scholarly journals Inflammatory Profile and Osteogenic Potential of Fracture Haematoma in Humans

2019 ◽  
Vol 9 (1) ◽  
pp. 47 ◽  
Author(s):  
Ippokratis Pountos ◽  
Gavin Walters ◽  
Michalis Panteli ◽  
Thomas A. Einhorn ◽  
Peter V. Giannoudis

Fracture haematoma forms immediately after fracture and is considered essential for the bone healing process. Its molecular composition has been briefly investigated with our current understanding being based on animal studies. This study aims to analyse the inflammatory cytokine content of fracture haematoma in humans and determine its effect on osteoprogenitor cells. Twenty-three patients were recruited following informed consent. Peripheral blood, fracture haematoma and bone were collected. A Luminex assay on the levels of 34 cytokines was performed and autologous peripheral blood samples served as control. Mesenchymal Stem Cells (MSCs) were isolated following collagenase digestion and functional assays were performed. Gene expression analysis of 84 key osteogenic molecules was performed. Thirty-three inflammatory cytokines were found to be significantly raised in fracture haematoma when compared to peripheral serum (p < 0.05). Amongst the most raised molecules were IL-8, IL-11 and MMP1, -2 and -3. Fracture haematoma did not significantly affect MSC proliferation, but ALP activity and calcium deposition were significantly increased in the MSCs undergoing osteogenic differentiation. Medium supplementations with fracture haematoma resulted in a statistically significant upregulation of osteogenic genes including the EGF, FGF2 and VEGFA. This seems to be the pathway involved in the osteogenic effect of fracture haematoma on bone cells. In conclusion, fracture haematoma is found to be a medium rich in inflammatory and immunomodulatory mediators. At the same time, it contains high levels of anti-inflammatory molecules, regulates osteoclastogenesis, induces angiogenesis and the production of the extracellular matrix. It appears that fracture haematoma does not affect osteoprogenitor cells proliferation as previously thought, but induces an osteogenic phenotype.

2007 ◽  
Vol 5 (25) ◽  
pp. 899-907 ◽  
Author(s):  
M.A Wood ◽  
Y Yang ◽  
E Baas ◽  
D.O Meredith ◽  
R.G Richards ◽  
...  

A number of bone tissue engineering strategies use porous three-dimensional scaffolds in combination with bioreactor regimes. The ability to understand cell behaviour relative to strain profile will allow for the effects of mechanical conditioning in bone tissue engineering to be realized and optimized. We have designed a model system to investigate the effects of strain profile on bone cell behaviour. This simplified model has been designed with a view to providing insight into the types of strain distribution occurring across a single pore of a scaffold subjected to perfusion–compression conditioning. Local strains were calculated at the surface of the pore model using finite-element analysis. Scanning electron microscopy was used in secondary electron mode to identify cell morphology within the pore relative to local strains, while backscattered electron detection in combination with X-ray microanalysis was used to identify calcium deposition. Morphology was altered according to the level of strain experienced by bone cells, where cells subjected to compressive strains (up to 0.61%) appeared extremely rounded while those experiencing zero and tensile strain (up to 0.81%) were well spread. Osteoid mineralization was similarly shown to be dose dependent with respect to substrate strain within the pore model, with the highest level of calcium deposition identified in the intermediate zones of tension/compression.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Paulo Henrique Muleta Andrade ◽  
Eric Schmidt Rondon ◽  
Carlos Alexandre Carollo ◽  
Maria Lígia Rodrigues Macedo ◽  
Luiz Henrique Viana ◽  
...  

Topical administration of powdered shells of the land snailMegalobulimus lopesiwas evaluated in Wistar rats for their healing activity in an excision wound model. The animals were distributed into three groups—G1 (control): no therapeutic intervention; G2 (vehicle controls): Lanette cream once daily; G3 (experimental animals): treated with powdered shells. Variables investigated were: wound area contraction, angiogenic activity, morphometric data, leukocytic inflammatory infiltrate, and total leukocyte count in peripheral blood. Thermogravimetric analysis and quantification and characterization of powdered shell proteins were also performed. Wound area on days 3, 7, and 14 was smaller in G3, besides presenting wound closure on day 21 for all these animals. Topical administration of the powdered shells also led to an increased number of vessels at the wound site, higher leukocyte counts in peripheral blood, and increased leukocytic inflammatory infiltrate. The results lend support to the southern Brazilian folk use ofM. lopesipowdered shells, as shown by the enhanced secondary-intention healing achieved with their topical administration to wounds in rats. Topical administration caused inflammatory response modulation, crucial to accelerating the healing process, the chronification of which increases the risks of wound contamination by opportunistic pathogens.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Dinesh K. Patel ◽  
Yu-Ri Seo ◽  
Sayan Deb Dutta ◽  
Ok Hwan Lee ◽  
Ki-Taek Lim

