Bio-inspired polymeric iron-doped hydroxyapatite microspheres as a tunable carrier of rhBMP-2.

Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release profiles. The comparison with hybrid non-magnetic and with non-mineralized microspheres highlights the role of nanocrystalline, nanosize mineral phases when they exhibit surface charged groups enabling the chemical linking with the growth factor and thus moderating the release kinetics. All the microspheres show excellent osteogenic ability with human mesenchymal stem cells whereas the hybrid mineralized ones show a slow and sustained release of rhBMP-2 along 14 days of soaking into cell culture medium with substantially bioactive effect, as reported by assay with C2C12 BRE-Luc cell line. It is also shown that the release extent can be modulated by the application of pulsed electromagnetic field, thus showing the potential of remote controlling the bioactivity of the new micro-devices which is promising for future application of hybrid biomimetic microspheres in precisely designed and personalized therapies.

Superparamagnetic hybrid microspheres affecting osteoblasts behaviour.

The present work describes biomimetic hybrid microspheres made of collagen type I-like peptide matrix (RCP) mineralised with Fe2+/Fe3+ doping hydroxyapatite (RCPFeHA) by a bio-inspired process. Superparamagnetic RCPFeHA microspheres are obtained by emulsification of the hybrid slurries in the presence of citrate ions, to achieve a biomimetic surface functionalisation improving the bioactivity and the dispersion ability in cell culture medium. A biological in vitro study correlates the osteoblast cells behaviour to calcium and iron ions released by the hybrid microspheres in culture media mimicking physiological or inflammatory environment, evidencing a clear triggering of cell activity and bio-resorption ability. In presence of the microspheres, the osteoblast cells maintain their typical morphology and no cell damage were detected, whereas also showing up-regulation of osteogenic markers. The ability of the hybrid microspheres to undergo bio-resorption and release bioactive ions in response to different environmental stimuli without harmful effects opens new perspectives in bone regeneration, as magnetically active bone substitute with potential ability of drug carrier and smart response in the presence of inflammatory states.