scholarly journals Endogenous Production of n-3 Polyunsaturated Fatty Acids Promotes Fracture Healing in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yuhui Chen ◽  
He Cao ◽  
Dawei Sun ◽  
Changxin Lin ◽  
Liang Wang ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fracture Healing ◽  
Histological Analysis ◽  
Callus Formation ◽  
Healing Process ◽  
Proximal Femoral Fracture ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
X Ray

Bone fracture is a global healthcare issue for high rates of delayed healing and nonunions. Although n-3 polyunsaturated fatty acid (PUFA) is considered as a beneficial factor for bone metabolism, only few studies till date focused on the effects of n-3 PUFAs on fracture healing. In this study, we investigated the effect of endogenous n-3 PUFAs on fracture healing by measuring femur fracture repair in bothfat-1transgenic mice and WT mice. Proximal femoral fracture model was established infat-1transgenic mice and WT mice, respectively, and then the fracture was analyzed by using X-ray, micro-computed tomography (micro-CT), and histological assessment at 7, 14, 21, 28, and 35 days after fixation. The results showed that compared with WT mice,fat-1mice exhibited acceleration in fracture healing through radiographic and histological analysis (18–21 days versus 21–28 days postfracture). Meanwhile, X-ray and micro-CT analysis that showed better remodeling callus formation were in thefat-1group compared to WT group. Furthermore, histological analysis revealed that endogenous n-3 PUFAs promoted local endochondral ossification and accelerated the remodeling of calcified calluses after fracture. In conclusion, the present study indicated that endogenously produced n-3 PUFAs promote fracture healing process and accelerate bone remodeling in mice, and supplementation of n-3 PUFAs was positively associated with fracture healing.

scholarly journals Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Ariane C Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinalin vivomicro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups.The established longitudinalin vivomicro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinalin vivomicro-CT for healing-phase-specific monitoring of fracture repair in mice.

scholarly journals Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C. Tourolle né Betts ◽  
Gisela A. Kuhn ◽  
Ariane C. Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0–6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups. The established longitudinal in vivo micro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinal in vivo micro-CT for healing-phase-specific monitoring of fracture repair in mice.

scholarly journals Review of Fracture Healing and Outcomes Assessment

2020 ◽  
Vol 3 ◽  
Author(s):  
Adam Knoximprs ◽  
Anthony McGuire ◽  
Christopher Collier ◽  
Melissa Kacena ◽  
Roman Natoli
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Healing Process ◽  
Biomechanical Testing ◽  
Fracture Repair ◽  
Long Bone ◽  
Micro Computed Tomography ◽  
Fracture Callus ◽  
Medical Interventions ◽  
Healing Assessment

Background/Objective: Long bone fractures are of the most common and costly medical traumas humans experience.  Adequate characterization of the fracture healing process and development of potential medical interventions generally involves fracture induction operations on animal models of varying treatment or genetic groups, then analyzing relative repair success via synthesis of diverse assessment methodologies.  This review discusses the procedures, relevant parameters, special considerations, and key correlations of these major methodologies of fracture repair quantification.  Methods: A literature review was conducted for articles discussing the procedures or identifying correlations between each of the major fracture healing assessment methodologies.    Results: These methodologies include biomechanical testing, which provides the most direct quantification of skeletal functionality; micro-computed tomography, which enables high resolution visualization of fracture callus architecture; histology which helps elucidate the intricate processes underlying fracture repair; and x-ray which offers a non-invasive and clinically relevant view of fracture repair progress.  Each of these methodologies measure parameters directly correlating to restored functionality of fractured bone.  Conclusion: When appropriately integrated, synthesis of relevant parameters from each methodology of fracture repair assessment enables a comprehensive understanding of varying fracture healing outcomes and associated causalities.  Scientific/Clinical Policy Impact and Implications: This review may guide the interpretation and planning of fracture healing studies utilizing murine models. 

