scholarly journals Treatment of Critical-Size Femoral Bone Defects with Chitosan Scaffolds Produced by a Novel Process from Textile Engineering

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1015
Author(s):  
Bruno Zwingenberger ◽  
Corina Vater ◽  
Roland L. Bell ◽  
Julia Bolte ◽  
Elisabeth Mehnert ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Critical Size ◽  
Bone Allograft ◽  
Bone Defects ◽  
Lower Grade ◽  
Femoral Bone ◽  
Human Cancellous Bone ◽  
Human Telomerase

The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For in vitro investigations, scaffolds made of CHS, mineralized collagen (MCM), or human cancellous bone allograft (CBA) were seeded with human telomerase-immortalized mesenchymal stromal cells (hTERT-MSC), incubated for 14 days, and thereafter evaluated for proliferation and osteogenic differentiation. In vivo, CHS, MCM and CBA scaffolds were implanted into 5 mm critical-size femoral bone defects in rats. After 12 weeks, the volume of newly formed bone was determined by microcomputed tomography (µCT), while the degree of defect healing, as well as vascularization and the number of osteoblasts and osteoclasts, was evaluated histologically. In vitro, CHS scaffolds showed significantly higher osteogenic properties, whereas treatment with CHS, in vivo, led to a lower grade of bone-healing compared to CBA and MCM. While chitosan offers a completely new field of scaffold production by fibers, these scaffolds will have to be improved in the future, regarding mechanical stability and osteoconductivity.

Gene-modified BMSCs encapsulated with carboxymethyl cellulose facilitate osteogenesis in vitro and in vivo

2020 ◽  
pp. 088532822094803
Author(s):  
Shicong Zheng ◽  
Hanzheng Chen ◽  
Tingshuai Zhang ◽  
Yongchang Yao ◽  
Yi Chen ◽  
...  
Keyword(s):  
Carboxymethyl Cellulose ◽  
Critical Size ◽  
Bone Defects ◽  
Bone Mesenchymal Stem Cells ◽  
Mrna And Protein Expression ◽  
Osteogenic Protein ◽  
Over Time ◽  
Osteogenesis In Vitro

Critical size bone defects are one of the most serious complications in orthopedics due to the lack of effective osteogenesis treatment. We fabricated carboxymethyl cellulose with phenol moieties (CMC-ph) microcapsules loaded with gene-modified rat bone mesenchymal stem cells (rBMSCs) that secrete hBMP2 following doxycycline (DOX) induction. The results showed that the morphology of microcapsules was spherical, and their diameters have equally distributed in the range of 100–150 μm; the viability of rBMSCs was unchanged over time. Through real-time PCR and Western blot analyses, the rBMSCs in microcapsules were found to secrete hBMP2 and to have upregulated mRNA and protein expression of osteogenesis-related genes in vitro and in vivo. Furthermore, the in vivo results suggested that the group with the middle concentration of cells expressed the highest amount of osteogenic protein over time. In this study, we showed that gene-modified rBMSCs in CMC-ph microcapsules had good morphology and viability. The BMP2–BMSCs/CMC-Ph microcapsule system could upregulate osteogenic mRNA and protein in vitro and in vivo. Further analysis demonstrated that the medium concentration of cells had a suitable density for transplantation in nude mice. Therefore, BMP2–BMSCs/CMC-Ph microcapsule constructs have potential for bone regeneration in vivo.

Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted Toxin Complexed with Polyethylenimine

2020 ◽  
Vol 20 (4) ◽  
pp. 289-296
Author(s):  
Yuriy Khodarovich ◽  
Darya Rakhmaninova ◽  
German Kagarlitskiy ◽  
Anastasia Baryshnikova ◽  
Sergey Deyev
Keyword(s):  
Growth Retardation ◽  
Bystander Effect ◽  
Dna Encoding ◽  
Complex Preparation ◽  
Human Telomerase ◽  
Linear Polyethylenimine ◽  
Cag Promoter ◽  
Targeted Toxin

Background:: One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding toxins under the control of tumor-specific promoters. Methods:: Here, we used DNA plasmids encoding very potent anti-ERBB2 targeted toxin, driven by the human telomerase promoter or by the ubiquitous CAG promoter (pTERT-ETA and pCAG-ETA) and linear polyethylenimine to target cancer cells. Results:: We showed that the selectivity of cancer cell killing by the pTERT-ETA plasmid is highly dependent upon the method of preparation of DNA-polyethylenimine complexes. After adjustment of complex preparation protocol, cell lines with high activity of telomerase promoter can be selectively killed by transfection with the pTERT-ETA plasmid. We also showed that cells transfected with pTERT-ETA and pCAG-ETA plasmids do not exert any detectable bystander effect in vitro. Conclusion:: Despite this, three intratumoral injections of a plasmid-polyethylenimine complex resulted in substantial growth retardation of a poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor properties between DNA constructs with telomerase or CAG promoters in vivo.

