The influences of poly(lactic-co-glycolic acid) (PLGA) coating on the biodegradability, bioactivity, and biocompatibility of calcium silicate bioceramics

Calcium silicate (CaSiO₃) bioceramics and polyesters have complementary qualities as potential bone substituted materials. In this study, sintered CaSiO₃ bioceramics were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the influences of the PLGA coating on the degradation, hydrophilicity, bioactivity, and biocompatibility of CaSiO₃ ceramics were investigated. The results showed that the degradation rate was reduced, while hydrophilicity was decreased with the increase of the polymer coating. In addition, the polymer coating resulted in a decrease of the alkaline pH value during the degradation of the ceramics, which indicated an increase of the cell biocompatibility, confirmed by the attachment and proliferation of rMSCs on the surface of the polymer-coated ceramics. Furthermore, the apatite-forming ability of the PLGA-coated CaSiO₃ bioceramics was maintained. This study suggested that the coating with PLGA might be a useful method to improve the integrative properties of CaSiO₃ bioceramics for applications in bone regeneration and bone tissue engineering.     

Functional Materials for Bone Regeneration from Beta‐Tricalcium Phosphate

Biodegradable ceramics of β‐tricalcium phosphate (β‐TCP, Ca₃(PO₄)₂) are widely used as bone regeneration materials. The goal is a complete regeneration of the bony defect (restitutio ad integrum = full recovery). Different bioceramics made of β‐TCP show fundamental differences in terms of phase purity, primary particle size, stability, porosity, solubility and therefore biodegradation of the material. Cerasorb® is a bioceramic consisting of phase pure β‐TCP. The primary particle size in connection with a stable sinter structure forms a porous biomaterial which is optimised in the functional surface, porosity and resorption/degradation behaviour. Different forms of Cerasorb® are available: granular materials with high and low porosity optimised for specific indications as well as block forms shapeable by the surgeon for various bony defects.     

Polyfunctional bioceramics modified by M-type hexagonal ferrite particles for medical applications

Magnetic bioceramics based on Ca₅(PO₄)₃OH hydroxyapatite and M-type hexagonal ferrite (HF) microcrystals has been synthesized and characterized. The material consists of a biocompatible apatite matrix containing dispersed M-type HF particles. The latter component makes the magnetic characteristics of synthesized ceramics significantly higher as compared to those of iron-oxide-modified bioglass ceramics currently used in medicine. These properties increase the efficiency and prospects of using the new bioceramics in medicine, in particular, for the hyperthermal treatment of malignant tumors. Thus, a new class of materials is created, which combine the necessary biocompatibility and biological activity of Ca₅(PO₄)₃OH hydroxyapatite and high magnetic characteristics of M-type HF microcrystals.     

Biphasic calcium phosphate bioceramics: preparation, properties and applications

Biphasic calcium phosphate (BCP) bioceramics belong to a group of bone substitute biomaterials that consist of an intimate mixture of hydroxyapatite (HA), Ca₁₀(PO₄)₆(OH)₂, and beta-tricalcium phosphate (-TCP), Ca₃(PO₄)₂, of varying HA/-TCP ratios. BCP is obtained when a synthetic or biologic calcium-deficient apatite is sintered at temperatures at and above 700 °C. Calcium deficiency depends on the method of preparation (precipitation, hydrolysis or mechanical mixture) including reaction pH and temperature. The HA/-TCP ratio is determined by the calcium deficiency of the unsintered apatite (the higher the deficiency, the lower the ratio) and the sintering temperature. Properties of BCP bioceramics relating to their medical applications include: macroporosity, microporosity, compressive strength, bioreactivity (associated with formation of carbonate hydroxyapatite on ceramic surfaces in vitro and in vivo), dissolution, and osteoconductivity. Due to the preferential dissolution of the -TCP component, the bioreactivity is inversely proportional to the HA/-TCP ratio. Hence, the bioreactivity of BCP bioceramics can be controled by manipulating the composition (HA/-TCP ratio) and/or the crystallinity of the BCP. Currently, BCP bioceramics is recommended for use as an alternative or additive to autogeneous bone for orthopedic and dental applications. It is available in the form of particulates, blocks, customized designs for specific applications and as an injectible biomaterial in a polymer carrier. BCP ceramic can be used also as grit-blasting abrasive for grit-blasting to modify implant substrate surfaces. Exploratory studies demonstrate the potential uses of BCP ceramic as scaffold for tissue engineering, drug delivery system and carrier of growth factors.     

