Dynamic <i>in vivo</i> monitoring of fracture healing process in response to magnesium implant with multimodal imaging: pilot longitudinal study in a rat external fixation model

Sun, Yu; Helmholz, Heike; Will, Olga; Damm, Timo; Wiese, Björn; Luczak, Monika; Peschke, Eva; Luthringer-Feyerabend, Bérengère; Ebel, Thomas; Hövener, Jan‐Bernd; Glüer, Claus C.; Willumeit‐Römer, Regine

doi:10.1039/d2bm00051b

Cited by 16 publications

(7 citation statements)

References 68 publications

(119 reference statements)

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“…The samples used in this study were obtained from preclinical research for establishing a femoral fracture model in male Sprague–Dawley rats. The experimental protocol was applied via the local authority (Ministry for Energy Transition, Agriculture, Environment, Nature and Digitalization, Schleswig-Holstein, Germany, application number: V242-30912/2020), with surgical and related details described in a previous publication [ 1 ]. The rats (20 weeks, 515−580 g) were euthanized via overdose anesthesia at post-operative week 12 after femur fractures stabilized by external fixation.…”

Section: Methodsmentioning

confidence: 99%

“…Non-invasive imaging techniques such as plain film, micro-CT, ultrasonography and magnetic resonance imaging have been successfully introduced in preclinical studies, enabling longitudinal in vivo monitoring of disease progression and treatment effects in musculoskeletal disorders [ 1 , 2 ]. However, traditional ex vivo histo-pathological methods based on microscopy remain essential for translational research, allowing high-resolution rendering of tissue and cellular details, as well as quantitative assays at the gene and protein levels [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Multicolor Histochemical Staining for Identification of Mineralized and Non-Mineralized Musculoskeletal Tissue: Immunohistochemical and Radiological Validation in Decalcified Bone Samples

2022

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Histochemical staining of paraffin-embedded decalcified bone samples is commonly used in preclinical research of musculoskeletal diseases, enabling the visualization of multiple tissue components by the application of chromogens. The purpose of this study was to introduce a novel multicolor staining protocol involving optimized chemical reagents and procedure, allowing the identification of high-mineralized bone, low-mineralized fracture callus, cartilage and skeletal muscle fibers simultaneously. Fractured femur and healthy tail vertebra samples from adult male Sprague–Dawley rats were decalcified with EDTA and formic acid, respectively, followed by paraffin embedding, tissue sectioning and multicolor staining. Conventional Movat’s pentachrome and safranin O / fast green staining were conducted in parallel for comparison. Immunohistochemical staining of collagen type-X and micro-CT analysis were included to further validate the efficacy of the staining method. The multicolor staining allowed visualization of major musculoskeletal tissue components in both types of decalcified samples, providing quality outcomes with fewer chemical reagents and simplified procedures. Immunohistochemical staining demonstrated its capacity for identification of the endochondral ossification process during fracture healing. Micro-CT imaging validated the staining outcome for high-mineralized skeletal tissue. The application of the multicolor staining may facilitate future preclinical research involving decalcified paraffin-embedded samples.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multicolor Histochemical Staining for Identification of Mineralized and Non-Mineralized Musculoskeletal Tissue: Immunohistochemical and Radiological Validation in Decalcified Bone Samples

2022

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“…Finally, some concerns have been raised through the years that pneumarthrosis can be induced as a result of hydrogen production during the corrosion process [ 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. As such, the synovial membrane can be furthermore damaged as a secondary effect to hydrogen accumulation [ 32 , 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

In Vivo Study of Local and Systemic Responses to Clinical Use of Mg–1Ca Bioresorbable Orthopedic Implants

et al. 2022

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(1) Background: Resorbable Mg-based implants represent a new direction in orthopedic surgery but have some drawbacks, such as their rapid biodegradation and increased rate of corrosion. Some in vitro studies hypothesized that tissue necrosis, incision dehiscence, risk of gas embolization in vital organs, interference with coagulation processes, and trophocyte viability impairment can occur. (2) Methods: We conducted an in vivo study on ten rabbit cases, in two groups; group one, consisting of six cases, received cylindrical implants of Mg–1Ca alloy in tibial intramedullary bone tissue. Group two, consisting of four cases, received Mg–1Ca parallelepiped implants, in the thigh muscular tissue. We recorded and compared weight (preoperatively and at 2, 4, and 6 weeks postoperatively), complete blood count, serum electrolytes, liver and kidney functional markers, and coagulation parameters, prior to and at 6 weeks after surgery. Local evolution was assessed radiologically and with tissue biopsies with complete pathology analysis. (3) Results: All biological markers and clinical evolution were favorable, showing good integration of the implants with none of the local or systemic signs of degradation. (4) Conclusions: Our study shows that the clinical use of Mg–1Ca bioresorbable alloys can be safe as none of the cited local or systemic complications have been identified.

