scholarly journals Animal Models of Osteochondral Defect for Testing Biomaterials

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiangbo Meng ◽  
Reihane Ziadlou ◽  
Sibylle Grad ◽  
Mauro Alini ◽  
Chunyi Wen ◽  
...  

The treatment of osteochondral defects (OCD) remains a great challenge in orthopaedics. Tissue engineering holds a good promise for regeneration of OCD. In the light of tissue engineering, it is critical to establish an appropriate animal model to evaluate the degradability, biocompatibility, and interaction of implanted biomaterials with host bone/cartilage tissues for OCD repair in vivo. Currently, model animals that are commonly deployed to create osteochondral lesions range from rats, rabbits, dogs, pigs, goats, and sheep horses to nonhuman primates. It is essential to understand the advantages and disadvantages of each animal model in terms of the accuracy and effectiveness of the experiment. Therefore, this review aims to introduce the common animal models of OCD for testing biomaterials and to discuss their applications in translational research. In addition, we have reviewed surgical protocols for establishing OCD models and biomaterials that promote osteochondral regeneration. For small animals, the non-load-bearing region such as the groove of femoral condyle is commonly chosen for testing degradation, biocompatibility, and interaction of implanted biomaterials with host tissues. For large animals, closer to clinical application, the load-bearing region (medial femoral condyle) is chosen for testing the durability and healing outcome of biomaterials. This review provides an important reference for selecting a suitable animal model for the development of new strategies for osteochondral regeneration.

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.


2021 ◽  
Vol 8 (4) ◽  
pp. 59
Author(s):  
Elisabete Nascimento-Gonçalves ◽  
Bruno A.L. Mendes ◽  
Rita Silva-Reis ◽  
Ana I. Faustino-Rocha ◽  
Adelina Gama ◽  
...  

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 713
Author(s):  
Shu Fang ◽  
Ditte Gry Ellman ◽  
Ditte Caroline Andersen

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.


2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.


Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4199
Author(s):  
Mahshid Hafezi ◽  
Saied Nouri Khorasani ◽  
Mohadeseh Zare ◽  
Rasoul Esmaeely Neisiany ◽  
Pooya Davoodi

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications.


2005 ◽  
Vol 25 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Siska Mortier ◽  
Norbert H. Lameire ◽  
An S. De Vriese

The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.


2015 ◽  
Vol 28 (2) ◽  
pp. 133-142 ◽  
Author(s):  
D. T. Reid ◽  
B. Eksteen

AbstractAssociated with the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) has become the leading liver disease in North America. Approximately 30 % of patients with NAFLD may develop non-alcoholic steatohepatitis (NASH) that can lead to cirrhosis and hepatocellular carcinoma (HCC). Frequently animal models are used to help identify underlying factors contributing to NAFLD including insulin resistance, dysregulated lipid metabolism and mitochondrial stress. However, studying the inflammatory, progressive nature of NASH in the context of obesity has proven to be a challenge in mice. Although the development of effective treatment strategies for NAFLD and NASH is gaining momentum, the field is hindered by a lack of a concise animal model that reflects the development of liver disease during obesity and the metabolic syndrome. Therefore, selecting an animal model to study NAFLD or NASH must be done carefully to ensure the optimal application. The most widely used animal models have been reviewed highlighting their advantages and disadvantages to studying NAFLD and NASH specifically in the context of obesity.


2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
S. J. Hollister ◽  
M. B. Wheeler ◽  
S. E. Feinberg ◽  
W. L. Murphy

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).


Author(s):  
Sarah ` Banu ◽  
Jaiganesh Ramamurthy

Periodontal diseases require treatment at an early stage to prevent further damage and aggravation of the disease. The most commonly seen periodontal diseases are gingivitis and periodontitis. Animals have contributed a major role in studying the different periodontal diseases and providing a proper treatment. Periodontal diseases are either induced in these experimental animal models or can be seen naturally. Different drugs are tested on the animals induced by the disease to find the most effective treatment for that particular disease. Different animals such as mice, rats, pigs, rabbits, hamsters, and rodents are used for the periodontal research. Different animals show a different reaction while some animals show no reaction. Each animal has its own advantages and disadvantages. The use of large animals brings a limitation in the due to its housing difficulties. Animals for periodontal research are chosen depending on their similarity with that of human anatomy and physiology. The use of these animals will help to replicate the disease seen in humans in a better and more accurate way. This will improve the treatment outcome and the prognosis of the disease. The drugs used can, hence, give a better idea about the effect it would have on the human body depending on the effects it shows on the animal models. Hence, the use of appropriate animals for the periodontal research is important to design a better treatment for these diseases. Hence, animal models play an important role in the periodontal research.


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