Preparation And Properties Of Calcium Phosphate Cement Incorporated With Naturally-derived Active Substances

Calcium phosphate cement(CPC)is regarded as the ideal bone substitute material due to its excellent plasticity,mechanical property,biodegradability and biocompatibility.CPC is suitable for drug delivery as the carrier towing to its low temperature hydration and large intrinsic porosity.In this study,the naturally-derived active substances,including L-lysine(Lys),chondroitin sulfate(CS)and phosphatidylserine(PS),were added into CPC matrix,respectively.Physicochemical properties,including phase components,micromorphology,microstructure,mechanical strength,setting time and open porosity,of hydrated CPC were investigated.Effects of the CPC incorporated with active substances on the cellular adhesion,proliferation and osteogenic differentiation in vitro were further studied,and corresponding mechanisms of the cellular behaviors regulated by these active substances were unraveled.Lysine-loaded CPC was prepared by the addition of L-lysine in the liquid phase,and corresponding physicochemical properties and cytological evaluation of hydrated cement products were investigated.Compared with control CPC,lysine-loaded CPC revealed better cellular affinities and osteogenic differentiation capability.Moreover,these cellular behaviors regulated by the lysine-loaded CPC were dose-dependent for lysine.The results indicated that the incorporation of lysine hardly affected the phase components and microstructure of hydrated cement products.With the increase of the contents of lysine,the setting time of the cement pastes was slightly and gradually prolonged,while the compressive strength of hydrated cement products was enhanced.CS was dissolved in the liquid phase and successfully incorporated into CPC.Cellular affinities,proliferation and osteogenic differentiation of mBMSCs cultured on the hydrated cement products,CS-loaded CPC,were significantly enhanced compared with the control sample.Phase compositions,micromorphology,mechanical strength and porosity of the hydrated cement products were not significantly affected by the additive CS.The adsorption of CS molecules on the surface of raw particles could inhibit the cement hydration and prolong the setting time of cement pastes.PS/PLGA porous microspheres were prepared with emulsion-solvent evaporation method.With the increase of the content of PS,the hydrophilicity of PS/PLGA microspheres increased significantly.PS/PLGA porous microspheres were introduced into the cement matrix for the incorporation of bioactive PS and higher biodegradability of CPC.Compared with control PLGA/CPC composite,PS/PLGA/CPC composites showed better affinities and promoted osteogenic differentiation capacities of BMSCs.