Improving surface and transport properties of macroporous hydrogels for bone regeneration

Hydrogels have been frequently considered as suitable materials for hard tissue engineering as mineralized extracellular matrix analogue. However, major lacks in bone-substitution still concern the mimicking of native microenvironment for promoting cell differentiation into osteogenic way. Here, we propose the study of mineralized macroporous hydrogels (mMHs) made of poly(ethylenglycol)diacrylate fabricated by the combination of ultraviolet photopolymerization/salt leaching technique and treated by osteopromotive medium. We demonstrate that peculiar morphological and chemical features of mMH are crucial to create a reservoir system able to efficiently recruit environmental signals to cells. In particular, mass transport mechanisms are regulated by the coupling of a Knudsen-type diffusion within the void space of the pores with a standard diffusion mechanism through the pores walls. Meanwhile, the deposition of hydrophilic mineral phases onto the pore surface further affects transport mechanisms, in view of their capability to establish interactions with water molecules and to exert mechanical constrains on the swelling of the hydrogel network, thus promoting slower diffusion kinetics. These properties concur to influence in vitro human mesenchymal stem cells activities: macropore architecture of the hydrogel-like network positively affects cell recognition as compared to nonporous scaffolds, while osteopromotive treatment mainly allows to guide differentiation in osteogenic way as proved by staining of in vitro formed Ca-rich mineral deposits (i.e., alizarin red) and expression via reverse transcription-polymerase chain reaction of main bone markers. Hence, mMH is promising to develop three-dimensional scaffolds as experimental model to study in vitro cell events during bone regeneration.