scholarly journals Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

2011 ◽  
Vol 5 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Oliver D Schneider ◽  
Dirk Mohn ◽  
Roland Fuhrer ◽  
Karina Klein ◽  
Käthi Kämpf ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Bone Formation ◽  
Antimicrobial Properties ◽  
Drill Hole ◽  
Bone Defects ◽  
Long Bone ◽  
Minimal Amount ◽  
Cotton Wool

Background: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Materials and Methods: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Results: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. Conclusions: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

scholarly journals The Disruption of the β-Catenin/TCF-1/STAT3 Signaling Axis by 4-Acetylantroquinonol B Inhibits the Tumorigenesis and Cancer Stem-Cell-Like Properties of Glioblastoma Cells, In Vitro and In Vivo

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 491 ◽  
Author(s):  
Heng-Wei Liu ◽  
Yu-Kai Su ◽  
Oluwaseun Bamodu ◽  
Dueng-Yuan Hueng ◽  
Wei-Hwa Lee ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Migration And Invasion ◽  
Rank Test ◽  
Lower Grade ◽  
Aberrant Expression ◽  
Stat3 Signaling ◽  
Log Rank Test ◽  
Signaling Axis

Background: Glioblastoma (GBM), a malignant form of glioma, is characterized by resistance to therapy and poor prognosis. Accumulating evidence shows that the initiation, propagation, and recurrence of GBM is attributable to the presence of GBM stem cells (GBM-CSCs). Experimental approach: Herein, we investigated the effect of 4-Acetylantroquinonol B (4-AAQB), a bioactive isolate of Antrodia cinnamomea, on GBM cell viability, oncogenic, and CSCs-like activities. Results: We observed that aberrant expression of catenin is characteristic of GBM, compared to other glioma types (p = 0.0001, log-rank test = 475.2), and correlates with poor prognosis of GBM patients. Lower grade glioma and glioblastoma patients (n = 1152) with low catenin expression had 25% and 21.5% better overall survival than those with high catenin expression at the 5 and 10-year time-points, respectively (p = 3.57e-11, log-rank test = 43.8). Immunohistochemistry demonstrated that compared with adjacent non-tumor brain tissue, primary and recurrent GBM exhibited enhanced catenin expression (~10-fold, p < 0.001). Western blot analysis showed that 4-AAQB significantly downregulated β-catenin and dysregulated the catenin/LEF1/Stat3 signaling axis in U87MG and DBTRG-05MG cells, dose-dependently. 4-AAQB–induced downregulation of catenin positively correlated with reduced Sox2 and Oct4 nuclear expression in the cells. Furthermore, 4-AAQB markedly reduced the viability of U87MG and DBTRG-05MG cells with 48 h IC50 of 9.2 M and 12.5 M, respectively, effectively inhibited the nuclear catenin, limited the migration and invasion of GBM cells, with concurrent downregulation of catenin, vimentin, and slug; similarly, colony and tumorsphere formation was significantly attenuated with reduced expression of c-Myc and KLF4 proteins. Conclusions: Summarily, we show for the first time that 4-AAQB suppresses the tumor-promoting catenin/LEF1/Stat3 signaling, and inhibited CSCs-induced oncogenic activities in GBM in vitro, with in vivo validation; thus projecting 4-AAQB as a potent therapeutic agent for anti-GBM target therapy.

scholarly journals TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 141
Author(s):  
Yanbing Wang ◽  
Yiwu Chen ◽  
Chang Li ◽  
Zhiwei Xiao ◽  
Hongming Yuan ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Catalytic Core ◽  
Tert Promoter ◽  
Human Telomerase ◽  
Mutant Cells

Human telomerase is a specialized DNA polymerase whose catalytic core includes both TERT and human telomerase RNA (hTR). Telomerase in humans, which is silent in most somatic cells, is activated to maintain the telomere length (TEL) in various types of cancer cells, including melanoma. In the vast majority of tumor cells, the TERT promoter is mutated to promote proliferation and inhibit apoptosis. Here, we exploited NG-ABEmax to revert TERT -146 T to -146 C in melanoma, and successfully obtained TERT promoter revertant mutant cells. These TERT revertant mutant cells exhibited significant growth inhibition both in vitro and in vivo. Moreover, A375−146C/C cells exhibited telomere shortening and the downregulation of TERT at both the transcription and protein levels, and migration and invasion were inhibited. In addition, TERT promoter revertant mutation abrogated the inhibitory effect of mutant TERT on apoptosis via B-cell lymphoma 2 (Blc-2), ultimately leading to cell death. Collectively, the results of our work demonstrate that reverting mutations in the TERT promoter is a potential therapeutic option for melanoma.

