Papers by Keyword: Osteoinduction

Abstract: This paper reports on the research into multiphase bone substitutes carried out by laboratories from the ‘Pays de la Loire’ region in France. This collaborative research was funded by both the French Government and the Regional Council in the period 2000-2007. Calcium phosphate bioceramics, polymers and combinations have been developed as bone substitutes for various maxillofacial and orthopaedic applications. These bone substitutes should support and regenerate bone tissue and resorb after implantation. In the bone tissue engineering area, they have been combined with autologous bone marrow cells or bioactive factors. The bone substitutes were tested in various animal models mimicking clinical situations or under pathological conditions (osteoporosis). In order to complete our research, the multiphase materials were also evaluated in clinical trials.

Abstract: The purpose of this study is to explore the osteoinductivity of the composite materials (calcium phosphate ceramics/PLA or collagen composites) with similar physical character of osteoinductive calcium phosphate ceramics and the influence of the chemical composition of the composite materials on osteoinductivity, and also to provide an experimental evidence for optimizing the design of the composite materials. Two kinds of composite materials were prepared. One (BCP/PLA) is fabricated with different ratio of BCP (biphasic calcium phosphate) ceramics powder and PDLLA powder through the particulateleaching technique. The other (BCP/collagen) is that BCP ceramics sintered at 1250oC and modified with collagen. The porous materials cylinders with Φ 5×8 mm were prepared. SEM was used to observe the microstructure and physical morphology of the composite materials. The two groups of composite materials cylinders were implanted in the dorsal muscles of four dogs. Six samples of each group were implanted in each dog respectively. The specimens were harvested at 2, 4, 12 and 24 weeks post operation, and thin decalcified sections were prepared for light microscopy (LM) analysis to evaluate their osteoinductivity and compare the capability of osteoinduction. The fibro-tissue and bone-like tissue were observed in the two composites, but no obvious bone formation was found in the tested periods. The results indicated that the composite materials could modify the mechanical property of ceramics. However, if the composite materials were biodegraded soon, new bone could not form into the scaffold, and the calcium phosphate should be the major component of osteoinductive materials.

Abstract: The purpose of this study was to evaluate the effect of HA/TCP biphasic ceramic on osteoinduction. HA/TCP ceramic cylinders with Φ8mm*10mm were prepared. The cylinder materials were stained by the calcein and alizarin red respectively, which were implanted into pigs’ dorsal muscle. The samples were harvested at 1, 2 and 3 month post-implantation. At 3 month post-implantation, the new bone tissues were observed in the inner pores of cylinders, which were stained by calcein or alizarin red at the same time, it was also found that the osteoblast in the margin of new bony tissue were stained by calcein and alizarin red. This result indicated that HA/TCP biphasic ceramic are osteoinductive in muscles of pigs, and participate in the process of new bone formation and calcification.

Abstract: The mRNA expression of Cbfa1 and osteocalcin gene induced by calcium phosphate ceramics (Ca/P) were quantitative analyzed according to real-time RT-PCR method in this work. C2C12 cells were co-culture with four kinds of porous Ca/P ceramics for 2 and 5d without adding other growth factors. The four kinds of Ca/P ceramics were pure hydroxyapatite (HA) sintered at 1250°C and HA/TCP with a ratio of 60/40 sintered at 1100°C (HT1), 1200°C (HT2) and 1250°C (HT3) respectively. Real-time RT-PCR analysis found the Ca/P ceramics induced positive expression of Cbfa1 and osteocalcin in C2C12 cells, After 5 days culture, Cbfa1 and osteocalcin showed obvious higher expression compared with that in 2 days. Cbfa1 and osteocalcin expression in BCP was much higher than HA, and the expression level of osteocalcin was HT1>HT2>HT3>HA. Our results showed that Ca/P ceramics alone were sufficient to induce C2C12 cells to osteoblastic differentiation and the sinter temperature and phase composition of Ca/P ceramics could affect their osteoindctive capacity significantly.

