Functionalization of microstructured open-porous bioceramic scaffolds with human fetal bone cells.

Bone substitute materials allowing trans-scaffold migration and in-scaffold survival of human bone-derived cells are mandatory for development of cell-engineered permanent implants to repair bone defects. In this study, we evaluated the influence on human bone-derived cells of the material composition and microstructure of foam scaffolds of calcium aluminate. The scaffolds were prepared using a direct foaming method allowing wide-range tailoring of the microstructure for pore size and pore openings. Human fetal osteoblasts (osteo-progenitors) attached to the scaffolds, migrated across the entire bioceramic depending on the scaffold pore size, colonized, and survived in the porous material for at least 6 weeks. The long-term biocompatibility of the scaffold material for human bone-derived cells was evidenced by in-scaffold determination of cell metabolic activity using a modified MTT assay, a repeated WST-1 assay, and scanning electron microscopy. Finally, we demonstrated that the osteo-progenitors can be covalently bound to the scaffolds using biocompatible click chemistry, thus enhancing the rapid adhesion of the cells to the scaffolds. Therefore, the different microstructures of the foams influenced the migratory potential of the cells, but not cell viability. Scaffolds allow covalent biocompatible chemical binding of the cells to the materials, either localized or widespread integration of the scaffolds for cell-engineered implants.

A straightforward, one-pot protocol for the synthesis of fused 3-aminotriazoles.

A simple protocol for the synthesis of 3-amino-[1,2,4]triazolo[4,3-a]pyridines is reported. The newly developed one-pot methodology involves the reaction of hydrazinopyridine with isothiocyanates to give the corresponding thiosemicarbazides, which are further desulfurized in situ using polymer-supported Mukaiyama's reagent to promote the final cyclization and formation of the central core. Aryl isothiocyanates bearing both electron-donating and electron-withdrawing groups are well tolerated, and the expected compounds were obtained in excellent purities and yields after removal of salts with a SPE-NH2 column. This methodology proved to be robust in the extension to 3-amino-[1,2,4]triazolo[4,3-a]-pyrazines and 3-amino-[1,2,4]triazolo[4,3-c]-pyrimidines, and no significant differences were noticed in terms of purities and yields. The straightforward protocol developed, mix, filter, and evaporate, is appropriate for performing multiple reactions in parallel fashion without need of purification.

Chemical functionalization of bioceramics to enhance endothelial cells adhesion for tissue engineering.

To control the selective adhesion of human endothelial cells and human serum proteins to bioceramics of different compositions, a multifunctional ligand containing a cyclic arginine-glycine-aspartate (RGD) peptide, a tetraethylene glycol spacer, and a gallate moiety was designed, synthesized, and characterized. The binding of this ligand to alumina-based, hydroxyapatite-based, and calcium phosphate-based bioceramics was demonstrated. The conjugation of this ligand to the bioceramics induced a decrease in the nonselective and integrin-selective binding of human serum proteins, whereas the binding and adhesion of human endothelial cells was enhanced, dependent on the particular bioceramics.

Surface functionalization of alumina ceramic foams with organic ligands.

Different anchoring groups have been studied with the aim of covalently binding organic linkers to the surface of alumina ceramic foams. The results suggested that a higher degree of functionalization was achieved with a pyrogallol derivative--as compared to its catechol analogue--based on the XPS analysis of the ceramic surface. The conjugation of organic ligands to the surface of these alumina materials was corroborated by DNP-MAS NMR measurements.