scholarly journals Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion

2020 ◽  
Vol 21 (22) ◽  
pp. 8701
Author(s):  
Tae-Young Kim ◽  
Jae-Kyung Park ◽  
Yam Prasad Aryal ◽  
Eui-Seon Lee ◽  
Sanjiv Neupane ◽  
...  
Keyword(s):  
Bone Healing ◽  
Tooth Loss ◽  
Pathological Condition ◽  
Developmental Regulation ◽  
Homeobox Gene ◽  
Osteogenic Potential ◽  
Micro Computed Tomography ◽  
Periodontal Ligament Fibroblasts ◽  
Healing Processes

In the present study, we examined the bone healing capacity of Meox2, a homeobox gene that plays essential roles in the differentiation of a range of developing tissues, and identified its putative function in palatogenesis. We applied the knocking down of Meox2 in human periodontal ligament fibroblasts to examine the osteogenic potential of Meox2. Additionally, we applied in vivo periodontitis induced experiment to reveal the possible application of Meox2 knockdown for 1 and 2 weeks in bone healing processes. We examined the detailed histomorphological changes using Masson’s trichrome staining and micro-computed tomography evaluation. Moreover, we observed the localization patterns of various signaling molecules, including α-SMA, CK14, IL-1β, and MPO to examine the altered bone healing processes. Furthermore, we investigated the process of bone formation using immunohistochemistry of Osteocalcin and Runx2. On the basis of the results, we suggest that the knocking down of Meox2 via the activation of osteoblast and modulation of inflammation would be a plausible answer for bone regeneration as a gene therapy. Additionally, we propose that the purpose-dependent selection and application of developmental regulation genes are important for the functional regeneration of specific tissues and organs, where the pathological condition of tooth loss lesion would be.

scholarly journals Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects

2020 ◽  
Vol 21 (15) ◽  
pp. 5550
Author(s):  
Chih-Chien Hu ◽  
Chih-Hsiang Chang ◽  
Yi-min Hsiao ◽  
Yuhan Chang ◽  
Ying-Yu Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Lipoteichoic Acid ◽  
Calcium Deposition ◽  
Micro Computed Tomography ◽  
Osteoclast Activation

Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties.

scholarly journals In-vivo histocompatibility and osteogenic potential of biodegradable PLDLA composites containing silica-based bioactive glass fiber

2020 ◽  
Vol 35 (1) ◽  
pp. 59-71
Author(s):  
Peng Wu ◽  
Yue Wang ◽  
Dongyuan Sun ◽  
Youran Luo ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Glass Fiber ◽  
Glass Fibers ◽  
Erector Spinae ◽  
Osteogenic Potential ◽  
Micro Computed Tomography ◽  
Positive Role ◽  
Inflammatory Reactions ◽  
Related Proteins

The purpose of this two-year study was to evaluate the histocompatibility and osteogenic properties of a composite material consisting of poly(l- co-d,l lactide) (PLDLA) and silica-based bioactive glass fibers in vivo. PLDLA and PLDLA/silica-based bioactive glass fibers pins were implanted into the erector spinae muscles and femurs of beagles. Muscle and bone tissue samples were harvested 6, 12, 16, 26, 52, 78, and 104 weeks after implantation. Histology analysis was used to assess the histocompatibility, angiogenesis, and bone-implant contact. Micro-computed tomography was used to evaluate bone formation around the pins. Immunohistochemistry and western blotting revealed the expression level of the osteogenesis-related proteins. Addition of bioactive glass was demonstrated to possess better histocompatibility and reduce the inflammatory reactions in vivo. Moreover, PLDLA/silica-based bioactive glass fibers pins were demonstrated to promote angiogenesis and increase osteogenesis-related proteins expression, and thus played a positive role in osteogenesis and osseointegration after implantation. Our findings indicated that a composite of PLDLA and silica-based bioactive glass fiber is a promising biodegradable material for clinical use.

scholarly journals Programable Active Fixator System for Systematic In Vivo Investigation of Bone Healing Processes

Sensors ◽  
2020 ◽  
Vol 21 (1) ◽  
pp. 17
Author(s):  
Jan Barcik ◽  
Manuela Ernst ◽  
Constantin E. Dlaska ◽  
Ludmil Drenchev ◽  
Stephan Zeiter ◽  
...  
Keyword(s):  
Bone Healing ◽  
Weight Bearing ◽  
Control Unit ◽  
Force Sensor ◽  
Systematic Investigation ◽  
Autonomous Operation ◽  
Double Osteotomy ◽  
Implanted Devices ◽  
Healing Processes

