Silicon-substituted Hydroxyapatite Research Articles

Thermal Stability of Iron- and Silicon-Substituted Hydroxyapatite Prepared by Mechanochemical Method

In this study, hydroxyapatite with the substitution of calcium cations by iron and phosphate by silicate groups was synthesized via a mechanochemical method. The as-prepared compounds have the general formula Ca10−xFex(PO4)6−x(SiO4)x(OH)2−xOx/2 with x = 0–1.5. The thermal stability of the as-prepared compounds was studied by ex situ annealing of powders in a furnace. It has been established that, at 800 °C for x ≤ 0.5, a partial decomposition of the substituted apatites occurs with the formation of the β–Ca3(PO4)2 phase. At high “x” values, the formation of this phase starts at the lower temperature of 700 °C, followed by the formation of Fe2O3 at 900 °C. The introduction of iron and silicate ions into the hydroxyapatite lattice was shown to decrease its thermal stability.

Effect of S53P4 bioactive glass content on structural and in-vitro behavior of hydroxyapatite/bioactive glass mixtures prepared by mechanical milling

This work presents silicon-substituted hydroxyapatite preparation through planetary ball milling using biogenic hydroxyapatite and different wt% of S53P4 bioactive glass (5, 10, 15, and 20 wt%) sources for the first time. The prepared mixtures showed a BHAp lattice contraction with SiO44− incorporation; rich- and poor-Si phases were subsequently identified. Furthermore, two types of interaction among the functional groups in the S53P4 and BHAp mixtures are proposed. First, the 95-5 (wt.%) sample displayed a BHAp lattice with SiO44−, CO32−, and OH− ions substitution. In samples with S53P4 BG content higher than 95-5, the lattice substitution was related to SiO44−, PO43−, and CO32− ions, and a dehydroxylation process occurred in the BHAp. Finally, the bioactive behavior of the samples was studied by immersion in Hank's solution for 7, 14, and 28 days. The results showed that the mixtures formed a bone-like apatite layer with a dune-like morphology that increased in size and quantity with increasing S53P4 content in the mixtures.

Influence of synthesis on the grain size distribution of Ca5GeP2O12

Modern implants are often based on silicon-doped hydroxyapatite for enhanced biological activity. Such materials still have drawbacks, such as high probability of bacterial infections on their surface during surgery. In this work, we obtained germanium-substituted calcium phosphates, which are isostructural to silicon-substituted hydroxyapatite and whitlockite. Additionally, they potentially possess antibacterial properties. We obtained Ge-substituted phosphate composition Ca5GeP2O12 by solid-state, sol-gel, and combustion synthesis. The samples were analyzed using powder X-ray diffraction. Solid-phase synthesis leads to the formation of whitlockite, whereas synthesis in solution leads to the formation of hydroxyapatite. The calculation of the grain size distribution shows that the smallest particles are formed when combustion synthesis is used, and the largest particles are obtained during solid-phase synthesis. This is correlated with the expected influence of stirring and temperature factors on the reaction path.

Mechanical and Biological Properties of Magnesium- and Silicon-Substituted Hydroxyapatite Scaffolds.

Magnesium (Mg)- and silicon (Si)-substituted hydroxyapatite (HA) scaffolds were synthesized using the sponge replica method. The influence of Mg2+ and SiO44− ion substitution on the microstructural, mechanical and biological properties of HA scaffolds was evaluated. All synthesized scaffolds exhibited porosity >92%, with interconnected pores and pore sizes ranging between 200 and 800 μm. X-ray diffraction analysis showed that β-TCP was formed in the case of Mg substitution. X-ray fluorescence mapping showed a homogeneous distribution of Mg and Si ions in the respective scaffolds. Compared to the pure HA scaffold, a reduced grain size was observed in the Mg- and Si-substituted scaffolds, which greatly influenced the mechanical properties of the scaffolds. Mechanical tests revealed better performance in HA-Mg (0.44 ± 0.05 MPa), HA-Si (0.64 ± 0.02 MPa) and HA-MgSi (0.53 ± 0.01 MPa) samples compared to pure HA (0.2 ± 0.01 MPa). During biodegradability tests in Tris-HCl, slight weight loss and a substantial reduction in mechanical performances of the scaffolds were observed. Cell proliferation determined by the MTT assay using hBMSC showed that all scaffolds were biocompatible, and the HA-MgSi scaffold seemed the most effective for cell adhesion and proliferation. Furthermore, ALP activity and osteogenic marker expression analysis revealed the ability of HA-Si and HA-MgSi scaffolds to promote osteoblast differentiation.

