scholarly journals Image-Based Radiodensity Profilometry Measures Early Remodeling at the Bone-Callus Interface in Sheep

2021 ◽  
Author(s):  
Tianyi Ren
Keyword(s):  
Bone Healing ◽  
Callus Formation ◽  
Early Stage ◽  
Numerical Models ◽  
Fracture Repair ◽  
Density Gradients ◽  
Intact Bone ◽  
Processing Techniques ◽  
Early Healing

Bone healing has been traditionally described as a four-phase process: inflammatory response, soft callus formation, hard callus development, and remodeling. The remodeling phase has been largely neglected in most numerical mechanoregulation models of fracture repair in favor of capturing early healing using a pre-defined callus domain. However, in vivo evidence suggests that remodeling occurs concurrently with repair and causes changes in cortical bone adjacent to callus that are typically neglected in numerical models of bone healing. The objective of this study was to use image processing techniques to quantify this early-stage remodeling in ovine osteotomies. To accomplish this, we developed a numerical method for radiodensity profilometry with optimization-based curve fitting to mathematically model the bone density gradients in the radial direction across the cortical wall and callus. After assessing data from 26 sheep, we defined a dimensionless density fitting function that revealed significant remodeling occurring in the cortical wall adjacent to callus during early healing, a 23% average reduction in density compared to intact. This fitting function is robust for modeling radial density gradients in both intact bone and fracture repair scenarios and can capture a wide variety of the healing responses. The fitting function can also be scaled easily for comparison to numerical model predictions and may be useful for validating future mechanoregulatory models of coupled fracture repair and remodeling.

scholarly journals Bioactive Factors-imprinted Scaffold Vehicles for Promoting Bone Healing: The Potential Strategies and the Confronted Challenges for Clinical Production

2020 ◽  
Vol 1 (1) ◽  
pp. 37-54
Author(s):  
Peng-Peng Xue ◽  
Jian-dong Yuan ◽  
Qing Yao ◽  
Ying-Zheng Zhao ◽  
He-Lin Xu
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bone Healing ◽  
Half Life ◽  
Wound Repair ◽  
Large Scale ◽  
Bone Repair ◽  
Callus Formation ◽  
Fracture Repair ◽  
Enzyme Degradation

Abstract Wound repair of bone is a complicated multistep process orchestrated by inflammation, angiogenesis, callus formation, and bone remodeling. Many bioactive factors (BFs) including cytokine and growth factors (GFs) have previously been reported to be involved in regulating wound healing of bone and some exogenous BFs such as bone morphogenetic proteins (BMPs) were proven to be helpful for improving bone healing. In this regard, the BFs reported for boosting bone repair were initially categorized according to their regulatory mechanisms. Thereafter, the challenges including short half-life, poor stability, and rapid enzyme degradation and deactivation for these exogenous BFs in bone healing are carefully outlined in this review. For these issues, BFs-imprinted scaffold vehicles have recently been reported to promote the stability of BFs and enhance their half-life in vivo. This review is focused on the incorporation of BFs into the modulated biomaterials with various forms of bone tissue engineering applications: firstly, rigid bone graft substitutes (BGSs) were used to imprint BFs for large scale bone defect repair; secondly, the soft sponge-like scaffold carrying BFs is discussed as filling materials for the cavity of bone defects; thirdly, various injectable vehicles including hydrogel, nanoparticles, and microspheres for the delivery of BFs were also introduced for irregular bone fracture repair. Meanwhile, the challenges for BFs-imprinted scaffold vehicles are also analyzed in this review.

scholarly journals Interactions between MSCs and Immune Cells: Implications for Bone Healing

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Tracy K. Kovach ◽  
Abhijit S. Dighe ◽  
Peter I. Lobo ◽  
Quanjun Cui
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Immune Cells ◽  
Bone Repair ◽  
Repair Process ◽  
The United States ◽  
Fracture Repair ◽  
Cell Based Therapy

It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on bothin vitroandin vivostudies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs.

