Search

Clinical orthopedics continuously aims to improve methods for bone formation. Clinical applications where bone formation is necessary include critical long bone defects in orthopedic trauma or tumor patients. Though some biomaterials combined with autologous stem cells significantly improve bone repair, critical-size damages are still challenged with the suitable implantation of biomaterials and donor cell survival. Extracellular matrix (ECM) is the fundamental structure in tissues that can nest and nourish resident cells as well as support specific functions of the tissue type. ECM also plays a role in cell signaling to promote bone growth, healing and turnover. In the last decade, the use of bone-derived ECMs or ECM-similar biomaterials have been widely investigated, including decellularized and demineralized bone ECM. In this article, we reviewed the current productions and applications of decellularized and demineralized bone matrices. We also introduce the current study of whole limb decellularization and recellularization.

Background: Autologous bone grafts, sourced from the iliac crest, are the gold standard for bone substitution in spine surgery. However, harvesting autografts increases the risk of postoperative complications. Bone allografts are another popular source of graft material, but their use is rapidly surpassing their availability. There has been considerable interest in manufactured bone graft substitutes, commonly referred to as osteobiologics, which mimic the properties of autologous bone and may be osteoconductive, osteoinductive, osteogenic, or a combination., Objective: Osteobiologics have been developed to mimic the properties of autologous bone, but their high cost and variable effectiveness raise questions about their value. This article explores the challenges and opportunities associated with the use of osteobiologics used to aid in bone healing in spinal fusion surgery within a value-based care framework. Spinal fusion treatments such as bone morphogenetic proteins, platelet-rich plasma, autologous conditioned serum, demineralized bone matrix, biomaterial scaffolds, stem cells, and cellular bone matrices are compared., Summary: Bone morphogenetic proteins are highly effective but often associated with serious risks; platelet-rich plasma shows promising results but lacks standardization in research protocols. Autologous conditioned serum is inconclusive and cost-effective, while demineralized bone matrix has variable effectiveness and limited data to use in anterior spinal fusions. Biomaterial scaffolds have limited application in the anterior spine but demonstrate high efficacy when it comes to spinal fusion. Stem cells demonstrate improved postsurgical outcomes but have low yield from bone marrow and potential risks associated with genetic engineering and cell therapy. Cellular bone matrices show promising results and have high fusion rates, yet there is currently no US Food and Drug Adminstration requirement for preclinical or clinical data before commercial usage. Although osteobiologics have considerable potential, their high price and uncertain efficiency raise questions concerning their usefulness in spinal fusion surgery. To ensure better patient outcomes, extensive research is needed to explore their utilization within a value-based care framework., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: Although several studies have reported successful fusion rates after oblique lumbar interbody fusion (OLIF) using allografts or dimerized bone matrix (DBM) instead of autografts, whether OLIF can achieve satisfactory solid fusion without the use of autografts remains unclear. This study investigated the real fusion rates after OLIF using allografts and DBM, which were evaluated using both dynamic radiographs and computed tomography scans., Methods: We enrolled 79 consecutive patients who underwent minimally invasive OLIF followed by percutaneous pedicle screw fixation. All patients were treated with OLIF between L2 and L5 and underwent radiographic and clinical follow-ups at 12, 18, and 24 months after surgery. Radiographic assessment of fusion was performed using the modified BrantigaSteffee-Fraser (mBSF) scale, which was categorized as follows: grades I (radiographic pseudoarthrosis), II (indeterminate fusion), and III (solid radiographic fusion). Other radiologic and clinical outcomes were evaluated using the following parameters: vertebral slippage distance, disc height, subsidence, Oswestry Disability Index (ODI), and visual analogue scale (VAS)., Results: Clinical outcomes demonstrated significant improvements in the VAS scores for back pain, leg pain, and ODI after surgery. Subsidence was present in 34 cases (35.4%) at 12 months postoperatively, which increased to 47.9% and reached 50.0% at 1.5 years and 2 years after surgery, respectively. The solid fusion rate after OLIF was 32.3% at 1 year, increased to 58.3% at 1.5 years, and reached 72.9% at 2 years. Radiographic pseudoarthrosis was 24.0% at 1 year, which decreased to 6.3% at 1.5 years and 3.1% at 2 years., Conclusion: OLIF is a safe and effective surgical procedure for the treatment of degenerative lumbar diseases. The mBSF scale, which simultaneously evaluates both dynamic angles and bone bridge formation, offers great reliability for the radiological assessment of fusion. Moreover, OLIF using allografts and DBM, which is performed on one or 2 levels at L2-5, can achieve satisfactory fusion rates within 2 years after surgery.