Maitake (Grifola frondosa) mushroom has received an enormous amount of attention as a dietary supplement due to its high nutritional values. The particle sizes of G. frondosa mushrooms were monitored by a classifying mill. β-Glucans are the bioactive component of the mushroom, and it was revealed through Fourier transform infrared spectroscopy (FTIR), proton and carbon nuclear magnetic resonance (1H and 13C-NMR), matrix-assisted laser desorption/ionization, and time-of-flight (MALDI-TOF) spectrometry. The biocompatibility of G. frondosa particles, as well as induced osteogenesis of hMSCs, was evaluated through WST-1 assay and alizarin staining (ARS) technique, respectively. Notably, enhanced cell viability was noted in the presence of G. frondosa. Significantly improved calcium deposition has observed from hMSCs with G. frondosa, suggesting to their mineralization potential. The expression of osteogenic related gene markers was examined in the presence of G. frondosa through real-time polymerase chain reaction (qPCR) technique. The upregulation of osteogenic gene markers in the presence of G. frondosa particles was indicating their superior osteogenic potential. Besides, G. frondosa also activated the secretion of various kinds of proteins from the hMSCs indicating their potential for tissue engineering applications. Enhanced secretion of different immunoglobulins was observed in rat serum in the presence of G. frondosa, further demonstrating their therapeutic nature. Therefore, G. frondosa is effective for enhanced osteogenesis and can be utilized as a natural, edible, and osteogenic agent.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
W. Blake Martin ◽  
Renaud Sicard ◽  
Shabnam M. Namin ◽  
Timothy Ganey

Debridement of the bone surface during a surgical fusion procedure initiates an injury response promoting a healing cascade of molecular mediators released over time. Autologous grafts offer natural scaffolding to fill the bone void and to provide local bone cells. Commercial bone grafting products such as allografts, synthetic bone mineral products, etc., are used to supplement or to replace autologous grafts by supporting osteoinductivity, osteoconductivity, and osteogenesis at the surgical site. To assure osteogenic potential, preservation of allogeneic cells with cryoprotectants has been developed to allow for long-term storage and thus delivery of viable bone cells to the surgical site. Dimethyl sulfoxide (DMSO) is an intracellular cryoprotectant commonly used because it provides good viability of the cells post-thaw. However, there is known cytotoxicity reported for DMSO when cells are stored above cryogenic temperatures. For most cellular bone graft products, the cryoprotectant is incorporated with the cells into the other mineralized bone and demineralized bone components. During thawing, the DMSO may not be sufficiently removed from allograft products compared to its use in a cell suspension where removal by washing and centrifugation is available. Therefore, both the allogeneic cell types in the bone grafting product and the local cell types at the bone grafting site could be affected as cytotoxicity varies by cell type and by DMSO content according to reported studies. Overcoming cytotoxicity may be an additional challenge in the formation of bone at a wound or surgical site. Other extracellular cryoprotectants have been explored as alternatives to DMSO which preserve without entering the cell membrane, thereby providing good cellular viability post-thaw and might abrogate the cytotoxicity concerns.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.


Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3067 ◽  
Author(s):  
Zoi Terzopoulou ◽  
Diana Baciu ◽  
Eleni Gounari ◽  
Theodore Steriotis ◽  
Georgia Charalambopoulou ◽  
...  