scholarly journals Preliminary in Vivo Evaluation of Bone Healing in Critical Size Bone Defects Implanted with an Injectable Calcium Phosphate Bone Cement (Osteopaste)

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Che Nor Zarida Che Seman ◽  
Zamzuri Zakaria ◽  
Zunariah Buyong ◽  
Mohd Shukrimi Awang ◽  
Ahmad Razali Md Ralib @ Md Raghib
Keyword(s):  
Calcium Phosphate ◽  
Bone Cement ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Size ◽  
Healing Process ◽  
Bone Defects ◽  
Calcium Phosphate Bone Cement ◽  
Rabbit Tibia

Introduction: A novel injectable calcium phosphate bone cement (osteopaste) has been developed. Its potential application in orthopaedics as a filler of bone defects has been studied. The biomaterial was composed of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. The aim of the present study was to evaluate the healing process of osteopaste in rabbit tibia. Materials and method: The implantation procedure was carried out on thirty-nine of New Zealand white rabbits. The in vivo bone formation was investigated by either implanting the Osteopaste, Jectos or MIIG – X3 into a critical size defect (CSD) model in the proximal tibial metaphysis. CSD without treatment served as negative control. After 1 day, 6 and 12 weeks, the rabbits were euthanized, the bone were harvested and subjected for analysis. Results: Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. There was direct contact between osteopaste material and host bone. The new bone was seen bridging the defect. Conclusion: The result showed that Osteopaste could be a new promising biomaterial for bone repair and has a potential in bone tissue engineering.

scholarly journals The possibility of healing alveolar bone defects with simvastatin thermosensitive gel: in vitro/in vivo evaluation

2018 ◽  
Vol Volume 12 ◽  
pp. 1997-2003 ◽  
Author(s):  
Hong Ruan ◽  
Youcheng Yu ◽  
Xuehua Guo ◽  
Qian Jiang ◽  
Ying Luo
Keyword(s):  
Alveolar Bone ◽  
Bone Defects ◽  
In Vivo Evaluation ◽  
Thermosensitive Gel

Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds

2017 ◽  
Vol 97 (1) ◽  
pp. 68-76 ◽  
Author(s):  
H. Shao ◽  
M. Sun ◽  
F. Zhang ◽  
A. Liu ◽  
Y. He ◽  
...  
Keyword(s):  
Weight Loss ◽  
Alveolar Bone ◽  
Bone Defects ◽  
Linear Shrinkage ◽  
Tris Buffer ◽  
Bone Tissue Regeneration ◽  
3 Dimensional ◽  
Flexural Resistance

Implanting artificial biomaterial implants into alveolar bone defects with individual shape and appropriate mechanical strength is still a challenge. In this study, bioceramic scaffolds, which can precisely match the mandibular defects in macro and micro, were manufactured by the 3-dimensional (3D) printing technique according to the computed tomography (CT) image. To evaluate the stimulatory effect of the material substrate on bone tissue regeneration in situ in a rabbit mandibular alveolar bone defect model, implants made with the newly developed, mechanically strong ~10% Mg-substituted wollastonite (Ca90%Mg10%SiO3; CSi-Mg10) were fabricated, implanted into the bone defects, and compared with implants made with the typical Ca-phosphate and Ca-silicate porous bioceramics, such as β-tricalcium phosphate (TCP), wollastonite (CaSiO3; CSi), and bredigite (Bred). The initial physicochemical tests indicated that although the CSi-Mg10 scaffolds had the largest pore dimension, they had the lowest porosity mainly due to the significant linear shrinkage of the scaffolds during sintering. Compared with the sparingly dissolvable TCP scaffolds (~2% weight loss) and superfast dissolvable (in Tris buffer within 6 wk) pure CSi and Bred scaffolds (~12% and ~14% weight loss, respectively), the CSi-Mg10 exhibited a mild in vitro biodissolution and moderate weight loss of ~7%. In addition, the CSi-Mg10 scaffolds showed a considerable initial flexural strength (31 MPa) and maintained very high flexural resistance during soaking in Tris buffer. The in vivo results revealed that the CSi-Mg10 scaffolds have markedly higher osteogenic capability than those on the TCP, CSi, and Bred scaffolds after 16 wk. These results suggest a promising potential application of customized CSi-Mg10 3D robocast scaffolds in the clinic, especially for repair of alveolar bone defects.

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