MAGNETIC RESONANCE RELAXATION-TIME STUDIES OF FRACTURE REPAIR IN CHICKS: A POTENTIAL METHOD FOR EVALUATION OF FRACTURE HEALING

2005 ◽  
Vol 09 (02) ◽  
pp. 85-92
Author(s):  
I. Nusem ◽  
S. Edelstein ◽  
I. Otremski
Keyword(s):  
Relaxation Time ◽  
Magnetic Resonance ◽  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Potential Method ◽  
Fracture Repair ◽  
Angular Deformation ◽  
Biomechanical Changes ◽  
Resonance Relaxation

Purpose: To investigate whether magnetic resonance relaxation-time measurements have a role in monitoring fracture healing. Methods: Magnetic resonance relaxation-time measurements were used to assess callus formation in chicks' tibiae and were correlated to the histopathologic and biomechanical changes that occur throughout the process of fracture repair. Results: The effective transverse relaxation time (T2) values recorded during fracture healing process were significantly longer (p = 0.0151) at day 14 (65.5575 ms.), compared with those recorded at days 3 (52.68 ms.) and 7 (55.4313 ms.). The T2 values distributions (a) at day 14 (0.2304) were significantly lower (p = 0.0313) compared with those recorded at days 7 (0.2721) and 10 (0.2742). Using a semiquantitative histologic evaluation, a significant increase in the amount of endosteal new bone (p = 0.048), and periosteal new bone (p = 0.008), associated with a significant decrease in the amount of old bone (p = 0.007) and cartilaginous tissue (p = 0.001) was observed. Analysis of the torque-angle curves demonstrated a low torque and a large angular deformation associated with low stiffness at 3–7 days post-fracture, and a high torque and a small angular deformation associated with high stiffness at 10–14 days post-fracture. Interpretation: Magnetic resonance relaxation-time follows the histopathologic and biomechanical changes occurring during the process of fracture repair and it may have a role as a potential method for objective estimation of fracture repair.

scholarly journals Изучение терапевтической эффективности препарата Алфлутоп на модели открытого перелома бедренной кости у крыс

2020 ◽  
Author(s):  
I.A. Kuksgauz ◽  
V.A. Kashkin ◽  
E.V. Shekunova ◽  
Ya.V. Guschin ◽  
V.G. Makarov ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Kirschner Wire ◽  
Fracture Line ◽  
Cartilaginous Tissue ◽  
Concomitant Therapy ◽  
X Ray ◽  
Histological Data ◽  
Therapy Completion

Введение. Клиническое применение гликозаминогликанов предотвращает разрушение макромолекулярных структур интерстициальной ткани и тканей суставного хряща, стимулирует процессы восстановления и обладает противовоспалительным действием. Эти эффекты синергичны и ведут к активации восстановительных процессов в тканях. Цель исследования - оценка терапевтической эффективности препарата Алфлутоп (К.О. Биотехнос С.А., Румыния) на модели открытого перелома бедренной кости у крыс. Методика. В области средней трети диафиза бедренной кости делали 2 расположенных перпендикулярно отверстия диаметром 1 мм, после чего перелом кости осуществляли вручную. Репозицию и фиксацию отломков осуществляли с помощью спиц Киршнера. Препарат (0,2 и 0,45 мл/кг) вводили внутримышечно, начиная с 1-х сут формирования патологии, на протяжении 20 сут. Эффективность препарата оценивали по особенностям формирования костной мозоли (рентгенологическое исследование) и скорости регенерации костной ткани (гистологическое исследование). Оценку проводили непосредственно после окончания терапии и через 2 нед после ее завершения. Результаты. Показано, что репаративный остеогенез был более выражен у животных, получавших препарат Алфлутоп. На фоне терапии в участке перелома возрастало число случаев перекрытия промежутка костной щели, а также статистически значимо увеличивалась площадь первичной костной мозоли. При гистологическом исследовании в участке перелома непосредственно после завершения терапии наблюдались признаки формирования хрящевой мозоли, а к исходу 2-й нед - костной мозоли с формированием костных балок, т. е. выявлялась отчетливая тенденция к активации репаративных процессов. Заключение. Использование препарата Алфлутоп в клинической практике целесообразно в качестве сопутствующей терапии при переломах костей.Aim. This study was designed to evaluate the therapeutic efficacy of Alflutop (К.О. Biotehnos С.А., Romania) using a rat model of femoral fracture. Methods. In the middle third region of the diaphysis of the femur, two perpendicular holes (diameter, 1 mm) were made, and the bone was manually broken. An intramedullary fixation was performed manually using a stainless Kirschner wire. Alflutop (0.2 and 0.45 ml/kg, i.m.) was injected into the rats daily for 20 days after the injury. The effect of Alflutop was evaluated immediately at the end of the treatment period and 2 weeks after the treatment completion using X-ray (callus formation) and histological data (bone regeneration). Results. The therapy resulted in some cases in partial bone fusion in the fracture line and significantly increased the area of cartilage callus. The most pronounced therapeutic effect was observed on day 35 of the experiment. Histological examination revealed signs of fracture healing in all experimental groups. Immediately after the therapy period, the formation of cartilage callus was observed in the fracture line. In 2 weeks after the therapy, signs of the formation of mineralized callus were noted. Along with the cartilaginous tissue, which was widely present, formation of trabecular bone and bone beams was observed. Two weeks after the therapy completion, the fracture healing process was more intensive in animals treated with Alflutop in either dose. Conclusion. The study confirmed that Alflutop can be used as a concomitant therapy for fracture healing in clinical practice.

