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 Consequences of mitral valve prolapse on chordal tension: Ex vivo and in vivo studies in large animal models

2011 ◽  
Vol 142 (6) ◽  
pp. 1585-1587 ◽  
Author(s):  
Mathieu Granier ◽  
Morten O. Jensen ◽  
Jesper L. Honge ◽  
Alain Bel ◽  
Philippe Menasché ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Animal Models ◽  
Mitral Valve Prolapse ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Large Animal ◽  
Large Animal Models

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 Platelet-Derived Biomaterials Inhibit Nicotine-Induced Intervertebral Disc Degeneration Through Regulating IGF-1/AKT/IRS-1 Signaling Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972110453
Author(s):  
Wen-Cheng Lo ◽  
Chi-Sheng Chiou ◽  
Feng-Chou Tsai ◽  
Chun-Hao Chan ◽  
Samantha Mao ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
In Vivo Studies ◽  
Nicotine Treatment ◽  
Physiological Processes ◽  
Signaling Axis ◽  
Cellular Apoptosis ◽  
Ivd Degeneration ◽  
Dose Dependent

Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.

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.

scholarly journals Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone

2018 ◽  
Vol 24 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Banu Akar ◽  
Alexander M. Tatara ◽  
Alok Sutradhar ◽  
Hui-Yi Hsiao ◽  
Michael Miller ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Large Animal Models ◽  
Vascularized Bone

scholarly journals Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw4357 ◽  
Author(s):  
Jinqiang Wang ◽  
Jicheng Yu ◽  
Yuqi Zhang ◽  
Xudong Zhang ◽  
Anna R. Kahkoska ◽  
...  
Keyword(s):  
Animal Models ◽  
Insulin Release ◽  
Phenylboronic Acid ◽  
Insulin Delivery ◽  
Fast Response ◽  
Diabetic Mouse ◽  
Glucose Sensing ◽  
Large Animal ◽  
Large Animal Models

Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.

scholarly journals Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Marion Fusellier ◽  
Pauline Colombier ◽  
Julie Lesoeur ◽  
Samy Youl ◽  
Stéphane Madec ◽  
...  
Keyword(s):  
Animal Models ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Enzyme Treatment ◽  
In Vivo Model ◽  
Regenerative Approach ◽  
Radiation Induced ◽  
Longitudinal Comparison ◽  
Ivd Degeneration

Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos’ scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

Development of a System for Application of Dynamic Mechanical Compression on Intervertebral Discs in Organ Culture and Investigation of Load Magnitude Effects

2007 ◽  
Author(s):  
Casey L. Korecki ◽  
Jeffrey J. MacLean ◽  
James C. Iatridis
Keyword(s):  
Organ Culture ◽  
Intervertebral Discs ◽  
Small Sample ◽  
In Vivo Studies ◽  
Large Animal Model ◽  
Large Animal ◽  
In Vivo Models ◽  
Compression Loading ◽  
Dynamic Mechanical

In vivo studies on the intervertebral disc (IVD) indicate that the magnitude, frequency, and duration of applied compression loading results in alterations in mRNA expression, composition, and annulus fibrosus structure [1]. In vivo models typically use small animal models or small sample sizes that make it difficult to evaluate multiple dependent variables on the same tissue. In this study, it was considered a priority to utilize a large animal model to investigate the effects of magnitude of compression loading on interacting dependent variable measurements of disc cell viability, biosynthesis, composition, structure, and biomechanics. A bovine IVD organ culture system was used because it provides control over mechanical and chemical boundary conditions while maintaining viable cells and normal cell-matrix interactions. To date, there are no studies investigating the response of the IVD in organ culture to dynamic mechanical loading.

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.

Sign in / Sign up

Export Citation Format

Share Document