This study was undertaken to understand the biodegradation mechanisms of calcium phosphate (Ca-P) biomaterials with different crystallization. Two types of sintered Ca-P porous ceramic (HA and beta-TCP) and a Ca-P bone cement (CPC) were implanted into cavities drilled in rabbit femoral and tibiae condyles. The results have shown that a material biodegradation was rapid in the beta-TCP and the CPC, but very weak in the HA. This biodegradation presented a decrease of material volume from the periphery to the center as well as a particle formation causing phagocytosis by numerous macrophages and multinucleated giant cells in the CPC. In the beta-TCP, there was a peripheral and central decrease of material volume as well as an absence of particle formation or visible phagocytosis. The process of biodegradation is considered to be directly influenced by the type of material crystallization. The sintered bioceramics processed at a high temperature exhibit good crystallization and are primarily degraded by a process dependent on interstitial liquids. However, the bone cement is formed by physicochemical crystallization and is degraded through a dissolution process associated with a cellular process.

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The influence of three well-known disaccharides, namely, trehalose, maltose, and sucrose, on some structural and dynamical properties of lysozyme has been investigated by means of molecular dynamics computer simulations in the 37-60 wt % concentration range. The effects of sugars on the protein conformation are found to be relatively weak, in agreement with the preferential hydration of lysozyme. Conversely, sugars seem to increase significantly the relaxation times of the protein. These effects are shown to be correlated to the fractional solvent accessibilities of lysozyme residues and further support the slaving of protein dynamics. Moreover, a significant increase in the relaxation times of lysozyme, sugars, and water molecules is observed within the studied concentration range and may result from the percolation of the hydrogen-bond network of sugar molecules. This percolation appears to be of primary importance to explain the influence of sugars on the dynamical properties of lysozyme and water.

A systematic study of three well-known bioprotectant sugars -trehalose, sucrose and maltose-in water solutions has been performed at different concentrations and temperatures using molecular-dynamics simulations. A variety of relevant probes such as the size of hydrogen-bonded water clusters, the orientational order parameter q, the Voronoi volume and the dynamical structure factor have been determined to describe the effect of the three disaccharides on water quantitatively. This investigation points out different structural and dynamical behaviours for which a threshold concentration φA and a crossover temperature TA emerge. A "destructuring" effect on the water network and a slowing-down of its dynamics are highlighted. These results suggest narrow links between the different scenarios tentatively explaining bioprotection.

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The interconnections in a porous biomaterial are the pathways between the pores. They conduct cells and vessels between pores. Thus they favour bone ingrowth inside ceramics. The aim of our study was to determine the effect on bone ingrowth of interconnections in two ceramics: hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) with the same porosity of about 50% and a mean pores size of 100-300 microm and a mean interconnection size of 30-100 microm. In vitro, four discs for osteoblast culture were studied after 14 and 28 days of incubation. The results show that human osteoblasts can penetrate interconnections over 20 microm in size, and colonize and proliferate inside macropores, but the most favourable size is over 40 microm. In vivo, eight cylinders were implanted in the middle shaft of both rabbit femurs for 12 or 24 weeks. The histomorphometric results show that interconnections in porous ceramics favour bone ingrowth inside the macropores. In the HA group the rate of calcification and bone ingrowth do not differ, and chondroid tissue is observed inside pores. But in beta-TCP, the calcification rate and the bone ingrowth increased significantly. At week 12 significant correlation between new bone ingrowth and the size of the interconnections is observed between new bone ingrowth and the density of pores. In conclusion we notice that in vivo a 20 microm interconnection size only allows cell penetration and chondroid tissue formation; however the size of the interconnections must be over 50 microm to favour new bone ingrowth inside the pores. We propose the concept of "interconnection density" which expresses the quantity of links between pores of porous materials. It assures cell proliferation and differentiation with blood circulation and extracellular liquid exchange. In resorbable materials, pore density and interconnection density are more important than their size, contrary to unresorbable materials in which the sizes and the densities are equally important.

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