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

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.

THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING

2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
S. J. Hollister ◽  
M. B. Wheeler ◽  
S. E. Feinberg ◽  
W. L. Murphy
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Large Animal ◽  
Engineering Studies ◽  
Large Animal Models ◽  
Clinical Indications ◽  
Human Situation

The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).

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.

NOVEL BIOMIMETIC ANGIOGENIC ACELLULAR URINARY BLADDER FOR URINARY BLADDER TISSUE ENGINEERING IN SMALL AND LARGE ANIMAL MODELS

2008 ◽  
Vol 179 (4S) ◽  
pp. 75-76
Author(s):  
Jennifer Haig ◽  
Herman Yeger ◽  
Roula Antoon ◽  
Katherine Moore ◽  
Walid A Farhat
Keyword(s):  
Tissue Engineering ◽  
Animal Models ◽  
Urinary Bladder ◽  
Large Animal ◽  
Bladder Tissue ◽  
Large Animal Models

scholarly journals Use of Perfusion Bioreactors and Large Animal Models for Long Bone Tissue Engineering

2014 ◽  
Vol 20 (2) ◽  
pp. 126-146 ◽  
Author(s):  
Leandro S. Gardel ◽  
Luís A. Serra ◽  
Rui L. Reis ◽  
Manuela E. Gomes
Keyword(s):  
Tissue Engineering ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Long Bone ◽  
Large Animal ◽  
Large Animal Models ◽  
Perfusion Bioreactors

scholarly journals Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

2020 ◽  
Vol 8 ◽  
Author(s):  
Iris Ribitsch ◽  
Pedro M. Baptista ◽  
Anna Lange-Consiglio ◽  
Luca Melotti ◽  
Marco Patruno ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Animal Models ◽  
Regenerative Medicine ◽  
Large Animal ◽  
Large Animal Models

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.

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