Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration – an in silico analysis

AbstractLarge bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term.

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The Incorporation of Platelet-rich Plasma into Calcium Phosphate Cement Enhances Bone Regeneration in Osteoporosis

January 2018 - Pain Physician ◽

10.36076/ppj.2014/17/e737 ◽

2014 ◽

Vol 6;17 (6;12) ◽

pp. E737-E745

Author(s):

Kyung-Hoon Kim

Keyword(s):

Bone Regeneration ◽

Trabecular Bone ◽

Volume Fraction ◽

Platelet Rich Plasma ◽

Bone Volume ◽

Filler Materials ◽

Trabecular Bone Volume ◽

Mineral Density ◽

Bone Volume Fraction ◽

Trabecular Thickness

Background: Polymethyl methacrylate (PMMA) bone cement is widely used for osteoplasty. However, previous studies have demonstrated the adverse effects of PMMA due to its excessive stiffness and heat production. Recently, calcium phosphate cement (CPC) that overcomes those negative effects has been successfully applied in osteoplasty. The potential problem of CPC is markedly less initial stiffness. It leads to progressive, repeated collapse in the treated vertebra before CPC has been replaced by new bone that would provide substantial improvement in compressive strength and stiffness. The activated platelets in platelet-rich plasma (PRP) release a high concentration of growth factors which play an important role in bone healing. Objective: To investigate whether PRP could accelerate the osteoconduction of CPC and enhance the bone strength of the treated vertebra in an animal model. Study Design: Controlled animal study. Setting: Laboratory animal study, Methods: Thirty-two female Sprague-Dawley rats were ovariectomized at 8 weeks of age. After 3 months, they were randomly divided into 4 groups and received cement augmentation in the fifth caudal spine with different filler materials; sham-operated rats (S), PMMA (P), CPC (C), and CPC + PRP (CP). Bone mineral density (BMD) and trabecular type-associated morphological parameters, including trabecular bone volume fraction and trabecular thickness in the augmented caudal spine, were evaluated by micro-computed tomography (mirco-CT) 2 weeks after the cementoplasty. Histological analysis was also performed to compare the bone regeneration. Results: The trabecular bone volume fraction in the CP group was significantly greater than those of all the other groups. Trabecular thickness was higher in the CP group than the S and P groups. This augmented trabecular structure in the CP group accordingly showed higher BMD. Histological evaluations showed significantly more bone regeneration in the CP group. Limitations: There has been a concern that the effect of PRP would be dependent on the species, and might show different results in humans. Baseline values of micro-CT analysis were not measured, which could have provided exact evidence of the changes in trabecular microarchitecture parameters and cement resorption profiles. Finally, caudal vertebrae with filler materials used in biological study should have been compared by their mechanical properties using biomechanical evaluations for a more coherent study, which was not possible due to technical problems. Conclusions: Incorporating PRP into CPC could accelerate osteoconduction in the augmented vertebra leading to improvement of trabecular bone microarchitecture and BMD in rats. Key words: Bone mineral density, calcium phosphates, cementoplasty, histology, osteoconduction, osteoporosis, platelet-rich plasma, polymethyl methacrylate, vertebra

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Reduced Gap Strains Induce Changes in Bone Regeneration During Distraction

Journal of Biomechanical Engineering ◽

10.1115/1.2798331 ◽

1999 ◽

Vol 121 (3) ◽

pp. 348-355 ◽

Cited By ~ 10

Author(s):

M. Richards ◽

N. A. Waanders ◽

J. A. Weiss ◽

V. Bhatia ◽

L. E. Senunas ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Repair ◽

Volume Fraction ◽

Rabbit Model ◽

Zealand White Rabbit ◽

Limb Lengthening ◽

Bone Volume ◽

Bone Volume Fraction ◽

Trabecular Thickness ◽

Nutrient Delivery

A bilateral New Zealand white rabbit model of distraction osteogenesis (DO) was used to investigate the relationship between strain environment and bone regeneration during limb lengthening. In seven (n = 7) rabbits, a stiffener was applied to the fixator on one side to reduce strains within the gap tissue after lengthening was completed. Animals were euthanized six days later and their distraction zones were harvested and analyzed for changes in new bone volume and architecture. Nonlinear finite element analyses (FEA) were performed to predict changes in the gap strain environment. FEA results predicted a nearly uniform sevenfold decrease in average strain measures within the distraction zone. No change in total average new bone volume and significant decreases in both bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) were observed in tibiae in which gap strains were reduced experimentally, compared to contralateral controls. These results suggest that fixator stiffening influenced the architecture but not the amount of newly formed bone. This animal model of distraction might be used to study the mechanisms by which strain fields affect events in bone repair and regeneration, such as cell proliferation, precursor tissue differentiation, and altered growth factor and nutrient delivery to tissues.