Silicon-substituted hydroxyapatite reinforced 3D printed gelatin membrane for guided bone regeneration

Guided bone regeneration (GBR) warrants a bioactive membrane with biocompatibility, host tissue integration, and clinical moldability along with adequate mechanical and physical properties. Hydroxyapatite (HA) incorporated membranes have shown to promote the functional and osteogenic activity of stromal cells towards GBR. Also, many studies have demonstrated that the addition of trace elements such as Silicon-substituted HA (SiHA) accelerates and enhances bioactivity compared to HA. In this study, HA and SiHA were incorporated with gelatin (Gel) which is a biocompatible, low-cost, and cell-attractant, and widely used material for GBR. The three-dimensional printed construct provides for topography with interconnected pores that permit selective cell occlusion; a desirable property for GBR. The objective of the study was to develop, characterize, and study the osteogenic potential of Gel-SiHA membrane for GBR.

Effect of MgO addition on the sinterability, mechanical properties and biological cell activities of sintered silicon-substituted hydroxyapatite

The effect of 1 wt% magnesium oxide (MgO) as sintering additive on the sintering behaviour, microstructure, mechanical properties and cell activities of 0.4 and 1.6 wt% silicon-substituted hydroxyapatite (MgO-0.4Si-HA and MgO-1.6Si-HA) was investigated. The powders were synthesized by the wet-chemical neutralization method and the compacts were pressureless sintered in air between 1150 and 1250 °C for 2 h. The results showed that MgO-0.4Si-HA promoted the formation of the secondary phase of β-TCP when sintered at 1250 °C, whilst the stability of the hydroxyapatite phase was not disrupted for the MgO-1.6Si-HA. The presence of MgO was found to be beneficial in suppressing grain growth of Si-HA when sintered at 1250 °C; however, it did not promote densification at lower temperatures (1150 and 1200 °C). It was observed that despite the lower densification, Vickers hardness and compressive strength of the MgO-Si-HA were higher than those of the undoped Si-HA samples. The beneficial effect of MgO in enhancing the biocompatibility of Si-HA has been revealed. It was found that the MgO-doped samples dramatically enhanced the osteogenic differentiation of MC3T3-E1 cells as shown from the higher cell proliferation, alkaline phosphatase activity and bone-like nodule formation when compared to pristine HA.

Semi-supervised recommender system for bone implant ratio recommendation

Millions of people suffer from bone loss and diseases each year, which give rise to bone-related medical treatments. Multi-material coatings composed of Silicon Substituted Hydroxyapatite (Si-HA) and Silver Substituted Hydroxyapatite (Ag-HA) potentiated its usage as an ideal bone implant material with favourable biological response and antibacterial properties, respectively. Each patient has different conditions (e.g. bone ages, bone density, position, and infection status) and specific bone implant requirement, thus requiring specific designs of Si-HA and Ag-HA bone implant material ratios. In this paper, a recommender system which took advantage of Wide&Deep recommendation architecture and DenseNet architecture was provided and a semi-supervised training process was utilized to recommend appropriate bone implant material ratio (Si-HA:Ag-HA) for each patient to improve the bone disease treatment and recovery. The proposed recommendation system could achieve high accuracy ( $$92.2\%$$ ) and efficiency (using only $$10\%$$ of labeled data) on test dataset, which could be potentially utilized in future clinical usages and provide doctors with decision support to make better clinical decisions.

The effect of strontium and silicon substituted hydroxyapatite electrochemical coatings on bone ingrowth and osseointegration of selective laser sintered porous metal implants.

