Simultaneous co-substitution of Sr2+/Fe3+ in hydroxyapatite nanoparticles for potential biomedical applications
Introduction
The inorganic phase, calcium hydroxyapatite [HAp, Ca10 (PO4)6(OH)2] of hard tissues has been extensively used in reconstructive surgery, orthodontic and orthopedic substances, and three-dimensional printing of scaffolds owing to its excellent bioactive and osteoconductive features [1], [2], [3]. The large surface area of HAp blesses it to form strong bonding with neighboring bone and connective tissues in vivo. Currently, the synthetic HAp finds broad spectrum applications in wastewater purification, fuel cells, and gas sensors [4], [5], [6]. However, low mechanical strength of pristine HAp limits its potential for load bearing applications; while its use with stainless steel and titanium alloys is overshadowed by stress-corrosion and post-implant infections which result in post-implantation failure [5]. Such discrepancies can be overcome by growing HAp with the co-substituted chemical species present in the natural tissues. One such effective and viable approach for modifying the synthetic HAp is to feed it with the cationic or anionic substitutions such as CO32-,Cl-, F-, Fe3+,Sr2+, Ag+ into its lattice [7], [8].
Recently, the Fe/HAp has been explored as magnetic material for targeted drug delivery and heat mediator to treat bone cancer [9]. However, the role of iron in bone accumulation has only received slight attention. For example, Ereiba et al. reported the enhanced apatite forming ability and improved solubility of HAp upon iron incorporation into its structure [10]. The bone strength mainly relies on calcium (Ca) and vitamins (K and D) contents which can be further enhanced by the addition of trace elements, such as manganese (Mn), zinc (Zn), fluorine (F), copper (Cu), magnesium (Mg), strontium (Sr), boron (B) and iron (Fe) [11], [12], [13], [14]. The deficiency of these trace elements can reduce the bone mass which in turn enhances the risk of bone fracture. To this end, the addition of moderate concentration of bone trace element such as Sr into the HAp lattice can improve the osteoblast activity in addition to encouraging an antimicrobial retort to prevent bone infection such as osteomyelitis [11], [15].
Current investigations focus on the co-substitution of dual minerals into the HAp lattice for potential biomedical applications. The incorporation of dual mineral ions into the HAp lattice involves the replacement of Ca2+ ions to allow the substitution of new ions into the Ca sites. The HAp lattice possesses ten known Ca-sites with larger Ca(I) sites than Ca(II) where foreign ions can occupy these sites and affect its physico-chemical and biomechanical features [16], [17]. To this end, the co-substitution of Sr2+ and Fe3+ multifunctional bioactive elements into HAp lattice can serve as potential candidates to treat osteoporosis and osteosarcoma in addition to improve the bone strength [8], [18]. Additionally, pristine HAp is more stable mineral exhibiting good intrinsic bioactive features; thus incorporation of foreign ions such as Sr2+ and Fe3+ could result in the fabrication of more soluble material with enhanced bioactivity; thus the simultaneously Sr2+/Fe3+ co-substituted HAp nanoparticles can find potential bone transplant applications in vivo. Further, the release of Sr2+/Fe3+ ions can promote release of Ca2+ ions from Sr2+/Fe3+:HAp; thus it potentially activates the calcium channels which in turn inspire the cellular responses [5], [19].
The current study was aimed to simultaneously co-substitute Sr2+/Fe3+ in HAp nanoparticles and correlate their properties with pristine HAp. The HAp was prepared systematically through sonication-assisted aqueous precipitation method with an overall chemical doping concentration of Sr2+ and Fe3+ fixed at 10 mol% comparative to Ca2+ in the HAp lattice. To the best of authors’ knowledge, this is the first report of simultaneous enrichment of HAp with Sr2+/Fe3+ contents via sonication assisted technique. The multifunctional Sr2+/Fe3+ co-substituted HAp nanoparticles can find potential applications in bone tissue regeneration, targeted drug delivery, magnetic resonance imaging, and hyperthermia based cancer treatment.
Section snippets
Synthesis of pristine HAp and Sr2+/Fe3+co-substituted HAp nanoparticles
The Sr2+/Fe3+ co-substituted HAp nanoparticles were synthesized via aqueous precipitation method followed by the sonication technique using calcium nitrate tetrahydrate (Ca(NO3)2·4H2O), diammonium hydrogen phosphate ((NH4)2HPO4), strontium nitrate (Sr(NO3)2), ferric chloride hexahydrate (FeCl3·6H2O), and ammonium hydroxide (HN4OH) solution. Briefly, 1.0 M of Ca(NO3)2·4H2O solution was prepared in deionized distilled water with the desired concentrations of Sr(NO3)2·4H2O or FeCl3·6H2O as
Structural analyses of pristine HAp and Sr2+/Fe3+ co-substituted HAp nanoparticles
The Sr2+/Fe3+ co-substituted HAp samples evaluated by XRD showed single phase (solid solution) with hexagonal-like structure (space group, p63/m (176), JCPD = 24-0033) as illustrated in Fig. 1(A) ((a)–(f)). The synthesis process for simultaneously Sr2+/Fe3+ co-substituted HAp powder samples employed resulted in the synthesis of a small crystalline apatite with the crystallinity scope inferior to pristine HAp. The peak intensities of Sr10: HAp shifted slightly towards lower 2θ value indicating
Conclusions
Bioactive and biocompatible Sr2+/Fe3+ co-substituted HAp nanoparticles were synthesized by sonicated-assisted aqueous precipitation method. Physico-chemical properties confirmed that the synthesized HAp nanoparticles were single-phase containing all functional groups corresponding to the apatite structure. SEM micrographs indicated rod-like morphology of the nanoparticles and introduction of iron significantly reduced the average particle size. The ICP-OES and EDX analyses confirmed the
Acknowledgments
This research was funded by National Science Foundation of China (81672158). The authors would also like to acknowledge the Analytical and Testing Centre of Huazhong University of Science and Technology for different characterization analyses.
Conflicts of interest
The authors declare no conflicts of interest associated with publication of this manuscript.
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