Digital bottom models are commonly used in many fields of human activity, such as navigation, harbor and offshore technologies, or environmental studies. In many cases, they are the basis for further analysis. They are prepared based on bathymetric measurements, which in many cases have the form of large datasets. Therefore, various interpolation methods are used for calculating these models. In this paper, we present the analysis in which we compared selected methods for bottom surface modeling with a particular focus on geostatistical methods. The aim was to compare five variants of Kriging and three deterministic methods. The research was performed with real data acquired with the use of an autonomous surface vehicle. The collected bathymetric data were reduced (from about 5 million points to about 500 points) and analyzed. A ranking approach was proposed to perform a complex and comprehensive analysis integrating typically used error statistics-mean absolute error, standard deviation and root mean square error. This approach allowed the inclusion of various views on methods of assessment while integrating various metrics and factors. The results show that geostatistical methods perform very well. The best results were achieved with the modifications of classical Kriging methods, which are disjunctive Kriging and empirical Bayesian Kriging. For these two methods, good statistics were calculated compared to other methods (for example, the mean absolute error for disjunctive Kriging was 0.23 m, while for universal Kriging and simple Kriging, it was 0.26 m and 0.25 m, respectively). However, it is worth mentioning that interpolation based on radial basis function in some cases is comparable to Kriging in its performance. The proposed ranking approach was proven to be useful and can be utilized in the future for choosing and comparing DBMs, mostly in mapping and analyzing seabed changes, for example in dredging operations. The research will be used during the implementation of the new multidimensional and multitemporal coastal zone monitoring system using autonomous, unmanned floating platforms. The prototype of this system is at the design stage and is expected to be implemented.

At present, the commonly used allogeneic bone powder in the clinic can be divided into nondemineralized bone matrix and demineralized bone matrix (DBM). Commonly used demineralizers include acids and ethylene diamine tetraacetic acid (EDTA). There may be some diversities between them. Also, the size of the bone particle can affects its cell compatibility and osteogenic ability. We produced different particle sizes i.e., < 75, 75-100, 100-315, 315-450, 450-650, and 650-1000 μm, and treated in three ways (nondemineralized, demineralized by EDTA, and demineralized by HCl). Scanning electron microscopy showed that the surface of the samples in each group was relatively smooth without obvious differences. The results of specific surface area and porosity analysis showed that they were significantly higher in demineralized bone powder than in nondemineralized bone powder, however, there was no significant difference between the two decalcification methods. The content of hydroxyproline in nondemineralized bone powder and EDTA-demineralized bone powder had no statistical difference, while HCl-demineralization had statistical significance compared with the former two, and the content increased with the decrease of particle size. The protein and BMP-2 extracted from HCl demineralized bone powder were significantly higher than that from nondemineralized bone powder and EDTA demineralized bone powder, and there were differences among different particle sizes. These results suggested the importance of demineralization mode and particle size of the allogenic bone powder and provided guidance for the choice of the most appropriate particle size and demineralization mode to be used in tissue bioengineering., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age.

Although the prevalence of undernutrition among women of reproductive age has declined in Bangladesh, the increase in the prevalence of overnutrition remains a major challenge. To achieve Sustainable Development Goal 2.2, it is important to identify the drivers of the double burden of malnutrition on women in Bangladesh. The Bangladesh Demographic and Health Survey, 2017-2018 was used to model the relationship between the double burden of malnutrition among women and the risk factors using a logistic regression model under the classical and Bayesian frameworks and performed the comparison between the regression models based on the narrowest confidence interval. Regarding the Bayesian application, the Metropolis-Hastings algorithm with two types of prior information (historical and noninformative prior) was used to simulate parameter estimates from the posterior distributions. The Boruta algorithm was used to determine the significant predictors. Almost half of reproductive aged women experienced a form of malnutrition (12% were underweight, 26.1% were overweight, and 6.8% were obese). In terms of the narrowest interval estimate, it was found that Bayesian logistic regression with informative priors performs better than the noninformative priors and the classical logistic regression model. Women who were older, highly educated, from rich families, unemployed, and from urban residences were more likely to experience the double burden of malnutrition. This study recommended using the historical prior as the informative prior rather than the flat/noninformative prior to estimating the parameter uncertainty if historical data are available. The double burden of malnutrition among women is a major public health challenge in Bangladesh. This study was to determine the impact of effective risk factors on the double burden of malnutrition among women by applying the Bayesian framework. Using both informative and noninformative priors, "historical prior" was proposed as informative prior information. The main strength is that the proposed prior (historical prior) provided improved estimation as compared to the flat prior distribution., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Orthobiologics have gained much popularity in recent years but there has not been a large amount of clinical evidence to support their use. In the limited research that has been published, they have been shown to be effective and safe. They can assist in earlier return to activity with the avoidance of surgery. They can also augment current surgical practice to aid in healing and return to sport with few complications. With new medical innovation, there is unfortunately a higher cost for these products. The use of orthobiologics will only grow and so will the need for high-level clinical evidence., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