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In Vivo Efficacy of Neutrophil-Mediated Bone Regeneration Using a Rabbit Calvarial Defect Model

International Journal of Molecular Sciences ◽

10.3390/ijms222313016 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13016

Author(s):

Thanuja D. K. Herath ◽

Leonardo Saigo ◽

Benoit Schaller ◽

Anis Larbi ◽

Swee Hin Teoh ◽

...

Keyword(s):

Bone Regeneration ◽

Volume Fraction ◽

Bone Defects ◽

Bone Volume ◽

Surgical Removal ◽

Calvarial Defect ◽

Bone Area ◽

Defect Model ◽

In Vivo Efficacy

Reconstruction of bone due to surgical removal or disease-related bony defects is a clinical challenge. It is known that the immune system exerts positive immunomodulatory effects on tissue repair and regeneration. In this study, we evaluated the in vivo efficacy of autologous neutrophils on bone regeneration using a rabbit calvarial defect model. Methods: Twelve rabbits, each with two surgically created calvarial bone defects (10 mm diameter), were randomly divided into two groups; (i) single application of neutrophils (SA-NP) vs. SA-NP control, and (ii) repetitive application of neutrophils (RA-NP) vs. RA-NP control. The animals were euthanized at 4 and 8 weeks post-operatively and the treatment outcomes were evaluated by micro-computed tomography, histology, and histomorphometric analyses. Results: The micro-CT analysis showed a significantly higher bone volume fraction (bone volume/total volume) in the neutrophil-treated groups, i.e., median interquartile range (IQR) SA-NP (18) and RA-NP (24), compared with the untreated controls, i.e., SA-NP (7) and RA-NP (14) at 4 weeks (p < 0.05). Similarly, new bone area fraction (bone area/total area) was significantly higher in neutrophil-treated groups at 4 weeks (p < 0.05). Both SA-NP and RA-NP had a considerably higher bone volume and bone area at 8 weeks, although the difference was not statistically significant. In addition, immunohistochemical analysis at 8 weeks revealed a higher expression of osteocalcin in both SA-NP and RA-NP groups. Conclusions: The present study provides first hand evidence that autologous neutrophils may have a positive effect on promoting new bone formation. Future studies should be performed with a larger sample size in non-human primate models. If proven feasible, this new promising strategy could bring clinical benefits for bone defects to the field of oral and maxillofacial surgery.

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Combinatorial Gene Therapy with BMP2/7 Enhances Cranial Bone Regeneration

Journal of Dental Research ◽

10.1177/154405910808700906 ◽

2008 ◽

Vol 87 (9) ◽

pp. 845-849 ◽

Cited By ~ 70

Author(s):

J.T. Koh ◽

Z. Zhao ◽

Z. Wang ◽

I.S. Lewis ◽

P.H. Krebsbach ◽

...

Keyword(s):

Gene Therapy ◽

Alkaline Phosphatase ◽

Bone Regeneration ◽

Volume Fraction ◽

Bone Volume ◽

Cranial Bone ◽

Bone Volume Fraction ◽

Stimulate Bone Formation ◽

Protein Levels ◽

Calvarial Defects

BMP2/7 heterodimer expression by adenovirus can stimulate bone formation at subcutaneous sites. In the present study, we evaluate whether this approach will also promote healing of cranial defects. Adenovirus expressing BMP2 or BMP7 (AdBMP2, AdBMP7) was titrated to yield equivalent BMP protein levels after transduction into murine BLK cells. Analysis of conditioned medium showed that BMP2/7 heterodimers have enhanced ability to stimulate alkaline phosphatase and Smad 1,5,8 phosphorylation relative to equivalent amounts of BMP2 or BMP7 homodimers. To measure bone regeneration, we implanted virally transduced BLK cells into critical-sized calvarial defects generated in C57BL6 mice. AdBMP2/7-transduced cells were more effective in healing cranial defects than were cells individually transduced with AdBMP2 or BMP7. Dramatic increases in bone volume fraction, as measured by microCT, as well as fusion of regenerated bone with the defect margins were noted. Thus, the use of gene therapy to express heterodimeric BMPs is a promising potential therapy for healing craniofacial bones.