scholarly journals Dietary Recommendations in Fracture Healing in Traditional Persian Medicine: A Historical Review of Literature

2017 ◽  
Vol 22 (3) ◽  
pp. 513-517 ◽  
Author(s):  
Seyed Mohammad Hosseini Kasnavieh ◽  
Seyed Mohammad Hasan Sadeghi ◽  
Seyed Mehdi Hosseini Khameneh ◽  
Mahmood Khodadoost ◽  
Azam Bazrafshan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Nutritive Value ◽  
Current Knowledge ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Dietary Recommendations ◽  
Positive Effects ◽  
Persian Medicine ◽  
Traditional Persian Medicine

Background. Fracture repair is a complex process. An inappropriate diet is a contributing risk factor for fracture nonunion. The aim of this study was to extract dietary recommendations for fracture healing according to traditional Persian medicine (TPM) literature. Method. The contents relevant to diets in fracture healing were selected from main textbooks in TPM like Al Qanon fi Al-teb ( The Canon). Other reference textbooks in traditional medicine were also used for a comprehensive study in this respect. Finally content analysis was used for summarizing and describing the results. Findings. Food stuffs are classified in TPM according to their nutritive value, their assimilability, and the quality of achieved chyme. Some light meals like chicken soup are recommended for the early days of fracture and high-nutrient and dense foods such as goat’s or sheep’s head and nuts are advised in following days for fracture healing acceleration and callus formation. Several recommendations are also provided for pacing the healing process. Conclusion. A comparison of Avicenna and other Persian sage’s recommended regimens with the recent evidence revealed the potential positive effects of their regimen for bone healing acceleration. It can shed light on a part of history of orthopedics and add to current knowledge about bone fracture and its management.

scholarly journals Can Optimizing the Mechanical Environment Deliver a Clinically Significant Reduction in Fracture Healing Time?

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 691
Author(s):  
Jan Barcik ◽  
Devakara R. Epari
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Callus Formation ◽  
Weight Bearing ◽  
Healing Process ◽  
Healing Time ◽  
Mechanical Environment ◽  
Clinically Significant ◽  
The Impact

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.