An important question is whether consensus mechanisms for copper monooxygenase enzymes such as peptidylglycine monooxygenase (PHM) and dopamine β-monooxygenase (DBM) generated via computational and spectroscopic approaches account for important experimental observations. We examine this question in the light of recent crystallographic and QMMM reports which suggest that alternative mechanisms involving an open to closed conformational cycle may be more representative of a number of experimental findings that remain unaccounted for in the canonical mononuclear mechanisms. These include (i) the almost negligible reactivity of the catalytic copper site (CuM) with oxygen in the absence of substrate, (ii) the carbonyl chemistry and in particular the substrate-induced activation exemplified by the lowered CO stretching frequency, (iii) the peroxide shunt chemistry which demands an intermediate that facilitates equilibrium between a Cu(II)-peroxo state and a Cu(I)-dioxygen state, and (iv) clear evidence for both closed and open conformational states in both PHM and DBM. An alternative mechanism involving a dinuclear copper intermediate formed via an open to closed conformational transition appears better able to accommodate these experimental observations, as well as being shown by QMMM methodologies to be energetically feasible. This suggests that future experiments should be designed to distinguish between these competing mechanisms and the factors that govern the oxygen reactivity of the copper centers. In particular, determining how oxygen reactivity is activated by binding of substrate, should be considered an important new challenge., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bone graft extenders are being used more in spine surgery as a substitute for iliac crest bone graft. However, potential conflict of interest could impact average fusion rates. The purpose of this study was to evaluate whether fusion rates reported in the literature were different in papers evaluating bone graft substitutes and extenders when there was potential conflict of interest versus no potential conflict of interest., Methods: Pubmed was searched for studies evaluating fusion rates when bone graft extenders including demineralized bone matrix, hydroxyapatite, and tricalcium sulfate were used. Studies were screened for one or two level fusions and for degenerative spinal conditions. The average fusion rates of subgroups were compared using unpaired Student's t-tests., Results: 1928 studies were evaluated. 86 studies were included in the study. The fusion rates varied from 4 to 100%. There were 24 studies with a potential conflict of interest and 62 studies with no conflict of interest. The average fusion rate of all the studies was 84.63% with standard deviation of 18.33%. The average fusion rates of those studies with conflict of interest was 80.93% versus 86.06% without conflict of interest. This was not statistically significant (p>0.07). The average fusion rate of studies evaluated by CT scan was 79.8% versus 87.9% without CT. The average fusion rate of studies that employed an independent reviewer to evaluate the fusion was 82.61% versus 85.63% for studies with no independent reviewer., Conclusion: There is a great variability in the reported fusion rates of bone graft extenders. Counter to expectations, average fusion rates were lower in the studies where there was a potential conflict of interest. The use of CT scans and an independent reviewer seem to account for the lower reported fusion rates, and may be a means of negating the potential conflicts of interest in fusion studies., Level of Evidence: 2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd on behalf of North American Spine Society.)

Objective: This article aims to review the epidemiology, etio-pathogenesis and updates in clinical diagnostics and management of unicameral bone cysts (UBC)., Methods: A computerized literature search using Cochrane database of systematic reviews, EMBASE and PubMed was performed. MeSH (Medical Subject Headings) terms used in searches included the following sub-headings: "unicameral bone cyst", "epidemiology", "etiology", "pathogenesis", "diagnosis", "management" and "surgery". Studies were analyzed based on clinical relevance for the practicing orthopedic surgeon., Results: UBC accounts for 3% of all bone tumors and is asymptomatic in most cases. Nearly 85% of cases occur in children and adolescents, with more than 90% involving the proximal humerus and proximal femur. Despite multiple theories proposed, the exact etiology is still unclear. Diagnosis is straightforward, with radiographs and MRI aiding in it. While non-surgical treatment is recommended in most cases, in those warranting surgery, combined minimal-invasive techniques involving decompression of cyst and stabilization have gained importance in recent times., Conclusion: There is variation in the diagnosis and treatment of UBCs among surgeons. Due to the vast heterogeneity of reported studies, no one method is the ideal standard of care. As most UBCs tend to resolve by skeletal maturity, clinicians need to balance the likelihood of successful treatment with morbidity associated with procedures and the risks of developing a pathological fracture., Study Design: Review Article., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2022.)

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO 4 , CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO 4 ·0.5H 2 O, CSH) were produced by heating gypsum (CaSO 4 ·2H 2 O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.

The effect of luminescent enhancement under exchange of the auxiliary ligand in Europium(III) tris(1,3-diphenyl-1,3-propanedionato) monohydrate was investigated by steady-state and time-resolved transient absorption spectroscopy. The excited state relaxation dynamics of this complex was analysed through a comparison of the experimental data obtained for several model compounds, namely Eu(DBM) 3 ·NH 3 , Eu(DBM) 3 .EDA, Eu(DBM) 3 .Phen, Al(DBM) 3 and dibenzoylmethane (DBM) in various solutions and polymer matrices. The results show there is no linear relationship between enhancement of the emission quantum yield and the luminescent lifetime, which suggests that the auxiliary ligand reduces the rate of nonradiative relaxation of the lanthanide ion, but also affects the excited state energy transfer from ligand to metal ion. Transient absorption data shows a clear correlation between the efficiency of the energy transfer and the degree of triplet state population expressed by an amplification of the signal for its excited state absorption band on going from Eu(DBM) 3 ·H 2 O to the Eu(DBM) = .L complex. The results show that this auxiliary ligand exchange acts as a "switch" turning the intersystem crossing on or off as a competitive pathway for excited state relaxation of the europium(III) complexes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In fracture surgery, large bone defects and non-unions often require bone transplantation, and alternatives to autograft bone substitutes in the form of allografts from bone banks and the derivate demineralised bone matrix (DBM) are widely used. With a focus on efficacy, clinical evidence, safety, cost, and patient acceptance, this review evaluated the difference between allogeneic allograft or DBM as a bone substitute in trauma surgery. The efficacy in supporting bone healing from allograft and DBM is highly influenced by donor characteristics and graft processing. Mechanical stability is achieved from a structural graft. Based on the existing literature it is difficult to identify where DBM is useful in trauma surgery, and the level of evidence for the relevant use of allograft bone in trauma is low. The risk of transmitting diseases is negligible, and the lowest risk is from DBM due to the extensive processing procedures. A cost comparison showed that DBM is significantly more expensive. The experiences of dental patients have shown that many patients do not want to receive allografts as a bone substitute. It is not possible to definitively conclude whether it makes a difference if allograft or DBM is used in trauma surgery. It is ultimately the surgeon's individual choice, but this article may be useful in providing considerations before a decision is made., Competing Interests: Declaration of Interest Statement The author declare that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Demineralized bone matrix (DBM), a potential alternative to autologous bone-graft, has been increasingly used for clinical bone repair; however, its application in larger defects isn't successful partly due to the rapid dispersion of DBM particles and relatively lower osteoinductivity. Here, a novel strategy is created to complement the osteoinductivity of DBM by incorporating DBM in biopolymer hydrogel combined with the abrogation of BMP antagonism. Combined treatment of DBM + noggin-suppression displays increased osteogenic potency of human bone marrow mesenchymal stem cells (hBMSCs) in vitro . Injectable chitosan (MeGC)-based hydrogel with heparinization (Hep-MeGC) is further developed to localize and stabilize DBM. Noggin-suppression reveals the significant increase in osteogenesis of hBMSCs in the photopolymerizable Hep-MeGC hydrogels with the encapsulation of DBM. Moreover, the combination of DBM + noggin-suppression in the injectable Hep-MeGC hydrogel displays a robust bone healing in mouse critical-sized calvarial defects in vivo . The mechanistic analysis demonstrates that noggin-suppression increased DBM osteoinductivity by stimulating endogenous BMP/Smad signals. These results have shown promise in DBM's ability as a prominent bone grafting material while being coupled with gene editing mechanism and a localizing three-dimensional scaffold. Together, this approach poses a significant increase in the efficiency of DBM-mediated craniofacial bone repair and dental osteointegration., Competing Interests: Conflict of Interest The authors indicated no potential conflicts of interest.

