Multifunctional substitute hydroxyapatite

Principal investigators: Monica Sandri, Michele Iafisco, Anna Tampieri

Personnel involved: Elisabetta Campodoni, Margherita Montanari, Alessio Adamiano, Lorenzo Degli Esposti, Francesca Carella

Synthesis of biomimetic and bioactive nanostructured micro- and nano-powders based on calcium phosphates alone or combined with organic phases (e.g. proteins, polysaccharides, fatty acid or vegetable oils) through a biomineralization process allowing the mineral nanostructured particles growth on the organic molecules.

The base form of hydroxyapatite contains only calcium and phosphate ions and it is characterized by a high porosity crystalline lattice capable to host doping ions such as carbonate, magnesium, silicon, strontium, titanium, fluorine, iron, manganese, boosting the multi-functionality and multi-applicability of hydroxyapatite not only in regenerative medicine but also in cosmetics.

Different powders have been developed modulating composition, in term of nature and amount of doping ions and organic phase, microstructure as well as crystals size and morphology that can be exploited in many application fields, in particular:

  • Multi-substituted apatite containing iron and titanium ions as doping ions (TiFeHA) gives to the powder the sun-screen power. The reflectance index highlighted by this apatite is suitable to use it as booster of SPF in solar cream also preserving the organic components after UV exposition because no photocatalytic effects were detected. The synthesis of this hydroxyapatite is performed in presence of organic phase (oil, fatty acid, polysaccharides, proteins …) exploiting a biomineralization process where the crystal growth takes place in strict contact with organic phase that constrains its growth creating a hybrid micrometric and nanostructured powder. The advantages of this material are to avoid the whitening effect typical of highly protective solar creams, to confer a brown colouring due to iron doping ions and to improve the dispersion and homogenization in the cream formulation due to organic phase. This material avoids the use of titanium dioxide which can cause allergic reactions due to its photocatalytic effect which degrades the organic solar filter and generate free radical.
  • Apatite as filler in make-up. Modifying the morphology of hydroxyapatite, a suitable sensoriality can be obtained to use it as filler in cosmetics. It can be used to replace zinc oxide or titanium oxide that induce allergic reaction or to the formulations addressed to the treatment of skin discolorations to obtain a skin colour more homogeneous and/or lighter. Finally, these powder can be functionalized with biocompatible and hydrosoluble organic molecules such as proteins, polysaccharides, PEGs through biomimetic processes to use these as volumizing fillers.
  • Bioactive apatite for the skin revitalization. Hydroxyapatite can be nucleated on collagen fibers obtaining hybrid nanostructures endowed by high regenerating and nourishing power. Nanostructures contain active nanocrystal easy to disperse thank to the collagen component that greatly intensify its activity and resorption properties. Moreover, this hydroxyapatite can be functionalized with ialuronic acid to boost the moisturizing and regenerating power.
  • Super-paramagnetic apatite (FeHA) to enhance the cutaneous permeability. Nowadays, additives are needed to promote the absorption and permeability. Fe-doped hydroxyapatite endowed by super-paramagnetic properties in presence of static o alternated external magnetic fields can generate small static magnetic field or hyperthermia respectively, don’t toxic for the health. These effects, controllable and activated in an independent way, increase the permeability promoting the absorption of active principles.
  • Calcium phosphates as additive in toothpaste. Amorphous calcium phosphates or fluoride substituted apatite are used as additive in toothpaste to promote the remineralization of dentinal tubules and decrease the dental sensitivity. The ions contained in apatitic crystalline lattice are soluble in the oral environment and promote the formation of new apatitic crystal giving a continuous mineralization during the daily tooth care.

Equipments and processes

The synthesis of complex hybrid devices, difficult to obtain by conventional fabrication techniques, is carried out by morpho-synthesis procedures in which macromolecular matrices are used as templates for heterogeneous nucleation of mineral phases.

