Abstract
BackgroundSuperparamagnetic nanoparticles (MNPs) have been progressively explored for their potential in biomedical applications and in particular as a contrast agent for diagnostic imaging, for magnetic drug delivery and more recently for tissue engineering applications. Considering the importance of having safe MNPs for such applications, and the essential role of iron in bone remodelling, this study developed and analysed novel biocompatible and bioreabsorbable superparamagnetic nanoparticles, that avoid the use of poorly tolerated magnetite based nanoparticles, for bone tissue engineering applications.ResultsMNPs were obtained by doping hydroxyapatite (HA) with Fe ions, by directly substituting Fe2+ and Fe3+ into the HA structure yielding superparamagnetic bioactive phase. In the current study, we have investigated the effects of increasing concentrations (2000 μg/ml; 1000 μg/ml; 500 μg/ml; 200 μg/ml) of FeHA MNPs in vitro using Saos-2 human osteoblast-like cells cultured for 1, 3 and 7 days with and without the exposure to a static magnetic field of 320 mT. Results demonstrated not only a comparable osteoblast viability and morphology, but increased in cell proliferation, when compared to a commercially available Ha nanoparticles, even with the highest dose used. Furthermore, FeHA MNPs exposure to the static magnetic field resulted in a significant increase in cell proliferation throughout the experimental period, and higher osteoblast activity.In vivo preliminary results demonstrated good biocompatibility of FeHA superparamagnetic material four weeks after implantation into a critical size lesion of the rabbit condyle.ConclusionsThe results of the current study suggest that these novel FeHA MNPs may be particularly relevant for strategies of bone tissue regeneration and open new perspectives for the application of a static magnetic field in a clinical setting of bone replacement, either for diagnostic imaging or magnetic drug delivery.
Highlights
Superparamagnetic nanoparticles (MNPs) have been progressively explored for their potential in biomedical applications and in particular as a contrast agent for diagnostic imaging, for magnetic drug delivery and more recently for tissue engineering applications
Considering the importance of having non-toxic MNPs for the above-mentioned applications, and the important role of iron in bone regeneration and remodelling, this study aimed to analyse for the first time novel superparamagnetic bioactive and bioresorbable nanoparticles obtained by doping hydroxyapatite (HA) with Fe ions in ideal condition aimed at limiting the formation of poorly tolerated magnetic secondary phase (i.e. Fe3O4)
Following this synthesis method, during the stage of HA formation, the crystallographic position Ca(1) and Ca(2) of the apatite lattice are selectively substituted by iron species, Fe3+ and Fe2+ respectively [26] generating two distinct interacting structural domains whose interaction provide an intrinsic superparamagnetism [22]
Summary
Superparamagnetic nanoparticles (MNPs) have been progressively explored for their potential in biomedical applications and in particular as a contrast agent for diagnostic imaging, for magnetic drug delivery and more recently for tissue engineering applications. We have investigated the effects of increasing concentrations (2000 μg/ml; 1000 μg/ml; 500 μg/ml; 200 μg/ml) of FeHA MNPs in vitro using Saos-2 human osteoblast-like cells cultured for 1, 3 and 7 days with and without the exposure to a static magnetic field of 320 mT. There are multiple criteria to design materials for bone regeneration, which include: osteoinductivity (capable of promoting the differentiation of progenitor cells down an osteoblastic lineage), osteoconductivity (support bone growth and encourage the ingrowth of surrounding bone), and osteointegration (integrative to the surrounding bone), biocompatibility (induce minimal toxic or immune response), safe and effective resorbability, similar mechanical properties to bone (so as to perform its load-bearing function), ability to shape to a wide range of defect geometries, and must meet all regulatory requirements for clinical use [1,2]. Decreasing the material size into the nanoscale, the surface area, the surface roughness and the surface area to volume ratios are dramatically increased leading to superior materials physiochemical properties and mimicking the hierarchical nanostructure of native tissue [5,6]
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