Eu 3+ -β-diketonate complexes are used, for example, in solid-state lighting (SSL) or light-converting molecular devices. However, their low emission quantum efficiency due to water molecules coordinated to Eu 3+ and low photostability are still problems to be addressed. To overcome such challenges, we synthesized Eu 3+ tetrakis complexes based on [Q][Eu(tfaa) 4 ] and [Q][Eu(dbm) 4 ] (Q1 = C 26 H 56 N + , Q2 = C 19 H 42 N + , and Q3 = C 17 H 38 N + ), replacing the water molecules in the tris stoichiometry. The tetrakis β-diketonates showed desirable thermal stability for SSL and, under excitation at 390 nm, they displayed the characteristic Eu 3+ emission in the red spectral region. The quantum efficiencies of the dbm complexes achieved values as high as 51%, while the tfaa complexes exhibited lower quantum efficiencies (28-33%), but which were superior to those reported for the tris complexes. The structures were evaluated using the Sparkle/PM7 model and comparing the theoretical and the experimental Judd-Ofelt parameters. [Q1][Eu(dbm) 4 ] was used to coat a near-UV light-emitting diode (LED), producing a red-emitting LED prototype that featured the characteristic emission spectrum of [Q1][Eu(dbm) 4 ]. The emission intensity of this prototype decreased only 7% after 30 h, confirming its high photostability, which is a notable result considering Eu 3+ complexes, making it a potential candidate for SSL., (© 2019 John Wiley & Sons, Ltd.)

Cerebral small vessel disease(s) (SVD) results from pathological changes of the small blood vessels in the brain and is common in older people. The diagnostic features by which SVD manifests in brain includes white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and atrophy. In the present study, we use in vivo magnetic resonance imaging (MRI) to characterize brain morphometry and longitudinal relaxation time (T1) of spontaneously hypertensive rats (SHRs) to study the contribution of chronic hypertension to SVD relevant pathology. Male SHR and Wistar-Kyoto (WKY) rats underwent 3D variable flip angle spoiled gradient echo brain MRI at 9.4 T at early (seven weeks old) and established (19 weeks old) stages of hypertension. The derived proton density weighted and T1 images were utilized for morphometry and to characterize T1 properties in gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Custom tissue probability maps were constructed for accurate computerized whole brain tissue segmentations and voxel-wise analyses. Characteristic morphological differences between the two strains included enlarged ventricles, smaller corpus callosum (CC) volumes and general 'thinning' of CC in SHR compared to WKY rats at both age groups. While we did not observe parenchymal T1 differences, the T1 of CSF was elevated in SHR compared to controls. Collectively these findings indicate that SHRs develop WM atrophy which is a clinically robust MRI biomarker associated with WM degeneration., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Background: Propolis is known for its antioxidant, immune response modulating, and wound healing effects. In the present study in order to determine the bone healing capacity of the propolis extract, a critical sized, nonunion, radial bone defect model was repaired in rat, using chitosan and demineralized bone matrix (DBM) scaffolds along with propolis extract., Materials and Methods: Seventy-two radial bone defects in 36 healthy male rats were randomly divided into 6 groups (n = 12/group). The groups included autograft, defect or untreated group, chitosan, DBM, chitosan and propolis (chitosan-propolis), and DBM and propolis (DBM-propolis). The bone repairing capability was characterized using radiography at 28th, 42nd and 56th postoperative days. Gross morphologic, histopathologic, histomorphometric and biomechanical examinations were performed following euthanasia at the 56th post-operative day., Results: The DBM-propolis group, showed better structural and biomechanical properties compared to the untreated, DBM, chitosan and chitosan-propolis groups. The defect site in the chitosan and untreated groups were mainly restored by fibrous connective tissue while the lesions in the autograft group were mostly filled by cartilage and a lesser amount of woven bone. The woven bone, and the hyaline cartilage were the main constituents of the newly formed tissues in the DBM-propolis group, at the 56th day after injury., Conclusion: The results of this study showed that percutaneous injection of diluted aqueous propolis extract in the bone defect (25 mg/defect) can improve bone formation in the critical radial bone defect in rat. Since there was no significant difference between the autograft and DBM-propolis group, probably this therapeutic strategy has high potential in augmentation of autologous bone grafting., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Transcription factors (TFs), which play a vital role in regulating gene expression, are prevalent in all organisms and characterization of them may provide important clues for understanding regulation in vivo. The present study reports a genome-wide investigation of TFs in the diamondback moth, Plutella xylostella (L.), a worldwide pest of crucifers. A total of 940 TFs distributed among 133 families were identified. Phylogenetic analysis of insect species showed that some of these families were found to have expanded during the evolution of P. xylostella or Lepidoptera. RNA-seq analysis showed that some of the TF families, such as zinc fingers, homeobox, bZIP, bHLH, and MADF&#95;DNA&#95;bdg genes, were highly expressed in certain tissues including midgut, salivary glands, fat body, and hemocytes, with an obvious sex-biased expression pattern. In addition, a number of TFs showed significant differences in expression between insecticide susceptible and resistant strains, suggesting that these TFs play a role in regulating genes related to insecticide resistance. Finally, we identified an expansion of the HOX cluster in Lepidoptera, which might be related to Lepidoptera-specific evolution. Knockout of this cluster using CRISPR/Cas9 showed that the egg cannot hatch, indicating that this cluster may be related to egg development and maturation. This is the first comprehensive study on identifying and characterizing TFs in P. xylostella. Our results suggest that some TF families are expanded in the P. xylostella genome, and these TFs may have important biological roles in growth, development, sexual dimorphism, and resistance to insecticides. The present work provides a solid foundation for understanding regulation via TFs in P. xylostella and insights into the evolution of the P. xylostella genome.