Abstract: Autologous bone chips are widely used in orthopedic surgery to fill large defects due to osteoinductive property but are limited in quantity. Several groups have reported the formation of mineralized bone after implantation of bioceramics in ectopic sites of different animals. However, osteoinduction by bioceramics has not yet proved to be equivalent to those of autologous bone. In this study, we compare the bone inducing capability of autologous bone chips and synthetic biphasic calcium phosphate (BCP) ceramics granules sintered at various temperatures. Both materials were implanted in muscles and femurs of goats inside hollow containers for 6, 12 and 24 weeks and analyzed by histology. This study showed that bone tissue formed in contact with micro porous ceramics sintered at low temperature as well as autologous bone chips both in ectopic and intrafemoral sites of goats.

Abstract: Thick coatings of bone morphogenetic protein (BMP)-calcium phosphate nano-composite were prepared by a biomimetic process, in which substrates were immersed in modified simulated body fluid containing rh-BMP2 at room temperature and pressure. In vitro analyses showed that the calcium phosphate and BMP formed stable and uniform coating of composite on surface of substrate, and that the composite derive significant improvement in tissue formation, suggesting an osteoinductive bioactive surface.

Abstract: The aim of this study was to optimize the surface treatment and to accelerate the osteoinductivity of porous bioactive titanium implant. Previous studies have reported that sodium removal with hot water treatment converts sodium titanate on the surface of an alkali-treated titanium plate into titania with a specific structure, which has better bioactivity than sodium titanate. We developed a dilute hydrochloric acid (HCl) treatment for porous titanium, which removed sodium from the complexly shaped porous structure more effectively than conventional hot water treatment. Three types of surface treatments were applied: (a) alkali and heat treatment, (b) alkali, hot water, and heat treatment (conventional treatment), and (c) alkali, dilute HCl, hot water, and heat treatment (Na-free treatment). The osteoinductivity of the materials implanted in the back muscles of adult beagle dogs was examined at three, six, and twelve months. Na-free porous bioactive titanium exhibited the highest osteoinductivity, and bone formation was observed within three months. This study showed that sodium removal has a significant positive effect on the osteoinductivity of the porous bioactive titanium implant.

Abstract: Osteoinduction by biomaterials that initially do not contain bone morphogenetic proteins and other growth factors has been shown to be a real phenomenon by many investigators in the past two decades. Although it is well-known that a material needs to meet very specific requirements in terms of physico-chemical and structural properties in order to be osteoinductive, the underlying mechanism of osteoinduction is not fully unraveled yet. In the present study we investigated parameters which are of importance for the osteoinductive potential of biomaterials by comparing four biphasic calcium-phosphate and a carbonated apatite ceramic. The results showed that the presence of micropores, by which the specific surface area of a material is increased, is essential for the material’s osteoinductivity. However, if the surface area is too high, or material is too resorbable because of its chemical composition, the implant might degrade and lose its shape. In that case, ectopic bone formation does not occur, as a relatively stable surface is needed to facilitate new bone growth.

Abstract: Osteoinductive biomaterials are able of inducing bone formation at ectopic, i.e. extraskeletal implantation sites. It is, however, important to investigate whether osteoinductive biomaterials perform better when implanted orthotopically as well, in particular in clinically relevant criticalsized defects. In this study, an osteoinductive and a non-osteoinductive biphasic calcium-phosphate (BCP) ceramic were compared in a critical-sized iliac wing defect that allows for paired comparison. After 12 weeks of implantation in the critical-sized defect, the osteoinductive BCP1150 ceramic showed significantly more bone than the non-osteoinductive BCP1300 ceramic. In addition, the analysis of fluorochrome markers, which were administered to the animals 4, 6 and 8 weeks after implantation in order to visualize the bone growth dynamics, showed an earlier start of bone formation in BCP1150 as compared to BCP1300. Significantly better performance of osteoinductive ceramic in a critical-sized orthotopic defect in a large animal model in comparison to the non-osteoinductive ceramic suggests osteoinduction to be clinically relevant.

Abstract: Calcium phosphate (Ca-P) biomaterials have been proved to show osteoinductivity, however the affecting factors and mechanism are still unclear now. In this study, the surface characteristics of biphasic Ca-P ceramics (hydroxyapatite/tricalcium phosphate; HA/TCP) sintered at the distinct temperature were investigated and the mechanism of the osteoinductivity was discussed. The osteoinductivity of HA/TCP ceramics increased with decreasing the sintering temperature. The different surface micro-structure resulted from different sintering temperature includes phase composition, surface micro-structure, and surface potential. These characteristics should be the important factors affecting osteoinductivity.