Osteogenic Potential Using a Malleable, Biodegradable Composite Added Traditional Chinese Medicine: in vitro and in vivo Evaluations

2006 ◽  
Vol 34 (05) ◽  
pp. 873-886 ◽  
Author(s):  
Chun-Hsu Yao ◽  
Bai-Shuan Liu ◽  
Chau-Guey Liu ◽  
Yueh-Sheng Chen

The purpose of this investigation was to prepare and evaluate the feasibility and biocompatibility of a new composite as a large defect bone substitute. The new GTGG was mainly composed of tricalcium phosphate ceramic particles and glutaraldehyde crosslinked gelatin in which Gui-Lu-Jiao was added (a mixture of Cervi Colla Cornus and Colla Plastri Testudinis). In the in vitro study, rat's calvaria osteoblasts were used to study bone characteristics upon exposure to different concentrations of the Gui-Lu-Jiao solution. In the in vivo study, GTGG composites were implanted into the defects of calvarial bones in mature New Zealand rabbits to test their osteogenerative characteristics. As a result, we found that Gui-Lu-Jiao added to the culture could promote the proliferation of osteoblasts. In addition, GTGG could induce a large amount of new bone growth in the rabbit's calvarial bone defect. Therefore, the GTGG composite might be a potential bone substitute.

Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 2023
Author(s):  
Fabien Kawecki ◽  
Todd Galbraith ◽  
William P. Clafshenkel ◽  
Michel Fortin ◽  
François A. Auger ◽  
...  

In vitro prevascularization has the potential to address the challenge of maintaining cell viability at the core of engineered constructs, such as bone substitutes, and to improve the survival of tissue grafts by allowing quicker anastomosis to the host microvasculature. The self-assembly approach of tissue engineering allows the production of biomimetic bone-like tissue constructs including extracellular matrix and living human adipose-derived stromal/stem cells (hASCs) induced towards osteogenic differentiation. We hypothesized that the addition of endothelial cells could improve osteogenesis and biomineralization during the production of self-assembled human bone-like tissues using hASCs. Additionally, we postulated that these prevascularized constructs would consequently improve graft survival and bone repair of rat calvarial bone defects. This study shows that a dense capillary network spontaneously formed in vitro during tissue biofabrication after two weeks of maturation. Despite reductions in osteocalcin levels and hydroxyapatite formation in vitro in prevascularized bone-like tissues (35 days of culture), in vivo imaging of prevascularized constructs showed an improvement in cell survival without impeding bone healing after 12 weeks of implantation in a calvarial bone defect model (immunocompromised male rats), compared to their stromal counterparts. Globally, these findings establish our ability to engineer prevascularized bone-like tissues with improved functional properties.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Caliogna ◽  
Valentina Bina ◽  
Laura Botta ◽  
Francesco Maria Benazzo ◽  
Marta Medetti ◽  
...  

Abstract Spine degenerative conditions are becoming increasingly prevalent, affecting about 5.7% of the population in Europe, resulting in a significant reduction of life’s quality. Up to now, many materials have been used in manufacturing cage implants, used as graft substitutes, to achieve immediate and long-term spinal fixation. Particularly, titanium and its alloys are emerging as valuable candidates to develop new types of cages. The aim of this in vitro study was to evaluate the adhesion, proliferation and osteogenic differentiation of adipose derived mesenchymal stem cells (ASCs) seeded on trabecular titanium cages. ASCs adhered, proliferated and produced an abundant extracellular matrix during the 3 weeks of culture. In the presence of osteogenic medium, ASCs differentiated into osteoblast-like cells: the expression of typical bone genes, as well as the alkaline phosphatase activity, was statistically higher than in controls. Furthermore, the dispersive spectrometry microanalysis showed a marked increase of calcium level in cells grown in osteogenic medium. Plus, our preliminary data about osteoinduction suggest that this titanium implant has the potential to induce the ASCs to produce a secretome able to trigger a shift in the ASCs phenotype, possibly towards the osteogenic differentiation, as illustrated by the qRT-PCR and ALP biochemical assay results. The trabecular porous organization of these cages is rather similar to the cancellous bone structure, thus allowing the bone matrix to colonize it efficiently; for these reasons we can conclude that the architecture of this cage may play a role in modulating the osteoinductive capabilities of the implant, thus encouraging its engagement in in vivo studies for the treatment of spinal deformities and diseases.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hye Kyung Kim ◽  
Myung-Gyou Kim ◽  
Kang-Hyun Leem