This manuscript introduces a programable active bone fixator system that enables systematic investigation of bone healing processes in a sheep animal model. In contrast to previous systems, this solution combines the ability to precisely control the mechanical conditions acting within a fracture with continuous monitoring of the healing progression and autonomous operation of the system throughout the experiment. The active fixator system was implemented on a double osteotomy model that shields the experimental fracture from the influence of the animal’s functional loading. A force sensor was integrated into the fixator to continuously measure stiffness of the repair tissue as an indicator for healing progression. A dedicated control unit was developed that allows programing of different loading protocols which are later executed autonomously by the active fixator. To verify the feasibility of the system, it was implanted in two sheep with different loading protocols, mimicking immediate and delayed weight-bearing, respectively. The implanted devices operated according to the programmed protocols and delivered seamless data over the whole course of the experiment. The in vivo trial confirmed the feasibility of the system. Hence, it can be applied in further preclinical studies to better understand the influence of mechanical conditions on fracture healing.

scholarly journals In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 381
Author(s):  
Hyunmin Choi ◽  
Kyu-Hyung Park ◽  
Narae Jung ◽  
June-Sung Shim ◽  
Hong-Seok Moon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Alveolar Bone ◽  
Human Mesenchymal Stem Cells ◽  
Titanium Implants ◽  
Osteogenic Potential ◽  
Induction Medium ◽  
Radiographic Analysis ◽  
New Bone Formation

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

scholarly journals Application of subject-specific adaptive mechanical loading for bone healing in a mouse tail vertebral defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angad Malhotra ◽  
Matthias Walle ◽  
Graeme R. Paul ◽  
Gisela A. Kuhn ◽  
Ralph Müller
Keyword(s):  
Mechanical Loading ◽  
Bone Defect ◽  
Bone Healing ◽  
Three Dimensional ◽  
Patient Specific ◽  
Dependent Manner ◽  
Micro Computed Tomography ◽  
Computed Tomography Images ◽  
Bone Defect Healing ◽  
Subject Specific

AbstractMethods to repair bone defects arising from trauma, resection, or disease, continue to be sought after. Cyclic mechanical loading is well established to influence bone (re)modelling activity, in which bone formation and resorption are correlated to micro-scale strain. Based on this, the application of mechanical stimulation across a bone defect could improve healing. However, if ignoring the mechanical integrity of defected bone, loading regimes have a high potential to either cause damage or be ineffective. This study explores real-time finite element (rtFE) methods that use three-dimensional structural analyses from micro-computed tomography images to estimate effective peak cyclic loads in a subject-specific and time-dependent manner. It demonstrates the concept in a cyclically loaded mouse caudal vertebral bone defect model. Using rtFE analysis combined with adaptive mechanical loading, mouse bone healing was significantly improved over non-loaded controls, with no incidence of vertebral fractures. Such rtFE-driven adaptive loading regimes demonstrated here could be relevant to clinical bone defect healing scenarios, where mechanical loading can become patient-specific and more efficacious. This is achieved by accounting for initial bone defect conditions and spatio-temporal healing, both being factors that are always unique to the patient.

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.

In Vitro Culture of Human Thyroid Cells: Preliminary Findings on the Role of the Pathological Condition of the Donors

1997 ◽  
Vol 25 (2) ◽  
pp. 153-160
Author(s):  
Francesca Mattioli ◽  
Marianna Angiola ◽  
Laura Fazzuoli ◽  
Francesco Razzetta ◽  
Antonietta Martelli
Keyword(s):  
Pathological Condition ◽  
Primary Cultures ◽  
S Phase ◽  
Human Thyroid ◽  
Thyroid Cells ◽  
Toxicological Studies ◽  
Predictive Indicator

Although primary cultures of human thyroid cells are used for endocrinological and toxicological studies, until now no attention has been paid toward verifying whether the hormonal conditions to which the gland was exposed in vivo prior to surgery could influence in vitro responses. Our findings suggest that the hormonal situation in vivo cannot be used as a predictive indicator of triiodothyronine and thyroxine release and/or S-phase frequency in vitro, either with or without the addition of bovine thyrotropin.

scholarly journals In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 946
Author(s):  
Katharina Kowalewicz ◽  
Elke Vorndran ◽  
Franziska Feichtner ◽  
Anja-Christina Waselau ◽  
Manuel Brueckner ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Bone Substitutes ◽  
Magnesium Phosphate ◽  
Degradation Behavior ◽  
Micro Computed Tomography ◽  
Calcium Magnesium ◽  
Interest In Research ◽  
In Vivo Degradation ◽  
Volume Decrease

Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4)2) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, Ø = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further.

scholarly journals OP0244 A PRECLINICAL TESTING TOOL: THE IN VITRO 3D FRACTURE GAP MODEL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 154.1-154
Author(s):  
M. Pfeiffenberger ◽  
A. Damerau ◽  
P. Hoff ◽  
A. Lang ◽  
F. Buttgereit ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Inflammatory Markers ◽  
Initial Phase ◽  
Gap Model ◽  
Osteogenic Markers ◽  
Immunosuppressed Patients ◽  
The Impact

