Evaluations of clinical-grade bone substitute-combined simvastatin carriers to enhance bone growth: In vitro and in vivo analyses

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.

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.


2003 ◽  
Vol 254-256 ◽  
pp. 185-188 ◽  
Author(s):  
Yong Keun Lee ◽  
J. Song ◽  
Hyun Ju Moon ◽  
Sang Bae Lee ◽  
Kwang Mahn Kim ◽  
...  

2007 ◽  
Vol 361-363 ◽  
pp. 39-42 ◽  
Author(s):  
Serge Baroth ◽  
Xavier Bourges ◽  
Borhane H. Fellah ◽  
G. Daculsi

The purpose of this study ass to investigate the addition of round 80-200m granules shape radiopaque agents (RA) to synthetic Injectable Bone Substitute to improve contrast performance for minimal invasive surgery MIS. Composites were obtained by mixing BaSO4, Bi2O3, Lu2O3 or GdPO4 with calcium deficient apatite CDA which decompose during sintering process in BCP (60% HA, 40% β-TCP). Each composite was characterized: by XRD, FTIR. Biocompatibility was tested in vitro and in vivo in bony site (3 weeks implantation in rats). Primary results show that the suitable radiopaque BCP/RA composite (radiopacity intensity, biological responses) appeared to be BCP/Ba. Next works will complete the current studies on biological performance in association with different kind of resorbable injectable bone substitute as suspension, gel or calcium phosphate cements.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sajad Bahrami ◽  
Nafiseh Baheiraei ◽  
Mostafa Shahrezaee

AbstractA variety of bone-related diseases and injures and limitations of traditional regeneration methods require new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implantation in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds, and we evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, and the mechanical and chemical properties of scaffolds were characterized, showing three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. The rGO coating enhanced the mechanical strength of Col-rGO scaffolds to a greater extent than Col scaffolds by 2.8 times. Furthermore, Col-rGO scaffolds confirmed that graphene addition induced no cytotoxic effects and enhanced the viability and proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs) with 3D adherence and expansion. Finally, scaffold implantation into rabbit cranial bone defects for 12 weeks showed increased bone formation, confirmed by Hematoxylin–Eosin (H&E) and alizarin red staining. Overall, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.


Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2252
Author(s):  
Jae Eun Kim ◽  
Sangbae Park ◽  
Woong-Sup Lee ◽  
Jinsub Han ◽  
Jae Woon Lim ◽  
...  

The use of bone graft materials is required for the treatment of bone defects damaged beyond the critical defect; therefore, injectable calcium phosphate cement (CPC) is actively used after surgery. The application of various polymers to improve injectability, mechanical strength, and biological function of injection-type CPC is encouraged. We previously developed a chitosan–PEG conjugate (CS/PEG) by a sulfur (VI) fluoride exchange reaction, and the resulting chitosan derivative showed high solubility at a neutral pH. We have demonstrated the CPC incorporated with a poly (ethylene glycol) (PEG)-grafted chitosan (CS/PEG) and developed CS/PEG CPC. The characterization of CS/PEG CPC was conducted using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The initial properties of CS/PEG CPCs, such as the pH, porosity, mechanical strength, zeta potential, and in vitro biocompatibility using the WST-1 assay, were also investigated. Moreover, osteocompatibility of CS/PEG CPCs was carried out via Alizarin Red S staining, immunocytochemistry, and Western blot analysis. CS/PEG CPC has enhanced mechanical strength compared to CPC, and the cohesion test also demonstrated in vivo stability. Furthermore, we determined whether CS/PEG CPC is a suitable candidate for promoting the osteogenic ability of Dental Pulp Stem Cells (DPSC). The elution of CS/PEG CPC entraps more calcium ion than CPC, as confirmed through the zeta potential test. Accordingly, the ion trapping effect of CS/PEG is considered to have played a role in promoting osteogenic differentiation of DPSCs. The results strongly suggested that CS/PEG could be used as suitable additives for improving osteogenic induction of bone substitute materials.


2015 ◽  
Vol 5 (4) ◽  
pp. 457-466 ◽  
Author(s):  
Tianxing Gong ◽  
Zhiqin Wang ◽  
Yixi Zhang ◽  
Yubiao Zhang ◽  
Mingxiao Hou ◽  
...  

2009 ◽  
Vol 631-632 ◽  
pp. 211-216 ◽  
Author(s):  
Kyosuke Ueda ◽  
Takayuki Narushima ◽  
Takashi Goto ◽  
T. Katsube ◽  
Hironobu Nakagawa ◽  
...  

Calcium phosphate coating films were fabricated on Ti-6Al-4V plates and screw-type implants with a blast-treated surface using radiofrequency (RF) magnetron sputtering and were evaluated in vitro and in vivo. Amorphous calcium phosphate (ACP) and oxyapatite (OAp) films obtained in this study could cover the blast-treated substrate very efficiently, maintaining the surface roughness. For the in vitro evaluations of the calcium phosphate coating films, bonding strength and alkaline phosphatase (ALP) activity were examined. The bonding strength of the coating films to a blast-treated substrate exceeded 60 MPa, independent of film phases except for the film after post-heat-treatment in silica ampoule. When compared with an uncoated substrate, the increase in the ALP activity of osteoblastic SaOS-2 cells on a calcium phosphate coated substrate was confirmed by a cell culture test. The removal torque of screw-type Ti-6Al-4V implants with a blast-treated surface from the femur of Japanese white rabbit increased with the duration of implantation and it was statistically improved by coating an ACP film 2 weeks after implantation. The in vitro and in vivo studies suggested that the application of the sputtered ACP film as a coating on titanium implants was effective in improving their biocompatibility with bones.


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