Poly(ε-caprolactone) (PCL) is a bioresorbable synthetic polyester with numerous biomedical applications. PCL membranes show great potential in guided tissue regeneration because they are biocompatible, occlusive and space maintaining, but lack osteoconductivity. Therefore, two different types of mesoporous bioactive glasses (SiO2-CaO-P2O5 and SiO2-SrO-P2O5) were synthesized and incorporated in PCL thin membranes by spin coating. To enhance the osteogenic effect of resulting membranes, the bioglasses were loaded with the bisphosphonate drug ibandronate prior to their incorporation in the polymeric matrix. The effect of the composition of the bioglasses as well as the presence of absorbed ibandronate on the physicochemical, cell attachment and differentiation properties of the PCL membranes was evaluated. Both fillers led to a decrease of the crystallinity of PCL, along with an increase in its hydrophilicity and a noticeable increase in its bioactivity. Bioactivity was further increased in the presence of a Sr substituted bioglass loaded with ibandronate. The membranes exhibited excellent biocompatibility upon estimation of their cytotoxicity on Wharton’s Jelly Mesenchymal Stromal Cells (WJ-SCs), while they presented higher osteogenic potential in comparison with neat PCL after WJ-SCs induced differentiation towards bone cells, which was enhanced by a possible synergistic effect of Sr and ibandronate.


Author(s):  
Sok Kuan Wong ◽  
Kok-Yong Chin ◽  
Soelaiman Ima-Nirwana

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.


2006 ◽  
Vol 18 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Mark R. Forwood

Experiments to design physical activity programs that optimize their osteogenic potential are difficult to accomplish in humans. The aim of this article is to review the contributions that animal studies have made to knowledge of the loading conditions that are osteogenic to the skeleton during growth, as well as to consider to what extent animal studies fail to provide valid models of physical activity and skeletal maturation. Controlled loading studies demonstrate that static loads are ineffective, and that bone formation is threshold driven and dependent on strain rate, amplitude, and duration of loading. Only a few loading cycles per session are required, and distributed bouts are more osteogenic than sessions of long duration. Finally, animal models fail to inform us of the most appropriate ways to account for the variations in biological maturation that occur in our studies of children and adolescents, requiring the use of techniques for studying human growth and development.


1997 ◽  
Vol 16 (4) ◽  
pp. 223-228 ◽  
Author(s):  
Itzchak Beiran ◽  
Benjamin Miller ◽  
Yedidia Bentur

1 Although calcium gluconate (CG) is recommended in the treatment of hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and controlled human or animal studies are limited. The study's objective is to compare the efficacy of 1% CG and normal saline irrigation for the treatment of HF eye injury in animals. 2 0.05 ml 2% HF was instilled to anesthetized rabbit's eyes. One minute later, four treatment groups were studies: (1) irrigation with normal saline followed by topical antibiotics, corticosteroids and cycloplegics for 48 h ( n=10); (2) irrigation with 1% CG followed by the same topical treatment ( n=9); (3) as group 1 and 1% CG drops over 48 h ( n=10); (4) as group 3, and injection of 1% CG subconjunctivally after irrigation ( n=9). 3 Corneal erosion area, corneal haziness, conjunctival status, vascularization (pannus) and acidity were assessed before injury, immediately after intitial treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein staining. 4 Conjunctival pH dropped from 6.0 - 6.5 to 2.5 - 3 after injury and increased to 6 - 6.5 after irrigation. Corneal erosion: smaller in groups 2, 3, significantly so at 2 days, but not different at 14 days. Corneal haziness: more severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2 - 4 eyes in each group. 5 It seems that for HF injury 1% CG did not have any significant advantage over saline irrigation and topical treatment only. It might have some initial and temporary effect on healing process especially that involving erosion. Given subconjunctivally, 1% CG may be toxic and worsens clinical outcome.


Background: Dry socket is one of the most common post-extraction complications with its incidence reaching up to 30% after impacted third molar extractions. In spite of its high incidence, there is no established treatment for the condition. Objectives: To investigate how efficient different management methods of Alveolar osteitis are, in regards to pain relief, healing process and reduction of the incidence. Materials and Methods: A literature search of “PubMed-MEDLINE” database was conducted using the keywords “dry socket management”, “alveolar osteitis”, “fibrinolytic alveolitis”, “post-extraction complications”. The inclusion criteria were clinical studies, case reports, reviews and human studies, related to alveolar osteitis published from 2011-2016, written in English language. The exclusion criteria were animal studies, studies that discussed other post-extraction complications, and in any other languages than English. Results: 63 articles were found and only 31 were reviewed. 18 out of 31 articles were included in the results, after reading the full text, due to lack of significant results in the rest of the articles. Out of these there were 12 clinical studies, 3 systematic reviews and 1 retrospective study. Conclusion: It was concluded that there is no specific management that could be rated as the best to treat dry socket, due to the lack of evidence to support the use of one management over the other, although there are many options that can help manage it and have proved to be highly effective recently and until today.


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