Synthetic silicate sulphate apatite: mechanical properties and biocompatibility testing

The solid solution series of Ca₁₀(PO₄)₆F₂–Ca₁₀(SiO₄)₃(SO₄)₃F₂ was synthesized by solidstate methods. Tensile strength testing by diametral compression indicated that the silicate sulphate apatites have strength comparable with that of phosphate apatite, with the centre member of the solid solution series [Ca₁₀(PO₄)₃(SiO₄)_1.5(SO₄)_1.5F₂] having the highest tensile strength of 20.7 MN m^–2. The in vivo behaviour of three compositions was evaluated. These materials have increased resorption rate compared with phosphate apatite, and good biocompatibility. The silicatian sulphatian apatites appear to be excellent materials for lowload-bearing bone graft applications.     

Bioceramics composition modulate resorption of human osteoclasts

Biomaterials used in bone regeneration are designed to be gradually resorbed by the osteoclast and replaced by new bone formed through osteoblastic activity. The aim of the present study is to analyze the role of osteoclasts in the resorption process. The attachment of human osteoclasts and the appearance of their resorption lacunae, when cultured on either the resorbable crystalline, calcium orthophosphate materials or on the long-term stable bioceramic material was investigated. The resorbable materials contain Ca₁₀[K,Na](PO₄)₇ (AW-Si) and Ca₂KNa(PO₄)₂ (GB14, GB9 & D9/25) as their main crystal phases, however they differ in their total solubility. These differences result from small variations in the composition. The long-term stable material consist of about 30% fluorapatite beside calcium zirconium phosphate (Ca₅(PO₄)3F + CaZr₄(PO₄)₆) and shows a very small solubility. AW-Si has an alkali containing crystalline phase, Ca₁₀[K,Na](PO₄). While GB14, GB9 and D9/25 contain the crystalline phase Ca₂KNa(PO₄)₂ with small additions of crystalline and amorphous diphosphates and/or magnesium potassium phosphate (GB14). D9/25 and AW-Si is less soluble compared to GB14, and GB9 among the resorbable materials. Resorbable and long-term stable materials vary in their chemical compositions, solubility, and surface morphology. Osteoclasts modified the surface in their attempts to resorb the materials irrespective of the differences in their physical and chemical properties. The depth and morphology of the resorption imprints were different depending on the type of material. These changes in the surface structure created by osteoclasts are likely to affect the way osteoblasts interact with the materials and how bone is subsequently formed.     

Recent advances in silicate-based crystalline bioceramics for orthopedic applications: a review

The present article critically reviewed the potentiality of Mg–Ca silicate-based crystalline bioceramics such as MgSiO₃, Mg₂SiO₄, CaSiO₃, Ca₂SiO₄, Ca₃SiO₅, CaMgSi₂O_6, Ca₂MgSi₂O₇, Ca₇MgSi₄O₁₆, CaMgSiO₄ and Ca₃MgSi₂O₈ as new generation orthopedic prosthetic implants. Mg²⁺, Ca²⁺ and Si⁴⁺ ions are abundant in bone and play a crucial role in various bone metabolic activities such as enhancing osteogenesis and inhibiting osteoporosis. The release rate of Mg²⁺, Ca²⁺ and Si⁴⁺ ions from these bioceramics depends on the crystal structure which consequently, influences their bioactivity and biocompatibility. In addition, the release rate of these ions can be tuned by tailoring the processing parameters/routes and compositional modifications and subsequently, bioactivity, cellular response as well as bone regeneration ability can be improved. Toward this end, the present article thoroughly reviewed and analyzed the influence of crystal structure, processing parameters/routes and compositional alteration on in vitro/in vivo biocompatibility and degradation behavior of the above ceramics. Further, a correlation between structure, processing and properties has been established.

     

Hydrothermal synthesis of Ca2(SiO3)(OH)2 microbelts and their transformation to β-Ca2SiO4 microbelts by microwave heating

Calcium silicates possess potential applications in biomedical fields such as drug delivery and bone tissue regeneration owing to their comparatively good bioactivity, biocompatibility and biodegradability. In this paper, we report the preparation of monoclinic β-Ca₂SiO₄ microbelts by microwave thermal transformation of Ca₂(SiO₃)(OH)₂ microbelts at 670 °C for 2 h. Ca₂(SiO₃)(OH)₂ microbelts are successfully used as both the precursor source material and the template for the preparation of β-Ca₂SiO₄ microbelts. The morphology and size of Ca₂(SiO₃)(OH)₂ microbelts can be well preserved during the microwave thermal transformation process. Ca₂(SiO₃)(OH)₂ microbelts are synthesized using Na₂SiO₃?9H₂O, NaOH and Ca(NO₃)₂?4H₂O in the solvent of water by a hydrothermal method at 200 °C for 24 h. The products are characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM).     

