Abstract
In the present work, hydroxyapatite nanoparticles (HA) doped with Mg2+, Sr2+ and Zn2+ ions are developed by wet neutralization method and then sintered at 1250 °C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of ion doping in the HA structure induced the formation of betaTCP as secondary phase, during the sintering process, and we found that this effect is depending on the solubility and stability of the various doping ions in the hydroxyapatite lattice itself. We also found that the formation of betaTCP 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-Petch-like law. Furthermore, we found that the doping ions enter also in the structure of the betaTCP 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 bio-functionalities: i) ability to up-regulate 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 bio-devices such as plates, screws or other osteosynthesis media, with enhanced strength, osteointegrability and ability to prevent post-surgical infections.
Highlights
Since decades, extensive research is being engaged for the development of synthetic biodevices with improved biological and mechanical functionality, suitable for application in bone surgery (Munch et al, 2008; Dutta et al, 2015)
While several investigations of the effects of doping ions have been carried out on nanocrystalline and nanostructured HAs obtained by low temperature wet synthesis, there are very few studies investigating the biological effect of these ions in sintered ceramics, but they are limited to calcium silicate phases (Wu et al, 2007; Zreiqat et al, 2010; Liu et al, 2019)
The results obtained in the present work show that when HA powders obtained by wet synthesis process are sintered, the doping of the apatitic crystals with multiple ions is able to induce the formation of HA/βTCP composites with enhanced mechanical and biologic ability
Summary
Extensive research is being engaged for the development of synthetic biodevices with improved biological and mechanical functionality, suitable for application in bone surgery (Munch et al, 2008; Dutta et al, 2015). The occurrence of postsurgical infections is a major concern, due to the antibiotic resistance of various bacterial strains, a phenomenon that is constantly growing and that will become, more and more, a primary cause of failure of surgical interventions, in orthopedics (Li and Webster, 2018; Hofer, 2019) To overcome these drawbacks, a growing literature is investigating the possibility of developing biomaterials capable to establish tight bone-implant interfaces thanks to improved mechanical properties and to superior osteointegrative and anti-infective ability. Recent studies report that the multiple doping of HA with these ions can promote inherent antiinfective properties (Ballardini et al, 2018; Sprio et al, 2019), being promising for the development of new medical devices with enhanced bioactivity and osteointegrability while preventing adverse infective complications, at the same time. In spite of the urging need of implantable biodevices capable of counteracting the formation of biofilms, studies on the antibacterial ability of ion-doped sintered CaPs have not yet been reported
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