Additive manufactured, porous bone implants have the potential to improve osseointegration and reduce failure rates of orthopaedic devices. Substantially porous implants are increasingly used in a number of orthopaedic applications. HA plasma spraying–a line of sight process—cannot coat the inner surfaces of substantially porous structures, whereas electrochemical deposition of calcium phosphate can fully coat the inner surfaces of porous implants for improved bioactivity, but the osseous response of different types of hydroxyapatite (HA) coatings with ionic substitutions has not been evaluated for implants in the same in vivo model. In this study, laser sintered Ti6Al4V implants with pore sizes of Ø 700 μm and Ø 1500 μm were electrochemically coated with HA, silicon-substituted HA (SiHA), and strontium-substituted HA (SrHA), and implanted in ovine femoral condylar defects. Implants were retrieved after 6 weeks and histological and histomorphometric evaluation were compared to electrochemically coated implants with uncoated and HA plasma sprayed controls. The HA, SiHA and SrHA coatings had Ca:P, Ca:(P+Si) and (Ca+Sr):P ratios of 1.53, 1.14 and 1.32 respectively. Electrochemically coated implants significantly promoted bone attachment to the implant surfaces of the inner pores and displayed improved osseointegration compared to uncoated scaffolds for both pore sizes (p<0.001), whereas bone ingrowth was restricted to the surface for HA plasma coated or uncoated implants. Electrochemically coated HA implants achieved the highest osseointegration, followed by SrHA coated implants, and both coatings exhibited significantly more bone growth than plasma sprayed groups (p≤0.01 for all 4 cases). SiHA had significantly more osseointegration when compared against the uncoated control, but no significant difference compared with other coatings. There was no significant difference in ingrowth or osseointegration between pore sizes, and the bone-implant-contact was significantly higher in the electrochemical HA than in SiHA or SrHA. These results suggest that osseointegration is insensitive to pore size, whereas surface modification through the presence of an osteoconductive coating plays an important role in improving osseointegration, which may be critically important for extensively porous implants.

Silicon-incorporated nanohydroxyapatite-reinforced poly(ε-caprolactone) film to enhance osteogenesis for bone tissue engineering applications

Biomaterials composed of polymers and bioceramics have great prospects to repair large and complicated bone defects. Here, we developed a composite film consisting of poly(ε-caprolactone) (PCL) and silicon-substituted hydroxyapatite (Si-HA) nanoparticles to enhance the osteogenic effects of the scaffold for bone tissue engineering applications. The results showed that the Si-HA nanoparticles obtained an even distribution in the PCL matrix, resulting in a homogeneous composite film. Compared to HA-incorporated PCL film, the addition of silicon did not cause hydrophilic alterations to the film surface. With the seeding of mouse calvarial preosteoblasts (MC3T3-E1), the cells exhibited the good behaviors of adhesion and growth on the PCL/Si-HA film. Compared to the PCL/HA films, incorporation of Si-HA nanoparticles in PCL/Si-HA films showed the increased production of alkaline phosphatase (ALP) and calcium content by MC3T3-E1 cells. These results suggested the suitability of the PCL/Si-HA composite film to elicit cellular growth and functional differentiation with the potential for bone tissue engineering applications.

Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis. Statement of significanceFor the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.

Synthesis of silicon-substituted hydroxyapatite using hydrothermal process

An alternative route for preparing silicon-substituted hydroxyapatite powders Ca10(PO4)6−x(SiO4)x(OH)2−x (Si-HAp); using different content of SiO4 (0.588–0.48M) in the aqueous solution of Si precursor was investigated. Tetramethylammonium silicate (TMAS) was used as a silicon precursor. The experiments were carried out via conventional hydrothermal treatments at 150°C for 10h. The Si-HAp nanoparticles obtained were characterized by X-ray diffraction (XRD), Fourier transform IR spectroscopy (FTIR), inductively coupled plasma AES (ICPAES) and scanning electron microscopy (SEM) techniques. A drastically decrease of the diffraction was not observed by increasing the Si content in the structure of the hydrothermally Si-Hap particles produced. A detailed structural analysis conducted by Rietveld refinement indicated that the incorporation of Si occurred in hydroxyapatite (HAp) lattice by partially replacing phosphate (PO43−) groups with silicate (SiO44−) groups. Raman and X-ray photoelectron spectroscopy (XPS) analysis confirmed the substitution of PO43− by SiO44− in the Si-HAp structure. The crystallite size decreases by increasing the Si molar content in the hexagonal HAp structure. TEM observations revealed that the Si-HAp produced have a high crystallinity. A slight decrease of the particle size of the Si-HAp compared to pure HAp was observed (from 60–100nm to 40–70nm). The morphological analysis revealed that all the SiHAp powders prepared have the rod-like shape. Additionally, a slight decrease in both length and diameter of nanorods was observed by increasing the silicon content, the minimum size obtained for the powders containing the largest amount of Si (20Si-HAp) 25 and 70nm. The presence of Si in the structure of the Si-HAp favored densification of the compacts treated at high temperature 1200°C in comparison with pure HAp.