Resorption of Ca<Subscript>3 – <Emphasis Type="Italic">x</Emphasis></Subscript>M<Subscript>2<Emphasis Type="Italic">x</Emphasis></Subscript>(PO<Subscript>4</Subscript>)<Subscript>2</Subscript> (M = Na,K) Calcium Phosphate Bioceramics in Model Solutions

The resorbability of bioceramics in the Ca₃(PO₄)₂–CaNaPO₄–CaKPO₄ system is evaluated in an approach involving thermodynamic assessment of solubility and investigation of the dissolution kinetics in model media, in particular in citric acid solutions. Thermodynamic calculation indicates high solubility of the Ca₅Na₂(PO₄)₄, α-CaМPO₄, β-CaKPO₄, and β-СаK_0.6Na_0.4PO₄ phases. Investigation of the dissolution kinetics of ceramics has made it possible to identify two distinct types of behavior of resorbable materials in weakly acidic solutions: with fast resorption kinetics in the case of the phases based on nagelschmidtite solid solutions and α-CaМPO₄ disordered high-temperature solid solutions, and with a nearly constant, relatively low dissolution rate and a high solubility limit in the case of β-СaK_{1 – x}Na _x -based phases.     

Biomorphous porous hydroxyapatite-ceramics from rattan (<Emphasis Type="Italic">Calamus Rotang</Emphasis>)

The three-dimensional, highly oriented pore channel anatomy of native rattan (Calamus rotang) was used as a template to fabricate biomorphous hydroxyapatite (Ca₅(PO₄)₃OH) ceramics designed for bone regeneration scaffolds. A low viscous hydroxyapatite-sol was prepared from triethyl phosphite and calcium nitrate tetrahydrate and repeatedly vacuum infiltrated into the native template. The template was subsequently pyrolysed at 800°C to form a biocarbon replica of the native tissue. Heat treatment at 1,300°C in air atmosphere caused oxidation of the carbon skeleton and sintering of the hydroxyapatite. SEM analysis confirmed detailed replication of rattan anatomy. Porosity of the samples measured by mercury porosimetry showed a multimodal pore size distribution in the range of 300 nm to 300 μm. Phase composition was determined by XRD and FT-IR revealing hydroxyapatite as the dominant phase with minimum fractions of CaO and Ca₃(PO₄)₂. The biomorphous scaffolds with a total porosity of 70–80% obtained a compressive strength of 3–5 MPa in axial direction and 1–2 MPa in radial direction of the pore channel orientation. Bending strength was determined in a coaxial double ring test resulting in a maximum bending strength of ~2 MPa.     

Na-doped β-tricalcium phosphate: physico-chemical and in vitro biological properties

Synthetic calcium phosphate ceramics as β-tricalcium phosphate (Ca₃(PO₄)₂; β-TCP) are currently successfully used in human bone surgery. The aim of this work was to evaluate the influence of the presence of sodium ion in β-TCP on its mechanical and biological properties. Five Na-doped-β-TCP [Ca_10.5−x/2Na _x (PO₄)₇, 0 ≤ x ≤ 1] microporous pellets were prepared via solid phase synthesis, and their physico-chemical data (lattice compacity, density, porosity, compressive strength, infrared spectra) denote an increase of the mechanical properties and a decrease of the solubility when the sodium content is raised. On the other hand, the in vitro study of MC3T3-E1 cell activity (morphology, MTS assay and ALP activity) shows that the incorporation of sodium does not modify the bioactivity of the β-TCP. These results strongly suggest that Na-doped-β-TCP appear to be good candidates for their use as bone substitutes.     