Long non-coding RNAs (lncRNAs) are of particular interest because of their contributions to many biological processes. Here, we present the genome-wide identification and characterization of putative lncRNAs in a global insect pest, Plutella xylostella. A total of 8096 lncRNAs were identified and classified into three groups. The average length of exons in lncRNAs was longer than that in coding genes and the GC content was lower than that in mRNAs. Most lncRNAs were flanked by canonical splice sites, similar to mRNAs. Expression profiling identified 114 differentially expressed lncRNAs during the DBM development and found that majority were temporally specific. While the biological functions of lncRNAs remain uncharacterized, many are microRNA precursors or competing endogenous RNAs involved in micro-RNA regulatory pathways. This work provides a valuable resource for further studies on molecular bases for development of DBM and lay the foundation for discovery of lncRNA functions in P. xylostella., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Tb doped polyvinyl alcohol: polyvinyl pyrrolidone blends with dibenzoylmethane (DBM) and 1, 10 Phenanthroline (Phen) have been prepared by solution cast technique. Bond formation amongst the ligands and Tb 3+ ions in the doped polymer has been confirmed employing Fourier Transform Infrared (FTIR) techniques. Optical properties of the Tb 3+ ions have been investigated using UV-Vis absorption, excitation and fluorescence studies excited by different radiations. Addition of dimethylbenzoate and 1, 10 Phenanthroline to the polymer blend increases the luminescence from Tb 3+ ions along with energy transfer from the polymer blend itself. Luminescence decay curve analysis affirms the non-radiative energy transfer from DBM and Phen to Tb 3+ ions, which is identified as the reason behind this enhancement. The fluorescence decay time of PVA-PVP host decreases from 6.02ns to 2.31ns showing an evidence of energy transfer from the host blend to the complexed Tb ions. Similarly the lifetime of DBM and Phen and both in the blend reduces in the complexed system showing the feasibility of energy transfer from these excited DBM and Phen to Tb 3+ and is proposed as the cause of the above observations. These entire phenomena have been explained by the energy level diagram., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To allow bone defect regeneration, autologous bone grafting still represents the gold standard. However, autograft harvesting has limitations, including an additional surgery, donor site morbidity, and limited availability. Demineralized bone matrix (DBM) would represent an alternative, yet lacks sufficient osteoinductive properties. Combining DBM with a potent agent, such as bone morphogenetic protein-2 (BMP-2) might be a feasible alternative approach, optimizing an established grafting material with strong osteoinductive properties. A unique mixing device has been developed that enables perioperative handling to reach a homogeneous and standardized paste for bone defect filling. DBM proved in vitro to be a suitable carrier for BMP-2, with a documented release over 56 days at concentrations sufficient to stimulate osteogenic differentiation. At the end of the elution experiment, 56 days, bioactive BMP was still captured within the DBM. Using a sheep drill hole defect model, DBM perioperatively mixed with BMP-2 showed strong osteoinductive properties comparable to those of autologous bone and outnumbering the one of DBM alone or empty defects. Bone defect healing was enabled at diaphyseal and metaphyseal defects and thus BMP-2-doped DBM represented an easy perioperative enriching method and an efficient carrier for BMP-2. With the comparability to the clinical gold standard autologous bone, DBM mixed with BMP-2 might serve as possible alternative grafting material enabling a controlled osteogenic stimulation.