Silicon-Substituted Hydroxyapatite Particles and Response of Adipose Stem Cells In Vitro

Due to the similarity of synthetic hydroxyapatite (HA) to natural bone tissue, but, because of its low degradation rate, the current study focuses on silicon-substituted HA (Si-HA) synthesis, characterization, and biological evaluations. Si-HA was successfully prepared through sol-gel processing route and characterized using SEM, EDX, XRD, and FTIR. Si-HA particles were found to be non-cytotoxic following exposure to adipose stem cells (ADSCs). In fact, Si-HA particles showed a high level of matrix mineralization following prolonged and continuous exposure to ADSCs. It is suggested that the incorporation of Si in HA structure positively affects cellular behavior, associated with a higher degradation rate, and subsequently greater level of ionic product release from Si-HA particles. Hydroxyapatite (HA) has long been applied as bone substitutes but its low degradation rate limits its application. One approach is the incorporation of silicon (Si) within HA structure. This study confirms that Si-substituted HA enhance stem cell proliferation and promote osteogenic differentiation. Hence, Si-HA could be utilized in composites, scaffolds, and coatings for bone-related disorders.

Advanced protocol to functionalize CaP bioceramic surface with peptide sequences and effect on murine pre-osteoblast cells proliferation

To bring osteoinductive properties to calcium phosphate (CaP) bioceramics, a silicon-substituted hydroxyapatite was functionalized by integrin-adhesive cyclic-pentapeptides (c-(DfKRG)). A new two-step protocol was set up to immobilize peptides at low and controlled density on the ceramic surface and limit contamination by adsorbed molecules. To this aim, a spacer bearing c-(DfKRG)-S-PEG6-NHS molecule was synthesized and bonded to an organosilane previously covalently bonded to the ceramic surface. The functionalized ceramic was tested in vitro for MC3T3-E1 murine pre-osteoblasts. CaP ceramic surface retained good biological properties thanks to low density of bonded molecules preserving part of the bioactive CaP surface free of bioorganic molecules. The final SiHA-T-PEG6-S-c-(DfKRG) was shown to increase cell density and to improve proliferation. Furthermore, the use of a strong and stable covalent bond between inorganic and organic parts prevented early burst release of the peptide and increased the persistence of its bioactivity over time. So, this CaP ceramic associating c-(DfKRG) by covalent grafting could be considered as promising new biomaterials for bone tissue engineering.

Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment

The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. Statement of SignificanceReconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.

Biomimetic Coating of a Titanium Substrate with Silicon-Substituted Hydroxyapatite

Silicon-substituted hydroxyapatite (Si-HA) materials have been synthesized from a model SBF solution with different concentrations of silicon ions. All of the samples prepared from an extracellular fluid solution at different concentrations of silicate ions have been shown to be single-phase and consist of hydroxyapatite. The nature of the silicon-containing reagent (Na2SiO3 or tetraethyl orthosilicate) has no effect on the structure of hydroxyapatite. Analysis of silicon-modified phosphate coatings on titanium substrates indicates that more complete Si-HA deposition occurs on etched samples during the first three days of holding in the model solution. After exposure of Si-HA-coated titanium substrates to a high-power ion beam, further crystal growth and surface regeneration are possible.

Surface modification of zirconia substrate by silicon-substituted hydroxyapatite coating for enhanced bioactivity

Surface modification of zirconia substrate by silicon-substituted hydroxyapatite coating for enhanced bioactivity

Characterization and biological properties of a novel synthesized silicon-substituted hydroxyapatite derived from eggshell.

In the present study, the effect of adding different concentrations of silicon on physical, mechanical and biological properties of a synthesized aqueous precipitated eggshell-derived hydroxyapatite (e-HA) was evaluated. No secondary phases were detected by X-ray diffraction for the specimens e-HA and e-HA containing silicon (Si-e-HAs) before and after heating at 1200°C. A reduction in the crystallite size and a-axis as well as an increase in c-axis was occurred when silicon replacement was happened in the structure of e-HA. The presence of Si-O vibrations and carbonate modes for Si-e-HAs was confirmed by Fourier transform infrared spectroscopy analysis. The range of porosity and density was varied from 25% and 2.4 g cm-3 to 7% and 2.8 g cm-3 for e-HA and Si-e-HAs. The values of Young's modulus ( E) and compressive strength were varied for e-HA and Si-e-HAs. The porous structure of the samples was reduced when they were heated as e-HA kept the porous microstructure containing some dense areas and Si-e-HAs possessed a rough surface including slight levels of microporosity. The acellular in vitro bioactivity represented different apatite morphologies for e-HA and Si-e-HAs. The G-292 osteoblastic cells were stretched well on the surface with polygon-shaped morphology for 0.8Si-e-HA after 7 days of culture. According to MTT assay and alkaline phosphatase test, the maximum cell activity was related to 0.8Si-e-HA. The minimum inhibitory concentration for 0.8Si-e-HA and e-HA was estimated to be about 3.2 and 4.4 mg/mL, respectively. In overall, the sample 0.8Si-e-HA exhibited a higher bacteriostatic effect than e-HA against gram-negative bacterial strain Escherichia coli.

