Improving surface and transport properties of macroporous hydrogels for bone regeneration

Abstract

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.

Design and characterization of an in vivo injectable hydrogel with effervescently generated porosity for regenerative medicine applications

“…The induction of porosity inside injectable hydrogels is therefore critical for regenerative purposes. A variety of techniques such as electrospinning [11], freeze drying [12,13], gas/salt leaching [14,15], emulsion templating [16,17], phase separation [18] or gas foaming techniques using CO 2 [19][20][21][22][23][24] have been proposed to induce a porous structure inside hydrogels. However, even though these approaches are interesting, they are not suitable with direct injection due to mandatory production steps beforehand or to the use of harsh solvents.…”

Laser‐Assisted Fabrication of Injectable Nanofibrous Cell Carriers

“…[ 19 ] The hydrophilic network of a hydrogel with large interconnected pores enables an efficient cell infiltration and the fast diffusion of oxygen, nutrients, and signaling molecules. [ 20 ] Alternatively, injectable scaffolds can be designed by using shear‐thinning hydrogels or polymer blends. In these systems, viscosity decreases when shear strain is increased, allowing the hydrogel to flow during the injection.…”

Polysaccharide-based scaffold for tissue-regeneration

“…Moreover, in the field of bone tissue engineering, we find alginate as a possible component of biomaterials. In most cases, alginate is used in the form of hydrogel, which has multiple benefits: mechanical stability, satisfying degradability, possibility to repair irregular shape defects due to its capability to cross-link in situ, through minimally invasive surgery [54,55] and its use as drug career for therapeutic controlled release. The crucial point about the use of alginate-based hydrogels for bone regeneration is the formation of hydroxyapatite [56], so most of the studies present in the literature incorporate inside the polymeric matrices salt crystals or other inorganic minerals.…”