Impartation of apatite‐forming ability to chitosan nanofibres by using apatite nuclei

Chitosan nanofibre–apatite nuclei composites obtained by mixing apatite nuclei which possess high apatite‐forming ability with chitosan nanofibre have been expected to be novel bone restorative materials with suitable properties such as light weight, low coefficient of thermal expansion, high mechanical strength, biocompatibility and bioactivity. In this study, the authors prepared three types of apatite nuclei by changing the reaction time aimed to optimise their crystallinity and fabricated their composites with chitosan nanofibre. In order to evaluate the bioactivity in vitro, the authors tested apatite‐forming ability in simulated body fluid. As a result, the materials showed enough apatite‐forming ability in a short time by mixing chitosan nanofibre and apatite nuclei with extremely low crystallinity and their high reactivity in simulated body fluid.Inspec keywords: calcium compounds, nanofibres, bioceramics, bone, polymer fibres, nanocomposites, filled polymers, nanomedicine, nanofabricationOther keywords: apatite‐forming ability, chitosan nanofibre‐apatite nuclei composites, bone restorative materials, reaction time, crystallinity, in vitro bioactivity, simulated body fluid, Ca₁₀ (PO₄)₆ (OH)₂      

Preparation of highly porous hydroxyapatite from cuttlefish bone

Hydroxyapatite structures for tissue engineering applications have been produced by hydrothermal (HT) treatment of aragonite in the form of cuttlefish bone at 200°C. Aragonite (CaCO₃) monoliths were completely transformed into hydroxyapatite after 48 h of HT treatment. The substitution of CO₃ ²⁻ groups predominantly into the PO₄ ³⁻ sites of the Ca₁₀(PO₄)₆(OH)₂ structure was suggested by FT-IR spectroscopy and Rietveld structure refinement. The intensity of the ν₃PO₄ ³⁻ bands increase, while the intensity of the ν₂CO₃ ²⁻ bands decrease with the duration of HT treatment resulting in the formation of carbonate incorporating hydroxyapatite. The SEM micrographs have shown that the interconnected hollow structure with pillars connecting parallel lamellae in cuttlefish bone is maintained after conversion. Specific surface area (S _BET) and total pore volume increased and mean pore size decreased by HT treatment.     

Electrophoretic deposition of hydroxyapatite‐shrimp crusts nanocomposite thin films for bone implant studies

Hydroxyapatite‐shrimp crusts nanocomposite thin films were deposited on titanium substrates by electrophoretic technique, under different preparation conditions, for bone implant applications. Fourier transform infrared spectrometer, atomic force microscope, X‐ray diffraction (XRD), optical microscope, and scanning electron microscope were employed to characterise the synthesised films. Vickers’ micro‐hardness measurements revealed a value of 502 HV for the hydroxyapatite films and 314.55 HV for the nanocomposite films. XRD results confirmed the polycrystalline nature of the hydroxyapatite and hydroxyapatite‐shrimp nanocomposite films. The in‐vitro bioactivity test of the synthesised films in simulated body fluid showed very low dissolution rate. Antibacterial activity of synthesised films was investigated against E. coli bacteria.Inspec keywords: electrophoretic coating techniques, thin films, nanocomposites, antibacterial activity, bone, prosthetics, nanomedicine, calcium compounds, bioceramics, nanofabrication, Fourier transform infrared spectra, atomic force microscopy, X‐ray diffraction, optical microscopy, scanning electron microscopy, Vickers hardness, microhardness, microorganisms, dissolvingOther keywords: Ti, Ca₁₀ (PO₄)₆ (OH)₂ , E. coli bacteria, antibacterial activity, dissolution rate, simulated body fluid, in‐vitro bioactivity test, polycrystalline nature, Vickers microhardness measurements, XRD, scanning electron microscopy, optical microscopy, X‐ray diffraction, atomic force microscopy, Fourier transform infrared spectrometer, bone implant applications, titanium substrates, hydroxyapatite‐shrimp crust nanocomposite thin films, electrophoretic deposition     

Bioactivity and mineralization of hydroxyapatite with bioglass as sintering aid and bioceramics with Na3Ca6(PO4)5 and Ca5(PO4)2SiO4 in a silicate matrix

