
Shu Fang ◽  
Ditte Gry Ellman ◽  
Ditte Caroline Andersen
Keyword(s):  
Animal Models ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Large Animal ◽  
Large Animal Models ◽  
Graft Outcome ◽  
Limited Success ◽  
Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

scholarly journals Adult Canine Intestinal Derived Organoids: A Novel In Vitro System for Translational Research in Comparative Gastroenterology

2018 ◽  
Author(s):  
Lawrance Chandra ◽  
Dana C Borcherding ◽  
Dawn Kingsbury ◽  
Todd Atherly ◽  
Yoko M Ambrosini ◽  
...  
Keyword(s):  
Animal Models ◽  
Translational Research ◽  
Three Dimensional ◽  
Metabolic Imaging ◽  
Large Animal ◽  
Large Animal Models ◽  
Molecular Features ◽  
Naturally Occurring

AbstractBackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.ResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.ConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.

Skeletal tissue engineering—from in vitro studies to large animal models

Biomaterials ◽  
2004 ◽  
Vol 25 (9) ◽  
pp. 1487-1495 ◽  
Author(s):  
Pieter Buma ◽  
Willem Schreurs ◽  
Nico Verdonschot
Keyword(s):  
Tissue Engineering ◽  
Animal Models ◽  
In Vitro Studies ◽  
Large Animal ◽  
Skeletal Tissue ◽  
Large Animal Models

THE HISTOLOGICAL LOCALIZATION OF FasL mRNA IN HUMAN LUMBAR DISC TISSUE

2006 ◽  
Vol 10 (02) ◽  
pp. 89-94
Author(s):  
Fagang Ye ◽  
Chunxiang Si ◽  
Yujin Qiu ◽  
Bohua Chen ◽  
Zhenhua Lu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Lumbar Disc ◽  
In Vitro Transcription ◽  
Lumbar Intervertebral Disc ◽  
Degenerative Disc ◽  
Disc Cells ◽  
One Step ◽  
Notochord Cells ◽  
Fasl Mrna

Lumbar disc has become a degenerative tissue since teenage. Apoptosis plays an important role in the processes of degeneration. FasL, a ligand of Fas receptor (a trans-membrane protein) promote signal transduction of apoptosis. In this study, fetal disc and degenerative disc from adults were examined for FasL mRNA expression. hPBMC was first treated by PHA-P, a fragment of FasL cDNA was then synthesized through one-step RT-PCR. Verified by sequencing and recombinant plasmids linearizing, the DIG-cRNA probe was synthesized by in vitro transcription. The distribution of FasL mRNA was observed on lumbar intervertebral disc specimens using in situ hybridization. FasL mRNA signals were expressed in both notochord cells and chondrocyte-like cells in the nucleus of fetal discs. In degenerative disc, the quantity of intervertebral disc cells reduced dramatically and the expression of FasL mRNA was not detected. Expression of FasL in fetal disc implied that Fas/FasL triggered cell death signal pathway involved in lumbar disk transition and degeneration.

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

2020 ◽  
Vol 18 (1) ◽  
pp. 19-28 ◽  
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.

scholarly journals Atherosclerosis and Thrombosis: Insights from Large Animal Models

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Gemma Vilahur ◽  
Teresa Padro ◽  
Lina Badimon
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Large Animal ◽  
Isolated Cells ◽  
Large Animal Models ◽  
Thrombosis Research ◽  
Human Pathology ◽  
Thrombotic Complications

Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination ofin vitro, ex vivo, andin vivoexperimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the availableatherothrombotic-likeanimal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans.

Asymmetric Loading Promotes Early Signs of Intervertebral Disc Degeneration in Large Animal Organ Culture

2009 ◽  
Author(s):  
Casey L. Korecki ◽  
Benjamin A. Walter ◽  
Karolyn E. Godburn ◽  
James C. Iatridis
Keyword(s):  
Animal Models ◽  
Intervertebral Disc ◽  
Organ Culture ◽  
Biological Response ◽  
In Vivo Studies ◽  
Large Animal ◽  
Large Animal Models ◽  
Bending Loads ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration is a complex pathology, involving alterations in mechanical and biological function. Mechanical injury to IVDs may contribute to the development of IVD degeneration, and can arise following excessive loading or repeated exposure to loading levels which are not instantaneously damaging. Lateral bending and flexion produced the highest maximum shear strains in human IVDs and are considered the motions that place the IVD at greatest risk of injury (1). The biological response of the IVD to combined bending and compression has been examined in vivo in rat and mouse tail bending models demonstrating structural disruption, apoptosis and remodeling (2,4). However, there are practical limitations to current in vivo studies, as it can be difficult to apply repeated bending loads to the disc in vivo, and few large animal models exist capable of tracking the early biological, structural and compositional changes from asymmetrical loading. IVD organ culture allows control over mechanical boundary conditions and investigation of cellular responses to loading while the IVD remains largely intact, and allows the use of large animal models which more closely mimic the nutritional and compositional nature of human IVDs.

scholarly journals HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation

2020 ◽  
Vol 21 (18) ◽  
pp. 6468
Author(s):  
Annika Mohr ◽  
Jens G. Brockmann ◽  
Felix Becker
Keyword(s):  
Animal Models ◽  
Organ Transplantation ◽  
Organ Preservation ◽  
Solid Organ Transplantation ◽  
Large Animal ◽  
Solid Organ ◽  
Large Animal Models ◽  
Htk Solution

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

scholarly journals Animal Models of Calcific Aortic Valve Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Krista L. Sider ◽  
Mark C. Blaser ◽  
Craig A. Simmons
Keyword(s):  
Animal Models ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Driving Factor ◽  
Large Animal ◽  
Calcific Aortic Valve Disease ◽  
Model Studies ◽  
Large Animal Models ◽  
Research Areas

Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

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