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A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma

Seminars in Oncology ◽

10.1053/j.seminoncol.2020.02.012 ◽

2020 ◽

Vol 47 (6) ◽

pp. 398-408

Author(s):

Sonam Tulsyan ◽

Showket Hussain ◽

Balraj Mittal ◽

Sundeep Singh Saluja ◽

Pranay Tanwar ◽

...

Keyword(s):

Systematic Review ◽

Gallbladder Carcinoma ◽

In Silico ◽

In Silico Analysis ◽

Transcriptomic Profile ◽

Silico Analysis

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In Silico Analysis of Single Nucleotide Polymorphism in Human Prothrombin Gene

10.1055/s-0039-1680245 ◽

2019 ◽

Author(s):

I. Farah ◽

A. El-Mubark ◽

M. Osman ◽

A. Soliman ◽

F. Ali ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

In Silico ◽

In Silico Analysis ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Prothrombin Gene ◽

Silico Analysis

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Enalos Suite of Tools: Enhancing Cheminformatics and Nanoinfor - matics through KNIME

Current Medicinal Chemistry ◽

10.2174/0929867327666200727114410 ◽

2020 ◽

Vol 27 (38) ◽

pp. 6523-6535 ◽

Cited By ~ 3

Author(s):

Antreas Afantitis ◽

Andreas Tsoumanis ◽

Georgia Melagraki

Keyword(s):

Data Analysis ◽

Virtual Screening ◽

In Silico ◽

Model Development ◽

In Silico Analysis ◽

Material Design ◽

Efficient Solutions ◽

Biological Data ◽

Cost Efficient ◽

Silico Analysis

Drug discovery as well as (nano)material design projects demand the in silico analysis of large datasets of compounds with their corresponding properties/activities, as well as the retrieval and virtual screening of more structures in an effort to identify new potent hits. This is a demanding procedure for which various tools must be combined with different input and output formats. To automate the data analysis required we have developed the necessary tools to facilitate a variety of important tasks to construct workflows that will simplify the handling, processing and modeling of cheminformatics data and will provide time and cost efficient solutions, reproducible and easier to maintain. We therefore develop and present a toolbox of >25 processing modules, Enalos+ nodes, that provide very useful operations within KNIME platform for users interested in the nanoinformatics and cheminformatics analysis of chemical and biological data. With a user-friendly interface, Enalos+ Nodes provide a broad range of important functionalities including data mining and retrieval from large available databases and tools for robust and predictive model development and validation. Enalos+ Nodes are available through KNIME as add-ins and offer valuable tools for extracting useful information and analyzing experimental and virtual screening results in a chem- or nano- informatics framework. On top of that, in an effort to: (i) allow big data analysis through Enalos+ KNIME nodes, (ii) accelerate time demanding computations performed within Enalos+ KNIME nodes and (iii) propose new time and cost efficient nodes integrated within Enalos+ toolbox we have investigated and verified the advantage of GPU calculations within the Enalos+ nodes. Demonstration data sets, tutorial and educational videos allow the user to easily apprehend the functions of the nodes that can be applied for in silico analysis of data.

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In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

Current Proteomics ◽

10.2174/1570164616666190401204009 ◽

2020 ◽

Vol 17 (1) ◽

pp. 40-50

Author(s):

Farzane Kargar ◽

Amir Savardashtaki ◽

Mojtaba Mortazavi ◽

Masoud Torkzadeh Mahani ◽

Ali Mohammad Amani ◽

...

Keyword(s):

Phylogenetic Tree ◽

In Silico ◽

Alpha Helix ◽

In Silico Analysis ◽

Glycogen Storage ◽

Docking Studies ◽

Random Coil ◽

Special Topic ◽

Industrial Biotechnology ◽

In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

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