Background: Spinal fusions are commonly performed in the US each year for various spinal pathologies. There are multiple commercially available graft material options for these procedures, including an abundance of demineralized bone matrix (DBM) products., Methods: This study reviews, clearly organizes, and puts forth meaningful information on select biological and physical properties of several commercially available DBM products. In addition, we provide an alternative classification method of DBM products by carrier., Results: This review takes a closer look at the commercial and distributor practices of these products and companies in order to increase transparency between the consumer and source companies., Conclusions: We propose a novel patient-centered approach to DBM product selection. This requires prioritizing patient safety, product effectiveness, and product transparency. This review offers a practical paradigm to facilitate informed product choice for surgeons and hospital systems alike., Competing Interests: There are no conflicts of interest.

Objective: This study aimed to compare the clinical and radiologic outcomes of patients with subaxial cervical injury who underwent anterior cervical discectomy and fusion (ACDF) with autologous iliac bone graft or polyetheretherketone (PEEK) cages using demineralized bone matrix (DBM)., Methods: From January 2005 to December 2010, 70 patients who underwent one-level ACDF with plate fixation for post-traumatic subaxial cervical spinal injury in a single institution were retrospectively investigated. Autologous iliac crest grafts were used in 33 patients (Group I), whereas 37 patients underwent ACDF using a PEEK cage filled with DBM (Group II). Plain radiographs were used to assess bone fusion, interbody height (IBH), segmental angle (SA), overall cervical sagittal alignment (CSA, C2-7 angle), and development of adjacent segmental degeneration (ASD). Clinical outcome was assessed using a visual analog scale (VAS) for pain and Frankel grade., Results: The mean follow-up duration for patients in Group I and Group II was 28.9 and 25.4 months, respectively. All patients from both groups achieved solid fusion during the follow-up period. The IBH and SA of the fused segment and CSA in Group II were better maintained during the follow-up period. Nine patients in Group I and two patients in Group II developed radiologic ASD. There were no statistically significant differences in the VAS score and Frankel grade between the groups., Conclusion: This study showed that PEEK cage filled with DBM, and plate fixation is at least as safe and effective as ACDF using autograft, with good maintenance of cervical alignment. With advantages such as no donor site morbidity and no graft-related complications, PEEK cage filled with DBM, and plate fixation provide a promising surgical option for treating traumatic subaxial cervical spine injuries.

The key drawback of using demineralized bone matrix (DBM) is its low initial mechanical stability due to the severe depletion of mineral content. In the present study, we investigated the long-term regeneration of DBM in a critical size bone defect model and investigated the remineralization after 6 months. Bone defects were created in the cranium of male Wistar rats which were filled with DBM or left empty as negative control. In vivo bone formation was monitored with computed tomography after 11, 19, and 26 weeks postoperatively. After 6 months, parietal bones were subjected to micro-CT. Mineral content was determined with spectrophotometric analysis. After 11 weeks the DBM-filled bone defects were completely closed, while empty defects were still open. Density of the DBM-treated group increased significantly while the controls remained unchanged. Quantitative analysis by micro-CT confirmed the in vivo results, bone volume/tissue volume was significantly lower in the controls than in the DBM group. The demineralization procedure depleted the key minerals of the bone to a very low level. Six months after implantation Ca, P, Na, Mg, Zn, and Cr contents were completely restored to the normal level, while K, Sr, and Mn were only partially restored. The remineralization process of DBM is largely complete by the 6th month after implantation in terms of bone density, structure, and key mineral levels. Although DBM does not provide sufficient sources for any of these minerals, it induces a faster and more complete regeneration process. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1336-1342, 2016., (© 2015 Wiley Periodicals, Inc.)

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo . The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells., (© 2015 Wiley Periodicals, Inc.)

Environmental enrichment is a model of increased structural brain plasticity. Previous histological observations have shown molecular and cellular changes in a few pre-determined areas of the rodent brain. However, little is known about the time course of enrichment-induced brain changes and how they distribute across the whole brain. Here we expose adult mice to three weeks of environmental enrichment using a novel re-configurable maze design. In-vivo MRI shows volumetric brain changes in brain areas related to spatial memory, navigation, and sensorimotor experience, such as the hippocampal formation and the sensorimotor cortex. Evidence from a second cohort of mice indicates that these plastic changes might occur as early as 24h after exposure. This suggests that novel experiences are powerful modulators of plasticity even in the adult brain. Understanding and harnessing the underlying molecular mechanisms could advance future treatments of neurological disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Spinal fusions are being performed for various pathologies of the spine such as degenerative diseases, deformities, tumors and fractures. Recently, other bone substitutes such as demineralized bone matrix (DBM) have been developed for spinal fusion. Therefore, this study was conducted to evaluate the intertransverse posterolateral fusion with the Bovine fetal growth plate (DCFGP) and compare it with commercial DBM in rat model., Methods: A total of 16 mature male rats (aged 4 months and weighing 200-300 g) were randomly divided in two groups. After a skin incision on posterolateral site, two separate fascial incisions were made 3 mm from the midline. A muscle-splitting approach was used to expose the transverse processes of L4 and L5. Group I (n = 8) underwent with implanted Bovine fetal growth plate among decorticated transverse processes. In group II (n = 8) commercial DBM was placed in the same manner. Fusion was evaluated by manual palpation, radiographical, gross and histopathological analysis., Results: The manual palpation, radiological, gross and histopathological findings indicate high potential of the DCFGP in spinal fusion. At the 42nd postoperative day, new bone formation as evidenced by a bridge between L4 and L5 was visualized in all rats implanted with DCFGP and commercial DBM. The newly formed bone tissue was observed in all implanted areas on the 42nd day after operation in the two groups., Conclusions: The spinal fusion of the animals of both groups demonstrated more advanced osteogenic potential and resulted in proper fusion of the transverse process of lumbar vertebra.

