Enhancement of the Biological and Mechanical Performances of Sintered Hydroxyapatite by Multiple Ions Doping

Abstract

In the present work, hydroxyapatite (HA) nanoparticles doped with Mg 2+ , Sr 2+ , and Zn 2+ ions are developed by wet neutralization method and then sintered at 1,250 • C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of doping ions in the HA structure induced the formation of βTCP as secondary phase, during the sintering process, and we found that this effect is depending on the stability of the various doping ions in the hydroxyapatite lattice itself. We also found that the formation of βTCP as secondary phase, in turn, confines the grain growth of HA induced by the high-temperature sintering process, thus leading to a strong increase of the flexural strength of the bulk materials, according to Hall-Petchlike law. Furthermore, we found that the doping ions enter also in the structure of the βTCP phase; besides the grain growth confinement, also the solubility and ion release ability of the final materials were enhanced. In addition to ameliorate the mechanical performance, the described phenomena also activate multiple biofunctionalities: (i) ability to upregulate various genes involved in the osteogenesis, as obtained by human adipose stem cells culture and evaluated by array technology; (ii) enhanced resistance to the adhesion and proliferation of Gram+ and Gram-bacterial strains. Hence, our results open a perspective for the use of sintered multiple ion-doped HA to develop ceramic biodevices, such as plates, screws, or other osteosynthesis media, with enhanced strength, osteointegrability, and the ability to prevent post-surgical infections.

In Vitro Osteoinductivity Assay of Hydroxylapatite Scaffolds, Obtained with Biomorphic Transformation Processes, Assessed Using Human Adipose Stem Cell Cultures

“…S-HA at day 14 induced the up-regulation of ten genes including BMP2, COL2A1, SPP1 and SP7, which play important roles in the ossification process. In agreement, previous studies have reported that sintered hydroxylapatite induced the expression of osteogenic genes, including SPP1, in hASCs [19], while high proliferation and focal adhesion kinase activation were observed in human bone marrow mesenchymal stem cells (BM-MSCs) [20].…”

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

“…Biomaterials provide the biological structure that supports MSC osteogenic differentiation [2,[11][12][13][14][15][16][17][18]. The addition of ions has been proved to enhance the osteogenic potential of scaffolds [19]. Biological macromolecules, such as growth factors [20] and microRNAs (miRNAs) [21], as well as biophysical stimuli [22], can also be associated with scaffolds to increase cell differentiation.…”

Bone Regeneration and Oxidative Stress: An Updated Overview

“…Osteogenesis can also be influenced by external aspects such as mechanical forces and electromagnetic fields [ 96 , 97 ]. MSC osteogenic differentiation is supported by the utilized biomaterials [ 98 , 99 ], but the supplementation with ions enhances the osteogenic scaffold potential [ 100 ]. Cell differentiation can also be enhanced with the aid of microRNAs (miRNAs) [ 101 ], GFs [ 102 ], and biophysical stimuli [ 103 ].…”