Dual Role of Caveolin-1 in β-Catenin Signaling During Fracture Healing Induced by Low-Intensity Pulsed Ultrasound in Rabbits

2021 ◽  
Vol 11 (2) ◽  
pp. 229-239
Author(s):  
Yun Li ◽  
Guanghua Liu ◽  
Feng Xiao ◽  
Wenqin Gu ◽  
Zhengdong Gao ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Molecular Mechanisms ◽  
Dual Role ◽  
Fracture Repair ◽  
Long Bone ◽  
Pulsed Ultrasound ◽  
Mineral Density ◽  
X Ray ◽  
Caveolin 1 ◽  
The Right

We did this research to observe the effect of LIPUS on long bone fracture repair and caveolin-1, β-catenin signaling expression in the radius defects of rabbits, to explore its possible molecular mechanisms. 24 male New Zealand rabbits with bilateral radial bone defects were divided into 4 groups randomly, n = 6. The right side had daily LIPUS exposure for 20 minutes, while the left received sham treatment. After 7, 14, 21, 28 days, respectively, fracture healing was observed by X-ray imaging and Dual Energy X-ray Absorptiometry (DXA) scan, specimens were harvested for histology, immunohistochemistry, and gene expression analysis. We found that LIPUS brought forward endochondral ossification, increased the bone callus size without changes in Bone Mineral Density (BMD). The caveolin-1 expression increased first then decreased, while the β-catenin kept growing during the process. These demonstrated that caveolin-1 participated in fracture healing accelerated by LIPUS, which was speculated to play a dual role in β-catenin signaling expression.

scholarly journals Exogenous PTH 1-34 Attenuates Impaired Fracture Healing in Endogenous PTH Deficiency Mice via Activating Indian Hedgehog Signaling Pathway and Accelerating Endochondral Ossification

2022 ◽  
Vol 9 ◽  
Author(s):  
Cheng Ma ◽  
Huan Liu ◽  
Yifan Wei ◽  
He Li ◽  
Dengshun Miao ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Signaling Pathway ◽  
Endochondral Ossification ◽  
Healing Process ◽  
Fracture Repair ◽  
Luciferase Reporter ◽  
Endochondral Bone Formation ◽  
Fracture Callus ◽  
Endochondral Bone ◽  
Bony Callus

Fracture healing is a complicated, long-term, and multistage repair process. Intermittent administration of parathyroid hormone (PTH) has been proven effective on intramembranous and endochondral bone formation during the fracture healing process, however, the mechanism is unclear. In this study, we investigated the role of exogenous PTH and endogenous PTH deficiency in bone fracture healing and explored the mechanism by using PTH knockout (PTH-/-) mice and ATDC5 cells. In a mouse femur fracture model, endogenous PTH deficiency could delay endochondral ossification whereas exogenous PTH promotes accumulation of endochondral bone, accelerates cartilaginous callus conversion to bony callus, enhances maturity of bony callus, and attenuates impaired fracture healing resulting from endogenous PTH deficiency. In fracture callus tissue, endogenous PTH deficiency could inhibit chondrocyte proliferation and differentiation whereas exogenous PTH could activate the IHH signaling pathway to accelerate endochondral ossification and rescue impaired fracture healing resulting from endogenous PTH deficiency. In vitro, exogenous PTH promotes cell proliferation by activating IHH signaling pathway on ATDC5 cells. In mechanistic studies, by using ChIP and luciferase reporter assays, we showed that PTH could phosphorylate CREB, and subsequently bind to the promoter of IHH, causing the activation of IHH gene expression. Therefore, results from this study support the concept that exogenous PTH 1-34 attenuates impaired fracture healing in endogenous PTH deficiency mice via activating the IHH pathway and accelerating endochondral ossification. Hence, the investigation of the mechanism underlying the effects of PTH treatment on fracture repair might guide the exploration of effective therapeutic targets for fracture.

scholarly journals Longitudinal in vivo micro-CT-based approach allows spatio-temporal characterization of fracture healing patterns and assessment of biomaterials in mouse femur defect models

2020 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Erica Floreani ◽  
Malavika H Nambiar ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Collagen Scaffolds ◽  
Non Union ◽  
Spatio Temporal ◽  
Large Bone

AbstractThorough preclinical evaluation of novel biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of biomaterials using collagen and BMP-2 as test materials. Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of biomaterials.This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of biomaterials.

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