scholarly journals Animal models for studying metaphyseal bone fracture healing

2020 ◽  
Vol 40 ◽  
pp. 172-188
Author(s):  
M Haffner-Luntzer ◽  
◽  
A Ignatius

An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic burden for society. Osteoporotic fractures are frequently located in metaphyseal bone regions. They are often associated with healing complications, because of the reduced healing capacity of the diseased bone tissue, the poor primary stability of the fracture fixation in the fragile bone, and the high frequency of comorbidities in these patients. Therefore, osteoporotic fractures require optimised treatment strategies to ensure proper bone healing. Preclinical animal models can help understanding of the underlying mechanisms and development of new therapies. However, whereas diaphyseal fracture models are widely available, appropriate animal models for metaphyseal fracture healing are scarce, although essential for translational research. This review covers large and small animal models for metaphyseal fracture healing. General requirements for suitable animal models are presented, as well as advantages and disadvantages of the current models. Furthermore, differences and similarities between metaphyseal and diaphyseal bone fracture healing are discussed. Both large- and small-animal models are available for studying metaphyseal fracture healing, which mainly differ in fracture location and geometry as well as stabilisation techniques. Most common used fracture sites are distal femur and proximal tibia. Each model found in the literature has certain advantages and disadvantages; however, many lack standardisation resulting in a high variability or poor mimicking of the clinical situation. Therefore, further refinement ofanimal models is needed especially to study osteoporotic metaphyseal fracture healing.

Biomechanics ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 29-42
Author(s):  
Lucas Engelhardt ◽  
Frank Niemeyer ◽  
Patrik Christen ◽  
Ralph Müller ◽  
Kerstin Stock ◽  
...  

Simulating diaphyseal fracture healing via numerical models has been investigated for a long time. It is apparent from in vivo studies that metaphyseal fracture healing should follow similar biomechanical rules although the speed and healing pattern might differ. To investigate this hypothesis, a pre-existing, well-established diaphyseal fracture healing model was extended to study metaphyseal bone healing. Clinical data of distal radius fractures were compared to corresponding geometrically patient-specific fracture healing simulations. The numerical model, was able to predict a realistic fracture healing process in a wide variety of radius geometries. Endochondral and mainly intramembranous ossification was predicted in the fractured area without callus formation. The model, therefore, appears appropriate to study metaphyseal bone healing under differing mechanical conditions and metaphyseal fractures in different bones and fracture types. Nevertheless, the outlined model was conducted in a simplified rotational symmetric case. Further studies may extend the model to a three-dimensional representation to investigate complex fracture shapes. This will help to optimize clinical treatments of radial fractures, medical implant design and foster biomechanical research in metaphyseal fracture healing.


2018 ◽  
Vol 7 (1) ◽  
pp. 6-11 ◽  
Author(s):  
R. M. Y. Wong ◽  
M. H. V. Choy ◽  
M. C. M. Li ◽  
K-S. Leung ◽  
S. K-H. Chow ◽  
...  

ObjectivesThe treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.Materials and MethodsA literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted.ResultsFracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures.ConclusionFor a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article: R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6–11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Peter Nordbeck ◽  
Leoni Bönhof ◽  
Karl-Heinz Hiller ◽  
Sabine Voll ◽  
Paula Arias ◽  
...  

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.


2009 ◽  
Vol 2 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Richard D. Patten ◽  
Monica R. Hall-Porter

Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.


2018 ◽  
Vol 2 ◽  
pp. 2 ◽  
Author(s):  
Michele Obeid ◽  
Ramzy C. Khabbaz ◽  
Kelly D. Garcia ◽  
Kyle M. Schachtschneider ◽  
Ron C. Gaba

Animal models have become increasingly important in the study of hepatocellular carcinoma (HCC), as they serve as a critical bridge between laboratory-based discoveries and human clinical trials. Developing an ideal animal model for translational use is challenging, as the perfect model must be able to reproduce human disease genetically, anatomically, physiologically, and pathologically. This brief review provides an overview of the animal models currently available for translational liver cancer research, including rodent, rabbit, non-human primate, and pig models, with a focus on their respective benefits and shortcomings. While small animal models offer a solid starting point for investigation, large animal HCC models are becoming increasingly important for translation of preclinical results to clinical practice.


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