Zhen Geng

Strontium incorporation to optimize the antibacterial and biological characteristics of silver-substituted hydroxyapatite coating

Infection in primary total joint prostheses is attracting considerable attention. In this study, silver (Ag) was incorporated into hydroxyapatite (HA) using a hydrothermal method in order to improve its antimicrobial properties. Strontium (Sr) was added as a second binary element to improve the biocompatibility. The substituted HA samples were fixed on titanium (Ti) substrates by dopamine-assisted immobilization in order to evaluate their antibacterial and biological properties. The results showed that Ag and Sr were successfully incorporated into HA without affecting their crystallinity. Further, the antibacterial tests showed that all the Ag-substituted samples had good anti-bacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Despite their good antibacterial ability, the Ag-substituted samples showed evidence of cytotoxicity on MG63 cells, characterized by low cell density and poor spreadability. The addition of Sr to the Ag-substituted samples considerably reduced the cytotoxicity of Ag. Although the viability of the cells grown on the surfaces of co-substituted HA was not as high as that of the cells grown on the HA surfaces, it is believed that excellent antibacterial properties and good biological activity can be achieved by balancing the dosage of Sr and Ag.

Synthesis, characterization and the formation mechanism of magnesium- and strontium-substituted hydroxyapatite

Magnesium (Mg) and strontium (Sr) have been widely used in the field of implanted devices because of their excellent bioactivity. However, the local high ion concentration caused by the implant affects the growth of hydroxyapatite (Ca10(PO4)6(OH)2, HA), which is the main inorganic component of bone and teeth. Many studies have investigated the effect of Mg2+ and Sr2+ on the growth of HA, but no systematic research has been conducted to compare these two ions in terms of the growth of HA. In this study, the substitution of a series of Sr- and Mg-substituted HA was conducted through a conventional hydrothermal method. Comprehensive characterization techniques, including X-ray diffraction, inductive coupled plasma, field emission scanning electron microscopy, transmission electron microscopy, selected-area electron diffraction, thermo gravimetric-differential scanning calorimetry, and Fourier transform infrared spectroscopy, were used to examine the effects of Sr2+ and Mg2+ on the phase, morphology, crystallinity, chemical composition, thermal stability, and lattice parameters of HA. The results indicated that Mg ions partially substituted for calcium (Ca) ions in the apatite structure, thus decreasing the lattice parameters, partially adsorbing on the apatite surface that formed the amorphous phase, and inhibiting the crystal growth. By contrast, Sr ions fully substituted for Ca ions and increased the lattice parameters. Both Mg and Sr ions affected the morphology of HA. Crystallinity decreased with the addition of Mg ions (transition from the crystal to amorphous phase was between 30% and 40% Mg), but it was not affected by Sr ions. Thermostability decreased with the addition of Mg (a total weight loss from 8.06 wt% for 10% Mg to 25.81 wt% for 50% Mg), but it had no significant changes in the Sr-substituted samples.

Incorporation of silver and strontium in hydroxyapatite coating on titanium surface for enhanced antibacterial and biological properties

Implant-related infection in primary total joint prostheses has attracted considerable research attention. As a measure to improve the antimicrobial properties of implant materials, silver (Ag) was incorporated into calcium phosphate (CaP) coatings on Titanium (Ti) via a hydrothermal method. Further, strontium (Sr) was added as a binary dopant to reduce the cytotoxicity of Ag in the coatings. Results showed that the CaP coatings were uniformly deposited on Ti with enhanced hydrophilicity and nanoscale surface roughness. Moreover, cell adhesion, proliferation, and differentiation were improved after the CaP coating deposition. The antibacterial properties of the coatings were distinctly improved by the incorporation of Ag, but the cell proliferation and differentiation were significantly decreased. Owing to the incorporation of Sr, the Ag-CaP coatings were able to effectively counteract the negative effects of Ag while maintaining good antibacterial properties. In summary, hydrothermally deposited CaP coatings doped with Ag and Sr exhibit excellent biocompatibility and antimicrobial activity. Thus, such co-doped CaP coatings have considerable potential for orthopaedic implant modification.