The aim of this study was to compare the effectiveness of velvet antler (VA) from different sections for promoting longitudinal bone growth in growing rats. VA was divided into upper (VAU), middle (VAM), and basal sections (VAB). An in vivo study was performed to examine the effect on longitudinal bone growth in adolescent rats. In addition, in vitro osteogenic activities were examined using osteoblastic MG-63 cells. VA promoted longitudinal bone growth and height of the growth plate in adolescent rats. Bone morphogenetic protein-2 (BMP-2) in growth plate of VA group was highly expressed compared with control. The anabolic effect of VA on bone was further supported by in vitro study. VA enhanced the proliferation, differentiation, and mineralization of MG-63 cells. The mRNA expressions of osteogenic genes such as collagen, alkaline phosphatase, and osteocalcin were increased by VA treatment. These effects of in vivo and in vitro study were decreased from upper to basal sections of VA. In conclusion, VA treatment promotes longitudinal bone growth in growing rats through enhanced BMP-2 expression, osteogenic activities, and bone matrix gene expressions. In addition, present study provides evidence for the regional differences in the effectiveness of velvet antler for longitudinal bone growth.


2017 ◽  
Vol 33 (2) ◽  
pp. 160-177 ◽  
Author(s):  
Tien-Ching Lee ◽  
Yan-Hsiung Wang ◽  
Shih-Hao Huang ◽  
Chung-Hwan Chen ◽  
Mei-Ling Ho ◽  
...  

We demonstrated in a value-added study that the combination of calcium phosphate–based bone substitute (MaxiBone® bioceramics) and simvastatin/poly lactic- co-glycolic acid (SIMm) carriers which were fabricated by GMP pharmaceutical company and underwent our patterned double-emulsion technique can promote bone growth. The average size distribution of SIMm, the encapsulation efficacy, and the in vitro release profile of simvastatin in SIMm over 14 days were investigated in this study. Based on the results of Alizarin Red S staining and alkaline phosphatase activity, the released simvastatin of SIMm can effectively induce osteogenesis of bone marrow mesenchymal stem cells (D1 cells). In the non-union fracture model of animal study, the MaxiBone bioceramics group and MaxiBone bioceramics with SIMm group showed a significant increase in the percentages of new bone matrix compared with the control group and SIMm groups at the 8th and 10th weeks. Moreover, the MaxiBone bioceramics with SIMm group showed the strongest effect in new bone formation among these groups. We concluded that the calcium phosphate–based ceramics of MaxiBone combined with SIMm can accelerate osteogenic differentiation and bone growth in vitro and in vivo. Our results provide a proof of concept that SIMm can play as an osteoinductive material and the combination with bone substitutes with osteoconductive property effectively enhance bone growth, and this treatment is value added for clinical application, especially in the healing of large bone defects or non-union. Graphical abstract. The clinical-grade calcium phosphate–based bone substitute combined SIM/PLGA/HAp microspheres were fabricated by GMP pharmaceutical company to promote bone growth in bone defect model of mice.


2014 ◽  
Author(s):  
Ivo Dumic-Cule ◽  
Dunja Rogic ◽  
Damir Jezek ◽  
Lovorka Grgurevic ◽  
Slobodan Vukicevic

Author(s):  
Antoine Berbéri ◽  
Joseph Sabbagh ◽  
Rita Bou Assaf ◽  
Michella Ghassibe-Sabbagh ◽  
Fatima Al-Nemer ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elodie A. Pérès ◽  
Jérôme Toutain ◽  
Louis-Paul Paty ◽  
Didier Divoux ◽  
Méziane Ibazizène ◽  
...  

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.


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