A comparative study on the in-vitro antibacterial behaviour of chemically-modified calcium phosphate coatings

ABSTRACT Drop-on-demand (DoD) micro dispensing technique, which enabled nano apatite crystals including hydroxyapatite (HA), silicon-substituted HA (SiHA), silver-substituted HA (AgHA) droplets to be deposited on glass substrate with precise placement, size, and number of droplets was presented in this work. Multi-material coatings containing SiHA:AgHA = 1:3 (1SiHA-3AgHA) were fabricated for obtaining favourable bioactivity and enhanced antibacterial properties. The antibacterial effect of 1SiHA-3AgHA towards Escherichia coli (E. coli) indicated a delayed exponential growth for up to 24 h, with significantly less bacteria adhesion compared to HA and SiHA coatings. The biological response of adipose-derived mesenchymal stem cells (hASCs) cultured on 1SiHA-3AgHA coatings exhibited enhanced cell attachment, proliferation and differentiation, as compared to HA and AgHA coatings. Hence, DoD micro deposition technique could be potentially used in producing multi-material coatings for biomedical applications.

Deposition of substituted apatite coatings at different coating patterns via drop-on-demand micro-dispensing technique

Silicon-substituted hydroxyapatite (SiHA) and silver-substituted hydroxyapatite (AgHA) potentiated their usages as bone graft materials with favourable bioactivity and enhanced antibacterial properties, respectively. To facilitate bone growth and reduce bacterial adhesion simultaneously, multi-material coatings composed of SiHA and AgHA at ratios of 1:1, 1:2, 1:3 (1SiHA-1AgHA, 1SiHA-2AgHA, 1SiHA-3AgHA), were deposited by different coating patterns via a Drop-on-Demand (DoD) micro-dispensing technique. As an additive manufacturing technique, placement, size, and numbers of droplets could be controlled precisely, and this gave rise to an even distribution of SiHA and AgHA, which integrated functional properties to a thin coating layer of 9·0 ± 0·5 μm. From the antibacterial study, SiHA-AgHA coatings, especially 1SiHA-3AgHA coatings demonstrated an inhibition on the growth of Escherichia coli (E. coli) up to 12 h as compared to pure HA and SiHA coatings.

Polyethylene Oxide and Silicon-Substituted Hydroxyapatite Composite: A Biomaterial for Hard Tissue Engineering in Orthopedic and Spine Surgery.

Background:Tissue engineering and biomaterials have made it possible to innovate bone treatments for orthopedic and spine problems. The aim of this study is to develop a novel polyethylene oxide (PEO)/silicon-substituted hydroxyapatite (Si-HA) composite to be used as a scaffold for hard tissue engineering in orthopedic and spine procedures.Materials and Methods:The composite was fabricated through the electrospinning technique. The applied voltage (5 kV) and PEO concentration (5%) were fixed. Processing parameters such as the flow rates (20 μl/min and 50 μl/min), distances from capillary tube to the collector (130 mm and 180 mm), spinning time (10 min and 20 min), and concentration of Si-HA (0.2% and 0.6%) were explored to find the optimum conditions to produce fine composite fibers.Results:Scanning electron microscope images showed that 5% PEO, 5% PEO/0.2% Si-HA, and 5% PEO/0.6% Si-HA fibers were successively produced. Flow rates and working distances showed significant influence on the morphology of the polymeric and composite fibers. A high flow rate (50 μl/min) and a larger working distance (180 mm) resulted in larger fibers. The comparison between the mean fiber diameter of 5% PEO/0.2% Si-HA and 5% PEO/0.6% Si-HA showed to be significantly different. As the Si-HA concentration increased, certain fibers were having particles of Si-HA that were not properly integrated into the polymer matrix.Conclusions:Synthesis of a novel biomaterial for hard tissue scaffold through electrospinning was successful. In general, PEO/Si-HA fibers produced have the desired characteristics to mimic the extracellular matrix of bone.