Controlled release behaviour and antibacterial effects of antibiotic-loaded titania nanotubes.

Bacterial infections have been identified as the main cause of orthopaedic implant failure. Owing to their high antibiotic delivery efficiency, titania nanotubes loaded with antibiotics constitute one of the most promising strategies for suppressing bacterial infections. However, it is difficult to control the drug-release behaviour of such nanotubes. Although sealing the nanotubes with a polymer solution provides sustained release effects to a certain extent, it inevitably influences their initial antibacterial activity. This study reports on the controlled release of gentamicin sulphate (GS) from titania nanotube surfaces whereby their initial antibacterial activity remains unaffected. Titania nanotubes were fabricated via electrochemical anodization and loaded with GS through physical adsorption. Experimental results showed that this loading method is feasible and efficient. The GS-loaded titania nanotubes were further covered by a thin film comprising a mixture of GS and chitosan (GSCH). The release kinetics confirmed that the drug release could be controlled by this thin film. Moreover, such a film was shown to not only inhibit initial bacterial adherence owing to its strong antibacterial properties but also enhance cell viability. Thus, GS-loaded titania nanotubes coated with GSCH have considerable potential as biomaterials for preventing initial release and peri-implant infection in the field of orthopaedics.

Synthesis, characterization and biological evaluation of strontium/magnesium-co-substituted hydroxyapatite

The present study aims to investigate the contribution of two biologically important cations, Mg2+ and Sr2+, when co-substituted into the structure of hydroxyapatite (Ca10(PO4)6(OH)2, HA). The substituted samples were synthesized by a hydrothermal method that involved the addition of Mg2+ and Sr2+ containing precursors to partially replace Ca2+ in the apatite structure. Four co-substituted HA samples with different concentrations of Mg2+ and Sr2+ ((Mg + Sr)/(Mg + Sr + Ca) = 30%) were investigated, and they were compared with pure HA. Experimental results showed that only a limited amount of Mg (Mg/(Mg + Ca + Sr) < 14%) could successfully substitute for Ca in HA. In addition, Mg substitution resulted in reduced crystallinity, thermal stability and lattice parameters of HA. In contrast, Sr could fully substitute for Ca. Furthermore, the addition of Sr increased the lattice parameters of HA. Here, we obtained the cation leach liquor by immersing the prepared samples in a culture medium for cell experiments. The in vitro study showed that 10Mg20Sr promoted better MG63 cell attachment, proliferation and differentiation than HA. Thus, the presence of an appropriate proportion of Mg and Sr could play a significant role in the increased biocompatibility of HA.

Synthesis, Characterization, and Biological Evaluation of Nanostructured Hydroxyapatite with Different Dimensions

Nanosized hydroxyapatite (HA) is a promising candidate for a substitute for apatite in bone in biomedical applications. Furthermore, due to its excellent bone bioactivity, nanosized strontium-substituted HA (SrHA) has aroused intensive interest. However, the size effects of these nanoparticles on cellular bioactivity should be considered. In this study, nanosized HA and SrHA with different dimensions and crystallization were synthesized by hydrothermal methods. The phase, crystallization and chemical composition were analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), respectively. The morphology was observed under field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The degradation behaviors of the samples were monitored by determining the ions release profile with inductively coupled plasma mass spectrometry (ICP-MS). The releasing behavior of Ca2+ and Sr2+ showed that the degradation rate was proportional to the specific surface area and inversely proportional to crystallization. The in vitro experiment evaluated by MG63 cells showed that SrHA nanorods with a length greater than 100 nm had the best biological performance both in cell proliferation and differentiation (* p < 0.05 compared with HA-1 and SrHA-1; * p < 0.01 compared with HA-2). In addition, HA nanoparticles with a lower aspect ratio had better bioactivity than higher ones (* p < 0.05). This study demonstrated that nanosized HA and SrHA with subtle differences (including dimensions, crystallization, specific surface area, and degradation rate) could affect the cellular growth and thus might have an impact on bone growth in vivo. This work provides a view of the role of nano-HAs as ideal biocompatible materials in future clinical applications.