Background:Approximately 10% of fractures lead to significant fracture healing disorders, with a tendency to further increase due to the aging population. Of note, especially immunosuppressed patients with ongoing inflammation show difficulties in the correct course of fracture healing leading to fracture healing disorders. Most notably, invading immune cells and secreted cytokines are considered to provide an inflammatory microenvironment within the fracture gap, primarily during the initial phase of fracture healing. Current research has the focus on small animal models, facing the problem of translation towards the human system. In order to improve the therapy of fracture healing disorders, we have developed a human cell-basedin vitromodel to mimic the initial phase of fracture healing adequately. This model will be used for the development of new therapeutic strategies.Objectives:Our aim is to develop anin vitro3D fracture gap model (FG model) which mimics thein vivosituation in order to provide a reliable preclinical test system for fracture healing disorders.Methods:To assemble our FG model, we co-cultivated coagulated peripheral blood and primary human mesenchymal stromal cells (MSCs) mimicking the fracture hematoma (FH model) together with a scaffold-free bone-like construct mimicking the bony part of the fracture gap for 48 h under hypoxic conditions (n=3), in order to reflect thein vivosituation after fracture most adequately. To analyze the impact of the bone-like construct on thein vitroFH model with regard to its osteogenic induction capacity, we cultivated the fracture gap models in either medium with or without osteogenic supplements. To analyze the impact of Deferoxamine (DFO, known to foster fracture healing) on the FG model, we further treated our FG models with either 250 µmol DFO or left them untreated. After incubation and subsequent preparation of the fracture hematomas, we evaluated gene expression of osteogenic (RUNX2,SPP1), angiogenic (VEGF,IL8), inflammatory markers (IL6,IL8) and markers for the adaptation towards hypoxia (LDHA,PGK1) as well as secretion of cytokines/chemokines using quantitative PCR and multiplex suspension assay, respectively.Results:We found via histology that both the fracture hematoma model and the bone-like construct had close contact during the incubation, allowing the cells to interact with each other through direct cell-cell contact, signal molecules or metabolites. Additionally, we could show that the bone-like constructs induced the upregulation of osteogenic markers (RUNX2, SPP1) within the FH models irrespective of the supplementation of osteogenic supplements. Furthermore, we observed an upregulation of hypoxia-related, angiogenic and osteogenic markers (RUNX2,SPP1) under the influence of DFO, and the downregulation of inflammatory markers (IL6,IL8) as compared to the untreated control. The latter was also confirmed on protein level (e.g. IL-6 and IL-8). Within the bone-like constructs, we observed an upregulation of angiogenic markers (RNA-expression ofVEGF,IL8), even more pronounced under the treatment of DFO.Conclusion:In summary, our findings demonstrate that our establishedin vitroFG model provides all osteogenic cues to induce the initial bone healing process, which could be enhanced by the fracture-healing promoting substance DFO. Therefore, we conclude that our model is indeed able to mimic correctly the human fracture gap situation and is therefore suitable to study the influence and efficacy of potential therapeutics for the treatment of bone healing disorders in immunosuppressed patients with ongoing inflammation.Disclosure of Interests:Moritz Pfeiffenberger: None declared, Alexandra Damerau: None declared, Paula Hoff: None declared, Annemarie Lang: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., Timo Gaber: None declared

scholarly journals In Vivo Assessment of Synthetic and Biological-Derived Calcium Phosphate-Based Coatings Fabricated by Pulsed Laser Deposition: A Review

Coatings ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 99
Author(s):  
Liviu Duta
Keyword(s):  
Calcium Phosphate ◽  
Pulsed Laser Deposition ◽  
Physical Vapor Deposition ◽  
Pulsed Laser ◽  
Laser Deposition ◽  
Current Status ◽  
Micro Computed Tomography ◽  
Electron Microscopies ◽  
In Vivo Assessment

The aim of this review is to present the state-of-the art achievements reported in the last two decades in the field of pulsed laser deposition (PLD) of biocompatible calcium phosphate (CaP)-based coatings for medical implants, with an emphasis on their in vivo biological performances. There are studies in the dedicated literature on the in vivo testing of CaP-based coatings (especially hydroxyapatite, HA) synthesized by many physical vapor deposition methods, but only a few of them addressed the PLD technique. Therefore, a brief description of the PLD technique, along with some information on the currently used substrates for the synthesis of CaP-based structures, and a short presentation of the advantages of using various animal and human implant models will be provided. For an in-depth in vivo assessment of both synthetic and biological-derived CaP-based PLD coatings, a special attention will be dedicated to the results obtained by standardized and micro-radiographies, (micro) computed tomography and histomorphometry, tomodensitometry, histology, scanning and transmission electron microscopies, and mechanical testing. One main specific result of the in vivo analyzed studies is related to the demonstrated superior osseointegration characteristics of the metallic (generally Ti) implants functionalized with CaP-based coatings when compared to simple (control) Ti ones, which are considered as the “gold standard” for implantological applications. Thus, all such important in vivo outcomes were gathered, compiled and thoroughly discussed both to clearly understand the current status of this research domain, and to be able to advance perspectives of these synthetic and biological-derived CaP coatings for future clinical applications.

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