Advanced Mg, Zn, Sr, Si Multi-Substituted Hydroxyapatites for Bone Regeneration

Int J Nanomedicine. 2020 Feb 13;15:1037-1058. doi: 10.2147/IJN.S226630. eCollection 2020.


Purpose: Compositional tailoring is gaining more attention in the development of advanced biomimetic nanomaterials. In this study, we aimed to prepare advanced multi-substituted hydroxyapatites (ms-HAPs), which show similarity with the inorganic phase of bones and might have therapeutic potential for bone regeneration.

Materials: Novel nano hydroxyapatites substituted simultaneously with divalent cations: Mg2+ (1.5%), Zn2+ (0.2%), Sr2+ (5% and 10%), and Si (0.2%) as orthosilicate (SiO4 4-) were designed and successfully synthesized for the first time.

Methods: The ms-HAPs were obtained via a wet-chemistry precipitation route without the use of surfactants, which is a safe and ecologically friendly method. The composition of synthesized materials was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The materials were characterized by X-ray powder diffraction (XRD), FT-IR and FT-Raman spectroscopy, BET measurements and by imaging techniques using high-resolution TEM (HR-TEM), FE-SEM coupled with EDX, and atomic force microscopy (AFM). The ion release was measured in water and in simulated body fluid (SBF).

Results: Characterization methods confirmed the presence of the unique phase of pure stoichiometric HAP structure and high compositional purity of all synthesized nanomaterials. The doping elements influenced the crystallite size, the crystallinity, lattice parameters, morphology, particle size and shape, specific surface area, and porosity. Results showed a decrease in both nanoparticle size and crystallinity degree, coupled with an increase in specific surface area of these advanced ms-HAP materials, in comparison with pure stoichiometric HAP. The release of biologically important ions was confirmed in different liquid media, both in static and simulated dynamic conditions.

Conclusion: The incorporation of the four substituting elements into the HAP structure is demonstrated. Synthesized nanostructured ms-HAP materials might inherit the in vivo effects of substituting functional elements and properties of hydroxyapatite for bone healing and regeneration. Results revealed a rational tailoring approach for the design of a next generation of bioactive ms-HAPs as promising candidates for bone regeneration.

Keywords: bioceramics; characterization; hydroxyapatite; ions release; multi-substituted hydroxyapatites; nanomaterials; synthesis.

MeSH terms

  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Bone Regeneration / physiology*
  • Hydroxyapatites / chemistry*
  • Metals / chemistry*
  • Metals / pharmacokinetics
  • Nanostructures / chemistry*
  • Particle Size
  • Porosity
  • Spectroscopy, Fourier Transform Infrared / methods
  • Spectrum Analysis, Raman / methods
  • X-Ray Diffraction


  • Hydroxyapatites
  • Metals