Vitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: Synthesis, characterization and biological evaluation.

The development of new drugs for musculoskeletal regeneration purposes has attracted much attention in the last decades. In this work, we present three novel vitamin B9 (folic acid)-derivatives bearing divalent cations (ZnFO, MgFO and MnFO), providing their synthesis mechanism and physicochemical characterization. In addition, a strong emphasis has been placed on evaluating their biological properties (along with our previously reported SrFO) using human mesenchymal stem cells (hMSC). In all the cases, pure folate derivatives (MFOs) with a bidentate coordination mode between the metal and the folate anion, and a 1:1 stoichiometry, were obtained in high yields. A non-cytotoxic dose of all the MFOs (50 µg/mL) was demonstrated to modulate by their own the mRNA profiles towards osteogenic-like or fibrocartilaginous-like phenotypes in basal conditions. Moreover, ZnFO increased the alkaline phosphatase activity in basal conditions, while both ZnFO and MnFO increased the matrix mineralization degree in osteoinductive conditions. Thus, we have demonstrated the bioactivity of these novel compounds and the suitability to further studied them in vivo for musculoskeletal regeneration applications.

Development of Composite Scaffolds Based on Cerium Doped-Hydroxyapatite and Natural Gums-Biological and Mechanical Properties.

Hydroxyapatite (HAp) is a ceramic material composing the inorganic portion of bones. Ionic substitutions enhance characteristics of HAp, for example, calcium ions (Ca2+) by cerium ions (Ce3+). The use of HAp is potentialized through biopolymers, cashew gum (CG), and gellan gum (GG), since CG/GG is structuring agents in the modeling of structured biocomposites, scaffolds. Ce-HApCG biocomposite was synthesized using a chemical precipitation method. The obtained material was frozen (-20 °C for 24 h), and then vacuum dried for 24 h. The Ce-HApCG was characterized by X-Ray diffractograms (XRD), X-ray photoemission spectra (XPS), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), and energy dispersive spectroscopy (EDS). XRD and FTIR showed that Ce-HApCG was successfully synthesized. XRD showed characteristic peaks at 2θ = 25.87 and 32.05, corresponding to the crystalline planes (0 0 2) and (2 1 1), respectively, while phosphate bands were present at 1050 cm-1 and 1098 cm-1, indicating the success of composite synthesis. FESEM showed pores and incorporated nanostructured granules of Ce-HApCG. The mechanical test identified that Ce-HApCG has a compressive strength similar to the cancellous bone's strength and some allografts used in surgical procedures. In vitro tests (MTT assay and hemolysis) showed that scaffold was non-toxic and exhibited low hemolytic activity. Thus, the Ce-HApCG has potential for application in bone tissue engineering.