Both decalcified bone matrix (DBM) and fibrin gel possess good biocompatibility, so they are used as scaffolds to culture bone marrow mesenchymal stem cells (BMSCs). The feasibility and efficacy of using compound material being made of decalcified bone matrix and fibrin gel as a three-dimensional scaffold for bone growth were investigated. BMSCs were isolated from the femur of rabbit, then seeded in prepared scaffolds after incubation for 28 days in vitro. In vivo: 30 New Zealand White Rabbits received bone defect in left radius and divided three treatment groups randomly: (1) BMSCs/decalcified bone matrix/fibrin glue as experimental group; (2) decalcified bone matrix/fibrin glue without cells as control group; (3) nothing was implanted into the bone defects as blank group. The observation period of specimens was 12 weeks, and were analyzed bone formation in terms of serum proteomics (2D-PAGE and MALDI-TOF-TOF-MS), hematoxylin-eosin (HE) staining, ALP staining, and Osteopontin immunofluorescence detection. The experimental group present in three peculiar kinds of proteins, whose Geninfo identifier (GI) number were 136466, 126722803, and 126723746, respectively, correspond to TTR protein, ALB protein, RBP4 protein, and the histological inspections were superior to the other group. The content of osteopontin in experimental group was significantly higher than control group (p <  0.05). The overall results indicated that a combined material being made of BMSCs/decalcified bone matrix/fibrin glue can result in successful bone formation and decalcified bone matrix/fibrin glue admixtures can be used as a scaffold for bone tissue engineering., (Copyright © 2013 Wiley Periodicals, Inc.)

The aim of this study was to histologically evaluate the performance of demineralized bone matrix (DBM) when compared with a blood clot in addition to an occlusive barrier in the bone regeneration process for bone defects in a rabbit model. Prefabricated metallic capsules with 4.5 mm and 3.5 mm dimensions were placed in five adult rabbit skulls. At the right side, the capsule was filled with DBM, and the clot was located on the left side. The barriers were supplied with a 0.5 mm horizontal peripheral flap and a vertical edge, fitting tightly into a circular slit prepared by a trephine in the skull. After a healing period of three months, the animals were sacrificed, and the samples were prepared for histological and histomorphometric analyses after capsule removal. Trabecular and medullar bone percentages were calculated from the different areas of the newly formed bone inside the metallic barriers, and non-parametric statistical analysis was used to describe the findings. The results showed a complete filling of newly formed bone inside the capsules of both groups. Less mature bone tissue was observed in the upper third of all samples, and a higher trabecular area was observed in the samples with DBM. The use of barriers resulted in the augmentation of newly formed bone in a three-month period. However, a higher trabecular area was observed in the barriers filled with DBM., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches., (© 2013.)

Orthopedic injuries are common and a source of much misery and economic stress. Several relevant tissues, such as cartilage, meniscus, and intra-articular ligaments, do not heal. And even bone, which normally regenerates spontaneously, can fail to mend. The regeneration of orthopedic tissues requires 4 key components: cells, morphogenetic signals, scaffolds, and an appropriate mechanical environment. Although differentiated cells from the tissue in question can be used, most cellular research focuses on the use of mesenchymal stem cells. These can be retrieved from many different tissues, and one unresolved question is the degree to which the origin of the cells matters. Embryonic and induced pluripotent stem cells are also under investigation. Morphogenetic signals are most frequently supplied by individual recombinant growth factors or native mixtures provided by, for example, platelet-rich plasma; mesenchymal stem cells are also a rich source of trophic factors. Obstacles to the sustained delivery of individual growth factors can be addressed by gene transfer or smart scaffolds, but we still lack detailed, necessary information on which delivery profiles are needed. Scaffolds may be based on natural products, synthetic materials, or devitalized extracellular matrix. Strategies to combine these components to regenerate tissue can follow traditional tissue engineering practices, but these are costly, cumbersome, and not well suited to treating large numbers of individuals. More expeditious approaches make full use of intrinsic biological processes in vivo to avoid the need for ex vivo expansion of autologous cells and multiple procedures. Clinical translation remains a bottleneck., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective(s): Ex vivo expansion of hematopoitic stem cells is an alternative way to increase umbilical cord blood (UCB)-CD34+ cells for bone marrow transplantation. For this purpose demineralized bone matrix (DBM) and mineralized bone allograft (MBA) as two scaffolds based on bone matrix and stem cell niche, were simultaneously used to enhance the effect of human mesenchymal progenitor cells (MPCs) - unrestricted somatic stem cells (USSCs) - as a feeder layer., Materials and Methods: USSCs were isolated and characterized by morphological and immunological analysis then seeded on both scaffolds as a feeder layer. UCB-CD34(+) were isolated by MACS method and were co-culture expanded by USSC in 3D and 2D environments. After 3 weeks expansion, cells were counted and were assessed by karyotype, flow cytometry, clonogenic activity, and long-term culture-initiating cells (LTC-IC)., Results: Co-culture expansion in DBM and MBA was 29.22-fold and 27.77-fold, no significant differences in colony and LTC-IC were obtained. Maximum number of colonies belonged to the day 14 with the 73% CFU-GM (Colony Forming Unit- Granulocyte/Macrophage) in contrast to the day 0 which was BFU-E/CFU-E (Burst/Colony Forming Unit-Erythroid). Flow cytometry indicated that the percentage of CD34+ marker was decreased in USSC co-culture and the highest percentage was observed in simple 2D culture., Conclusion: Because of acid extraction in the DBM production process, mineral materials were removed and the protein background that was more flexible was presented. Therefore these results suggest that USSC-DBM can be a suitable ex vivo mimicry niche by intensifying of surface/volume ratio and supporting the stem cell differentiation and expansion.

