■ value obtained by TG analysis ♦ value obtained by gravimetric measurements

■ value obtained by TG analysis ♦ value obtained by gravimetric measurements

Fig. 21. Gravimetric variation of deposited HA with the number of deposited layers

The classical mineralization method conducted by dipping a collagen matrix in Ca(OH)2 suspension for 24 h followed by dipping the collagen matrix in NaH2PO4 solution for a further 24 h can be improved by using the LbL deposition method. Deposition of six HA layers obtained by alternately soaking in a Ca(OH)2 suspension for 20 min and then in a NaH2PO4 solution for 10 min resulted in a 12% increase in HA deposition. Extrapolating from the obtained results, it can be estimated that for a collagen matrix, such as the ones used in these experiments, one would need to deposit about 14 layers of HA to obtain a composite material similar to whale bone, while antler bone composition can be obtained if seven HA layers are deposited.

The obtained composite materials can be assumed to be hydroxyapatite matrices reinforced with mineralized collagen fibers as they have a structure very similar to the bone structure suggested by Hellmich et al. (Hellmich et al. 2004).

The good linearity of the quantity of deposited HA with respect to the number of layers is due to interactions occurring not only between collagen and HA, but also between deposited HA and Ca2+ ions.

From the parameters that influence the deposition of HA, we can distinguish three main categories: support dependent, solution/suspension dependent and processing parameters. While the first two categories have been extensively studied and can be quantified, the third category is very difficult to be quantified.

Under similar mineralization conditions, the amount of deposited HA is greater in the presence of citrate ions, but the LbL method applied to a pure collagen matrix can increase the amount of deposited HA even more than in the case of one layer deposition (24+24 h) onto citrate enriched collagen matrices.

5. The synthesis of complex COLL/HA+Fe3O4 composite materials

Magnetite is a mineral with multiple roles in both medical (Ito et al. 2005; Mornet et al. 2006; Zhang and Misra 2007) and non-medical applications (Ficai et al. 2010d; Ju and Bian 2006). The addition of magnetic nanoparticles (especially magnetite nanoparticles) induces new properties to the COLL/HA composite materials (Andronescu et al. 2010). The bone regenerative effects are due to the presence of COLL/HA while the anti-tumoral effects are due to the presence of magnetite which can produce hyperthermia when an electromagnetic field is applied. These systems, even at low magnetite concentration (5%) can be used for curative purpose because can generate the necessary hyperthermia and consequently induce tumoral cell apoptosis. It is important to mention that the presence of magnetite even at low concentration (1-2%) may induce hyperthermia but, in order to be useful for medical applications (hyperthermia - cancer treatment) at least 5% of magnetite is required. One of the most important advantage of the use of magnetite based composite materials is that hyperthermia can be activated only when is necessary and consequently the side effects is limited comparing with chemotherapy, for instance. As a matter of course these materials will be improved by the addition of other antitumoral agents such as silver or gold nanoparticles, cytostatics or other drugs for pain managements.

6. Conclusions

Collagen/hydroxyapatite composite materials are the most similar synthetic grafts with bone from many points of view, bone being composed from collagen and hydroxyapatite as main components and few percent of other components.

The morphology and subsequent the properties of the composite materials is strongly influenced by the presence of different components, even when they are present in small proportions. The reason that perfect bone graft materials have not been successfully synthesized is due to the limited number of components used in the synthesis of bone graft materials, which typically include only collagen and hydroxyapatite or carbonated apatite. It is worth to mention that all commercially available collagen forms can be converted into COLL/HA composite materials with dense or spongious microstructure. If collagen gel can be easily converted in dense or spongious materials by a proper choice of the drying method, collagen

Similar with compact bone

Fig. 22. The influence of collagen form on the composite materials microstructure

Based on the presented results, it can be concluded that the presence of additional components (which are usually found in natural bone in small concentrations) is of significant importance. For instance, the presence of fluoride induces a higher crystallinity in the deposited mineral phase. The morphology of the apatite phase was found to be lamellar by SEM, where visible pores were not observed, even at relatively high magnification.

Similar with spongy bone

The shape of the mineral phase of the composite material obtained by in vitro co-precipitation in the presence of fluoride is biomimetic and similar to the mineral phase of natural bone. The main difference between the mineral phases of bone and composite materials obtained in the presence of F- is the size of the crystal. In order to obtain natural-sized crystals in the mineral phase, crystallization inhibitors may be used. Under these conditions, we expect to reduce the size of the crystals.

Not only the presence of different components can induce morpho-structural modifications but also the synthesis route. For instance, the proper, applied electric or magnetic field or the drying method corroborated with ionic strength and pH lead to the formation of highly oriented COLL/HA composite materials. The synthesis of COLL/HA composite materials with oriented morphology of the mineralized collagen fibrils and fibres is an essential step to obtain bone grafts of the long bones. The orientation degree, based on SEM images, was of great importance and allows the quantification of the orientation. Based on the existing data, best orientation can achieve with self-assembling, the mean orientation degree being of ~ 97%.

7. Aknowledgements

Authors recognize financial support from the European Social Fund through POSDRU/89/1.5/S/54785 project: "Postdoctoral Program for Advanced Research in the field of nanomaterials and from Romanian Authority for Scientific Research through the project 72-198. We also thank to Elsevier for the amability to reuse some parts of text or figures.

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