Technologies used to develop biomimetic hybrid powder

  • Biomineralization
  • Freeze drying
  • Cross-linking
  • Micronization
Multisubstituted apatites for skin care and dental care

Main collaborations

  • KALICHEM, Brescia
  • CURASEPT, Saronno
  • INTERCOS, Milano


Publications & Patents

  • Iafisco, M., Degli Esposti, L., Ramírez-Rodríguez, G. B., Carella, F., Gómez-Morales, J., Ionescu, A. C., Brambilla, E., Tampieri, T., and Delgado-López, J. M. (2018). Fluoride-doped amorphous calcium phosphate nanoparticles as a promising biomimetic material for dental remineralization. Scientific reports, 8(1), 1-9.
  • Adamiano, A., Sangiorgi, N., Sprio, S., Ruffini, A., Sandri, M., Sanson, A., Gras, P., Grossin, D., Francès, C., Chatzipanagis, K. and Bilton, M. Biomineralization of a titanium-modified hydroxyapatite semiconductor on conductive wool fibers. Journal of Materials Chemistry B, 5(36) (2017) 7608-7621.
  • Iannotti, V., Adamiano, A., Ausanio, G., Lanotte, L., Aquilanti, G., Coey, J.M.D., Lantieri, M., Spina, G., Fittipaldi, M., Margaris, G. and Trohidou, K.,. Fe-Doping-Induced Magnetism in Nano-Hydroxyapatites. Inorganic Chemistry, 56(8) (2017), pp.4446-4458.
  • Tampieri A., D’Alessandro T., Sandri M., Sprio S., Landi E., Bertinetti L., Panseri S., Pepponi G., Goettlicher J., Bañobre-López M. and Rivas J. Intrinsic magnetism and hyperthermia in bioactive Fe-doped hydroxyapatite. In: Acta Biomaterialia 8(2) (2012) 843-51.
  • L. Bertinetti, C. Drouet, C. Combes, C. Rey, A. Tampieri, S. Coluccia, G. Martra Surface Characteristics of Nanocrystalline Apatites: Effect of Mg Surface Enrichment on Morphology, Surface Hydration Species, and Cationic Environments Langmuir 25(10) (2009) 5647–5654.
  • S. Sprio, A. Tampieri, E. Landi, M. Sandri, G. Logroscino et al. Physico-chemical properties and solubility behaviour of multi-substituted hydroxyapatite powders containing silicon. Mater Sci Eng C 28 (2008) pp. 179-187.
  • Landi E, Sprio S, Sandri M, Celotti G, Tampieri A. Development of Sr and CO3 co-substituted hydroxyapatites for biomedical applications. Acta Biomater 4 (2008) pp.656-63.
  • Sprio S, Sandri M, Landi E, Tampieri A. Synthesis and characterization of multi-substituted apatites and bio-hybrid composites containing silicon. J Appl Biom Biomech 5 (2007) 220.
  • E. Landi, A. Tampieri, M. Mattioli-Belmonte, G. Celotti, M. Sandri, A. Gigante, P. Fava, G. Biagini. Biomimetic Mg- and Mg,CO3- substituted Hydroxyapatites: Synthesis, Characterization and in Vitro Behaviour. J. Eur.Cer. Soc. 26 (2006) (13) pp. 2593-2601.
  • A. Tampieri, M. Sandri, E. Landi, G. Celotti, N. Roveri, M. Mattioli Belmonte, L. Virgili, F. Gabbanelli, G. Bigini. HA/alginate hybrid composites prepared through bio-inspired nucleation Acta Biomaterialia 1 (2005) pp. 343-351
  • Brevetto Internazionale (PCT/IB2017/051290) WO/2017/153888, 102016000023614: PHYSICAL SOLAR FILTER CONSISTING OF SUBSTITUTED HYDROXYAPATITE IN AN ORGANIC MATRIX Inventors: Sandri Monica, Sprio Simone, Tampieri Anna
  • Brevetto Internazionale (PCT/IB2011/053362) WO2012014172: Intrinsically Magnetic Hydroxyapatite. Tampieri A., Landi E., Sandri M., Pressato D., Rivas Rey J., Banobre M., Marcacci M.
  • Brevetto Internazionale (PCT/IB2006/002844) WO2007045954: A plurisubstituted hydroxyapatite and the composite thereof with a natural and/or synthetic polymer, their preparation and uses thereof. Landi E., Tampieri A., Celotti G., Sprio S., Pressato D., De Luca C.
  • Brevetto Internazionale (PCT/EP2005/050815) WO2005/082780 A1 Biomimetic compounds containing hydroxyapatites substituted with magnesium and carbonate, and the processes used to obtain them. Roveri. N., Biagini G., Tampieri A., Tosetti A., Altamura M., Goso C
  • ITRM20000604 (17/05/2002) Processo sol-gel di produzione di polveri di idrossiapatite. Bezzi G., Tampieri A. La Torretta T.M.G., Celotti G.