Novel rat model of nonunion fracture with vascular deficit

Roberto‐Rodrigues, Mauro; Fernandes, Reinaldo; Senos, R.; Scoralick, A.C.D.; Bastos, Ana L.; Santos, Thaís Maria Pires dos; Viana, L P; Lima, I.; Guzmán-Silva, Maria Angélica; Kfoury-Júnior, J.R.

doi:10.1016/j.injury.2015.01.033

Cited by 19 publications

(14 citation statements)

References 18 publications

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“…Animal models of atrophic nonunion have focused on fractures that will not heal over the animal's lifetime, typically induced mechanically or physically. While many early studies created these models of atrophic nonunion in rabbits [30][31][32], more recent work has migrated towards rat [33][34][35][36][37] and mouse [13] models. Specifically, a recent study by Wang, L., et al [38] demonstrated a nonsurgical atrophic nonunion fracture model using radiation to induce periosteal damage.…”

Section: Discussionmentioning

confidence: 99%

“…There are many described models of atrophic nonunion in large animals and rodents created by mechanical or thermal disruption of periosteum and bone at the fracture site. (6,8,26,(42)(43)(44)(45)(46)(47)(48)(49)(50) For example, Garcia et al (26) created approximately 2 mm segmental defects with periosteal stripping in mice femora, and observed atrophic nounion after 15 weeks. A recent study by Wang et al (51) demonstrated a nonsurgical atrophic nonunion model using radiation to induce periosteal damage.…”

Section: Discussionmentioning

confidence: 99%

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Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model

Hixon

Sykes

Yoneda

et al. 2020

Preprint

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Nonunion is defined as the permanent failure of a fractured bone to heal, often necessitating surgical intervention. Atrophic nonunions are a subtype that are particularly difficult to treat. Animal models of atrophic nonunion are available; however, these require surgical or radiation induced trauma to disrupt periosteal healing. While these approaches can result in nonunion, such invasive methods are not representative of many clinical nonunions where osseous regeneration has been arrested by a “failure of biology”. We hypothesized that arresting osteoblast cell proliferation after fracture would lead to atrophic nonunion in mice. Using mice that express a thymidine kinase (tk) ‘suicide gene’ driven by the 3.6Col1a1 promoter (Col1-tk), proliferating osteoblast lineage cells can be ablated upon exposure to the nucleoside analog ganciclovir (GCV). Wild-type (WT; control) and Col1-tk littermates were subjected to a full femur fracture and intramedullary fixation at 12 weeks old. Post injury, mice were dosed with GCV twice daily for 2 or 4 weeks. Histologically, we confirmed abundant tk+ expression in fracture callus, and diminished periosteal cell proliferation in Col1-tk mice at 3 weeks post fracture. Moreover, Col1-tk mice had less osteoclast activity, mineralized callus, and vasculature at the fracture site compared to WT mice. Additional mice were monitored for 12 weeks with in vivo radiographs and microCT scans, which revealed delayed bone bridging and reduced callus size in Col1-tk mice. Following sacrifice, ex vivo microCT and histology demonstrated failed union with residual bone fragments and fibrous tissue in Col1-tk mice. Biomechanical testing demonstrated an inability to recover torsional strength in Col1-tk mice compared to WT. Our data indicates that suppression of proliferating osteoblast-lineage cells for either 2 or 4 weeks after fracture blunts the formation and remodeling of a mineralized callus leading to a functional nonunion. We propose this as a new murine model of atrophic nonunion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model

Hixon

Sykes

Yoneda

et al. 2020

Preprint

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“…O princípio físico para a formação da imagem microtomográfica baseia-se na propriedade dos materiais de atenuação dos raios X (MACHADO et al, 2014), o qual depende da composição e da densidade do material avaliado (DU PLESSIS; BOSHOFF, 2019). A microCT tem sido aplicada em diversas áreas do conhecimento, como: caracterização de materiais (HANKE et al, 2016), arqueologia (ZANOLLI et al, 2017), geologia (JACQUES et al, 2014), engenharia de tecidos (BOERCKEL et al, 2014), odontologia (DALSTRA et al, 2015) e ortopedia (ROBERTO-RODRIGUES et al, 2015).…”

Section: Introductionunclassified

Microtomografia Computadorizada: Princípios De Funcionamento E Utilização Em Amostras Biológicas

Queiroz¹,

Silva²,

Freitas³

et al. 2019

Enci Bio

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Micro-computed microtomography (microCT) is a material evaluation technique that uses the principle of X-ray attenuation for the formation of two-dimensional and three-dimensional images. This technique allows the visualization of high-resolution and three-dimensional images of small samples through the digital union of hundreds of cross-sections. In view of the increasing use of microCT, this study aims to review the basic principles of microCT operation and its use in some types of biological samples. During the review are discussed topics on historical aspects of microCT development, principles of microCT equipment operation and application of the technique in some types of biological samples such as bones, teeth, cartilage, vascular system and small rodent liver. The authors present some advantages of using microCT in research on morphology of biological tissue, which can be performed with ex vivo samples and in vivo experiments with small rodents. It is expected that the dissemination of this technique will broaden the research with microCT in biological samples in Brazil.

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“…The interaction between bone cells, inflammatory mediators and constituents of the immune system involved in bone repair, continue to be of great scientific interest to researchers and clinicians [1][2][3][4][5][6][7][8][9][10][11][12]. Investigation of the critical role of immune cells during the bone healing is ongoing.…”

Section: Introductionmentioning

confidence: 99%

The roles of immune cells in bone healing; what we know, do not know and future perspectives

El-Jawhari

Jones

Giannoudis

2016

Injury

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Novel rat model of nonunion fracture with vascular deficit

Cited by 19 publications

References 18 publications

Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model

Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model

Microtomografia Computadorizada: Princípios De Funcionamento E Utilização Em Amostras Biológicas

The roles of immune cells in bone healing; what we know, do not know and future perspectives

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