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“…The radiological data was obtained with whole femur samples from a previous study involving Sprague-Dawley (SD) rats. The experimental protocols were applied via local authority (Ministry for Energy Transition, Agriculture, Environment, Nature and Digitalization, Schleswig-Holstein, Germany, application number: V242-30912/2020 and V242-6462/2021) [ 10 ]. An ex vivo scan of the bone samples was performed using a VivaCT 80 scanner (Scanco Medical AG, Brüttisellen, Switzerland) at a voltage of 70 kVp, with a beam current of 114 μA and isotropic voxel size of 39 μm.…”

Section: Methodsmentioning

confidence: 99%

“…Historically, large animals were preferred for experiments, considering the application of surgical instruments with the same dimensions for human surgeries and thus better simulating the disease treatment process [ 6 ]. In recent years, with the development of fine surgical instruments and the application of multimodal high-resolution imaging techniques, the translational potential of the bone defect model in the rat femur has been markedly enhanced, facilitating the development of biomaterials [ 7 , 8 , 9 , 10 ]. Moreover, rat femoral defect models allow the introduction of complex comorbidities such as osteoporosis, diabetes, and infection at weight-bearing sites, providing superior simulation of clinical situations than calvarial defect models [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Surgical Classification for Preclinical Rat Femoral Bone Defect Model: Standardization Based on Systematic Review, Anatomical Analysis and Virtual Surgery

2022

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Though surgical techniques profoundly influence in vivo experiments, significant heterogeneity exists in current surgeries for inducing rat femoral bone defects. Such variations reduce the reproducibility and comparability of preclinical studies, and are detrimental to clinical translation. The purposes of this study were: (1) to conduct a systematic review of rat femoral defect models, summarizing and analyzing the surgical techniques; (2) to analyze surgical design and potential pitfalls via 3D anatomy and virtual surgeries for fostering future precision research; and (3) to establish a surgical classification system, for improving the reproducibility and comparability among studies, avoiding unnecessary repetitive experiments. The online database PubMed was searched to identify studies from January 2000 to June 2022 using keywords, including rat, femur, bone defect. Eligible publications were included for a review of surgical methods. Anatomical analysis and virtual surgeries were conducted based on micro-CT reconstruction of the rat femur for further investigation and establishment of a classification system. A total of 545 publications were included, revealing marked heterogeneity in surgical methods. Four major surgical designs were reported for inducing defects from the proximal to distal femur: bone tunnel, cortical window, segmental defect, and wedge-shaped defect. Anatomical analysis revealed potential pitfalls hindering efficient clinical translation. A classification system was established according to the anatomical region, surgical design, and fixation devices. This systematic review in combination with 3D analysis and virtual surgery provides a general overview of current surgical approaches to inducing femoral defects in rats, and establishes a surgical classification facilitating preclinical research of quality and translational value.

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Dynamic in vivo monitoring of fracture healing process in response to magnesium implant with multimodal imaging: pilot longitudinal study in a rat external fixation model

Abstract: Rodent models are commonly used in pre-clinical research of magnesium (Mg) -based and other types of biomaterials for fracture treatment. Most studies selected unstable fixation methods, and there is a...

Cited by 16 publications

References 68 publications

Multicolor Histochemical Staining for Identification of Mineralized and Non-Mineralized Musculoskeletal Tissue: Immunohistochemical and Radiological Validation in Decalcified Bone Samples

Multicolor Histochemical Staining for Identification of Mineralized and Non-Mineralized Musculoskeletal Tissue: Immunohistochemical and Radiological Validation in Decalcified Bone Samples

In Vivo Study of Local and Systemic Responses to Clinical Use of Mg–1Ca Bioresorbable Orthopedic Implants

Surgical Classification for Preclinical Rat Femoral Bone Defect Model: Standardization Based on Systematic Review, Anatomical Analysis and Virtual Surgery

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