In order to achieve successful clinical outcomes, biomaterials used for bone grafts must possess a number of traits including biocompatibility and osteoconductivity. These materials must also demonstrate appropriate mechanical stability to withstand handling as well as support potentially significant stresses at the implant site. Synthetic and natural polymer scaffolds used for bone tissue engineering (BTE) often lack necessary mechanical properties. Our goal was to internally mineralize natural collagenous matrix, thereby increasing mechanical properties of the material to useful levels. Published methods for intrafibrillar collagen mineralization were applied to clinically relevant-sized constructs but did not successfully deposit mineral in the interior of the constructs. To address this limitation, we developed a new technique for the remineralization of demineralized bone matrix (DBM) based on alternating solution immersion, or ASI. Mineral was removed from equine bone specimens, leaving behind a demineralized bone matrix (DBM). This matrix provides a framework for the nucleation and growth of a replacement mineral phase. Plain film radiography and microcomputed tomography (microCT) indicated accumulation of mineral within the DBM, and mechanical testing (3 point bending and compression) revealed a significant increase in stiffness between the DBM and the remineralized bone matrix (RBM). We believe this remineralization process will be useful in the preparation of stiff and strong allografts for clinical application., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

To what extent does musical practice change the structure of the brain? In order to understand how long-lasting musical training changes brain structure, 20 male right-handed, middle-aged professional musicians and 19 matched controls were investigated. Among the musicians, 13 were pianists or organists with intensive practice regimes. The others were either music teachers at schools or string instrumentalists, who had studied the piano at least as a subsidiary subject, and practiced less intensively. The study was based on T1-weighted MR images, which were analyzed using deformation-based morphometry. Cytoarchitectonic probabilistic maps of cortical areas and subcortical nuclei as well as myeloarchitectonic maps of fiber tracts were used as regions of interest to compare volume differences in the brains of musicians and controls. In addition, maps of voxel-wise volume differences were computed and analyzed. Musicians showed a significantly better symmetric motor performance as well as a greater capability of controlling hand independence than controls. Structural MRI-data revealed significant volumetric differences between the brains of keyboard players, who practiced intensively and controls in right sensorimotor areas and the corticospinal tract as well as in the entorhinal cortex and the left superior parietal lobule. Moreover, they showed also larger volumes in a comparable set of regions than the less intensively practicing musicians. The structural changes in the sensory and motor systems correspond well to the behavioral results, and can be interpreted in terms of plasticity as a result of intensive motor training. Areas of the superior parietal lobule and the entorhinal cortex might be enlarged in musicians due to their special skills in sight-playing and memorizing of scores. In conclusion, intensive and specific musical training seems to have an impact on brain structure, not only during the sensitive period of childhood but throughout life.

Background: In this study, the effectiveness of Iranian Tissue Bank-produced demineralized bone matrix (ITB-DBM), beta-tricalcium phosphate (βTCP), and Bio-Oss(®) (Geistlich Pharma AG, Wolhusen, Switzerland) were evaluated and compared with double controls. The main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control) defects., Methods: In this study, 40 male Wistar rats were selected and divided into four groups, In each group, there were ten rats with two defects in their calvarias; one of them is considered as control and the other one was treated with ITB-DBM (group 1), BIO-OSS (group2), and βTCP (group 3), respectively. But in group 4, both defects were considered as control. The amount of inflammation and new bone formation were evaluated at 4 and 10 weeks. In the first group, one defect was filled with ITB-DBM; in the second group, one defect was filled with Bio-Oss; in the third group, one defect was filled with βTCP; and in the fourth group, both defects were left unfilled. Zeiss microscope (Carl Zeiss AG, Oberkochen, Germany) and Image Tool(®) (version 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX) software were used for evaluation. SPSS Statistics (IBM Corp, Somers, NY) was used for statistical analysis., Results: Maximum bone formation at 4 and 10 weeks were observed in the ITB-DBM group (46.960% ± 4.366%, 94.970% ± 0.323%), which had significant difference compared with the other groups (P < 0.001). Ranking second was the Bio-Oss group and third, the βTCP group. Bone formation in the group with two unfilled defects was much more significant than in the other controls beside the Bio-Oss and βTCP after 10 weeks (29.1 ± 2.065, 29.05 ± 1.649), while this group had the least bone formation compared with the other controls at week 4 (2.100% ± 0.758%, 1.630% ± 0.668%, P < 0.001)., Conclusion: Overall, the ITB-DBM group showed the best results, although the results for other experimental groups were unfavorable. The authors conclude that human DBM (ITB-DBM) should be offered as an alternative for bone regeneration in animals, such as horses, as well as in humans, especially for jaw reconstruction. In relation to bone regeneration in control defects, the effect of experimental material on controls was apparent during the initial weeks.