Regulation of osteogenesis and angiogenesis by cobalt, manganese and strontium doped apatitic materials for functional bone tissue regeneration.

Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO4·2H2O (DCPD) and tetracalcium phosphate, Ca4(PO4)2O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption.

Anti-Oxidant Multi-Functionalized Materials: Strontium-Substituted Monetite and Brushite as Delivery Systems for Curcumin.

Curcumin has numerous biological activities and pharmaceutical applications related to its ability to inhibit reactive oxygen species. Herein, strontium-substituted monetite (SrDCPA) and strontium-substituted brushite (SrDCPD) were synthesized and further functionalized with curcumin with the aim to develop materials that combine the anti-oxidant properties of the polyphenol, the beneficial role of strontium toward bone tissue, and the bioactivity of calcium phosphates. Adsorption from hydroalcoholic solution increases with time and curcumin concentration, up to about 5-6 wt%, without affecting the crystal structure, morphology, and mechanical response of the substrates. The multi-functionalized substrates exhibit a relevant radical scavenging activity and a sustained release in phosphate buffer. Cell viability, morphology, and expression of the most representative genes were tested for osteoclast seeded in direct contact with the materials and for osteoblast/osteoclast co-cultures. The materials at relatively low curcumin content (2-3 wt%) maintain inhibitory effects on osteoclasts and support the colonization and viability of osteoblasts. The expressions of Alkaline Phosphatase (ALPL), collagen type I alpha 1 chain (COL1A1), and osteocalcin (BGLAP) suggest that curcumin reduces the osteoblast differentiation state but yields encouraging osteoprotegerin/receptor activator for the NFkB factor ligand (OPG/RANKL) ratio.

Hydroxyapatite Decorated with Tungsten Oxide Nanoparticles: New Composite Materials against Bacterial Growth.

The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO3) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO3 nanoparticles. The number of nanoparticles loaded on the substrates was determined through Molecular Plasma-Atomic Emission Spectroscopy and is quite small, so it cannot be detected through X-ray diffraction analysis. It increases from HAPAA, to HA, to HAPEI, in agreement with the different values of zeta potential of the different substrates. HRTEM and STEM images show the dimensions of the nanoparticles are very small, less than 1 nm. In physiological solution HA support displays a greater tungsten cumulative release than HAPEI, despite its smaller loaded amount. Indeed, WO3 nanoparticles-functionalized HA exhibits a remarkable antibacterial activity against the Gram-positive Staphylococcus aureus in absence of cytotoxicity, which could be usefully exploited in the biomedical field.