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 In VivoStudy of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jingxian Zhu ◽  
Xin Zhang ◽  
Zhenxing Shao ◽  
Linghui Dai ◽  
La Li ◽  
...  
Keyword(s):  
Acl Reconstruction ◽  
Bone Healing ◽  
Early Stage ◽  
Cruciate Ligament ◽  
Nanofibrous Scaffold ◽  
Control Group ◽  
Type I ◽  
Specific Staining ◽  
Affinity Peptide

Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In thisin vivostudy, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament) in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

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 Axial Micromotion Locking Plate Construct Can Promote Faster and Stronger Bone Healing in an Ovine Osteotomy Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhihua Han ◽  
Jianhong Wu ◽  
Guoying Deng ◽  
Chun Bi ◽  
Jiandong Wang ◽  
...  
Keyword(s):  
Bone Healing ◽  
Locking Plate ◽  
Bone Fractures ◽  
Callus Formation ◽  
Axial Loading ◽  
Axial Loads ◽  
Torsional Testing ◽  
Bone Callus ◽  
Optimal Type

Fixing bone fractures with controlled axial interfragmentary micromotion improves bone healing; however, the optimal type of implant construct for this purpose is still lacking. The present study describes a novel axial micromotion locking plate (AMLP) construct that allows axial interfragmentary micromotion of 0.3 or 0.6 mm. We investigated whether the AMLP constructs enhance bone healing compared to an ordinary locking plate (LP) using an ovine osteotomy model. The stiffness of the constructs was tested under axial loading. We created a 3-mm osteotomy in the left hind leg tibia of sheep that was then stabilized with a 0.3- or 0.6-mm AMLP or LP construct (n = 6/group). Bone healing was monitored weekly by X-ray radiography starting from week 3 after surgery. At week 9, the specimens were collected and evaluated by computed tomography and torsional testing. We found that the AMLPs had a lower stiffness than the LP; in particular, the stiffness of the 0.6-mm AMLP construct was 86 and 41% lower than that of the LP construct for axial loads <200 and >200 N, respectively. In the in vivo experiments, tibial osteotomies treated with the 0.6-mm AMLP construct showed the earliest maximum callus formation (week 5) and the highest volume of bone callus (9.395 ± 1.561 cm3 at week 9). Specimens from this group also withstood a 27% greater torque until failure than those from the LP group (P = 0.0386), with 53% more energy required to induce failure (P = 0.0474). These results demonstrate that AMLP constructs promote faster and stronger bone healing than an overly rigid LP construct. Moreover, better bone healing was achieved with an axial micromotion of 0.6 mm as compared to 0.3 mm.

Specific Labeling of Protein Domains with Antibody Fragments

1981 ◽  
Vol 39 ◽  
pp. 416-417
Author(s):  
U. Aebi ◽  
L.E. Buhle ◽  
W.E. Fowler
Keyword(s):  
Image Processing ◽  
Specific Protein ◽  
Antibody Fragments ◽  
Supramolecular Organization ◽  
Two Dimensional ◽  
Ordered Structures ◽  
Virus Capsids ◽  
Processing Techniques

Many important supramolecular structures such as filaments, microtubules, virus capsids and certain membrane proteins and bacterial cell walls exist as ordered polymers or two-dimensional crystalline arrays in vivo. In several instances it has been possible to induce soluble proteins to form ordered polymers or two-dimensional crystalline arrays in vitro. In both cases a combination of electron microscopy of negatively stained specimens with analog or digital image processing techniques has proven extremely useful for elucidating the molecular and supramolecular organization of the constituent proteins. However from the reconstructed stain exclusion patterns it is often difficult to identify distinct stain excluding regions with specific protein subunits. To this end it has been demonstrated that in some cases this ambiguity can be resolved by a combination of stoichiometric labeling of the ordered structures with subunit-specific antibody fragments (e.g. Fab) and image processing of the electron micrographs recorded from labeled and unlabeled structures.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

scholarly journals Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity

2021 ◽  
Vol 22 (3) ◽  
pp. 1169
Author(s):  
Yuhan Chang ◽  
Chih-Chien Hu ◽  
Ying-Yu Wu ◽  
Steve W. N. Ueng ◽  
Chih-Hsiang Chang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Healing ◽  
Bone Bridge ◽  
Cell Wall Components ◽  
Osteoclast Activity ◽  
Wall Components

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.

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