Nanosized strontium substituted hydroxyapatite prepared from egg shell for enhanced biological properties

The fabrication and application of bioactive hydroxyapatite has always been a research hot spot in the fields of orthopaedics. Now it is common to use calcium (Ca) salt as Ca2+ source to synthesise hydroxyapatite. And egg shell could be another promising raw material as Ca2+ source, which is not only economical but also biogenic. In this study, egg shell (ES)-hydroxyapatite was prepared by using egg shells via hydrothermal method. Furthermore, ES-Sr hydroxyapatite was synthesized by incorporation of bioactive element strontium (Sr2+) into ES-hydroxyapatite. The in vitro experiment showed that compared with hydroxyapatite, ES-hydroxyapatite showed better biological performances, which could be attributed to the trace elements in egg shell, such as magnesium (Mg). And the incorporation of Sr2+ could further enhance the bioactivity. These results indicated that apatite with high biological activity, which had great application prospects in orthopedics, could be produced by egg shells and the incorporation of Sr2+.

Unraveling the osteogenesis of magnesium by the activity of osteoblasts in vitro

Magnesium (Mg) alloys, having a unique combination of strength and degradation, are being explored for various craniofacial and orthopedic applications. Nevertheless, the underlying mechanism of Mg2+ to stimulate bone formation needs further investigation. In this in vitro study, the degradation behavior of pure Mg and the effect of Mg2+ on the activity of osteoblasts were elucidated. From the corrosion test, it was determined that the degradation of pure Mg was able to create an alkaline microenvironment. It was further determined that Mg2+ promoted the proliferation and differentiation of osteoblasts. By western blotting analysis, it was noted that Mg2+ increased the phosphorylation of ERK (enhanced the c-fos level) and induced GSK3β phosphorylation (enhanced the β-catenin levels). These results demonstrated that the degradation of Mg was able to promote the proliferation and differentiation of osteoblasts, which may be related to the newly created alkaline microenvironment and the osteogenesis potential of released Mg2+ through the MAPK/ERK signaling pathway.

The synergistic effect of strontium-substituted hydroxyapatite and microRNA-21 on improving bone remodeling and osseointegration

Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. As the population ages, improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Herein, we fabricated a titanium (Ti)-based SrHA/miR-21 composite coating that was generated by hydrothermal deposition of SrHA followed by miR-21 nanocapsule immobilisation. Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of Ti. In vitro experiments revealed that the composite coating was beneficial for osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of the angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength. Therefore, this method provides a new strategy for bone repair.

The Incorporation of Strontium in a Sodium Alginate Coating on Titanium Surfaces for Improved Biological Properties

Orthopedic implant failure is mainly attributed to the poor bonding of the implant to bone tissue. An effective approach to minimize the implant failure would be modifying the surface of the implant. Strontium (Sr) can stimulate the proliferation and differentiation of osteoblasts and reduce the activity of osteoclasts. In this study, a titanium (Ti) surface was successively functionalized by covalently grafting dopamine, sodium alginate (SA), and Sr2+ via the electrostatic immobilization method. The as-prepared coatings on the Ti surface were characterized by using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), and contact angle. The results indicated that the Sr-incorporated coatings were successfully prepared and that Sr distributed uniformly on the surface. A long-lasting and sustained Sr release had been observed in Sr2+ release studies. The Ti/DOPA/SA/Sr exhibited little cytotoxicity and a robust effect of Sr incorporation on the adhesion and spreading of MG63 cells. The proliferation and alkaline phosphatase (ALP) activity of MG63 cells were enhanced by immobilizing Sr2+ on the SA-grafted Ti. The Sr-containing coatings, which displayed excellent biocompatibility and osteogenic activity, may provide a promising solution for promoting the tissue integration of implants.