Hydroxyapatite and Bioglass^®-45S5 were sintered together creating new ceramic compositions that yielded increased apatite deposition and osteoblast differentiation and proliferation in vitro compared to hydroxyapatite. The sintered products characterized by X-ray diffraction, revealed hydroxyapatite as the main phase when small quantities (1, 2.5 and 5 wt.%) of bioglass was added. Bioglass behaved as a sintering aid with β-TCP (Ca₃(PO₄)₂) being the minor phase. The amount of β-TCP increased with the amount of bioglass added. In compositions with larger additions of bioglass (10 and 25 wt.%), new phases with compositions of calcium phosphate silicate (Ca₅(PO₄)₂SiO₄) and sodium calcium phosphate (Na₃Ca₆(PO₄)₅) were formed respectively within amorphous silicate matrices. In vitro cell culture studies of the ceramic compositions were examined using bone marrow stromal cell (BMSC). Cell proliferation and differentiation of bone marrow stromal cells into osteoblasts were determined by Pico Green DNA assays and alkaline phosphatase (ALP) activity, respectively. All hydroxyapatite–bioglass co-sintered ceramics exhibited larger cell proliferation compared to pure hydroxyapatite samples. After 6 days in cell culture, the ceramic with Ca₅(PO₄)₃SiO₄ in a silicate matrix formed by reacting hydroxyapatite with 10 wt.% bioglass exhibited the maximum proliferation of the BMSC's. The ALP activity was found to be largest in the ceramic with Na₃Ca₆(PO₄)₅ embedded in a silicate matrix synthesized by reacting hydroxyapatite with 25 wt.% bioglass.     

Substitution of manganese and iron into hydroxyapatite: Core/shell nanoparticles

The bioceramics, hydroxyapatite (HAP), is a material which is biocompatible to the human body and is well suited to be used in hyperthermia applications for the treatment of bone cancer. We investigate the substitution of iron and manganese into the hydroxyapatite to yield ceramics having the empirical formula Ca_9.4Fe_0.4Mn_0.2(PO₄)₆(OH)₂. The samples were prepared by the co-precipitation method. The formation of the nanocrystallites in the HAP structure as the heating temperatures were raised to obtain a glass–ceramic system are confirmed by X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron diffraction (ED) and electron spin resonance (ESR). TEM images show the core/shell structure of the nanoparticles, with the core being formed by the ferrites and the shell by the hydroxyapatite. The ED patterns indicate the nanoparticles formed at 500 °C have an amorphous structure while the nanoparticles formed at 1000 °C are crystalline. ESR spectroscopy indicated that the Fe³⁺ ions have a g-factor of 4.23 and the Mn²⁺ ions have a g-factor of 2.01. The values of the parameters in the spin Hamiltonian which describes the interaction between the transition metal ions and the Ca²⁺ ions, indicate that the Mn²⁺ ion substitute into the Ca²⁺ sites which are ninefold coordinated, i.e., the Ca(1) sites.     

Formulation and characterization of glass–ceramics based on Na2Ca2Si3O9–Ca5(PO4)3F–Mg2SiO4-system in relation to their biological activity

Glasses having a chemical composition based on combeite [Na₂Ca₂Si₃O₉]–fluoroapatite [Ca₅(PO₄)₃F] and forsterite [Mg₂SiO₄] system were crystallized through controlled heat-treatment. Two forms of sodium calcium silicate e.g. combeite Na₂Ca₂Si₃O₉ and pectolite Na₂CaSi₃O₈, were formed together with diopside (CaMgSi₂O₆) and monticellite (CaMgSiO₄) in addition to fluoroapatite (Ca₅(PO₄)₃F) phases by thermal treatment of the glasses. Selected glass–ceramics were exposed to a simulated body fluid solution (SBF) which is close to human plasma for 3 weeks. Energy dispersive X-ray analysis (EDX) and inductive coupled plasma (ICP) analysis confirmed the formation of an apatite layer which indicate bioactivity in the all crystallized sample. A decreasing of surface bioactivity with increasing Mg₂SiO₄/Na₂Ca₂Si₃O₉ replacement was observed as indicated by the decrease in the amount of apatite layer on the surface of the crystallized specimens. The Vicker’s microhardness of the studied glass–ceramic materials are between 5,047 and 6,781 MPa.     

Tunable luminescence properties and energy transfer of single-phase Ca<Subscript>4</Subscript>(PO<Subscript>4</Subscript>)<Subscript>2</Subscript>O: Dy<Superscript>3+</Superscript>, Eu<Superscript>2+</Superscript> multi-color phosphors for warm white light

The novel Ca_4?x(PO₄)₂O: xDy³⁺ and Ca_4?x?y(PO₄)₂O: xDy³⁺, yEu²⁺ multi-color phosphors were synthesized by traditional solid-state reaction. The crystal structure, particle morphology, photoluminescence properties and energy transfer process were investigated in detail. The X-ray diffraction (XRD) results demonstrate that the products showed pure monoclinic phase of Ca₄(PO₄)₂O when x < 0.1. The scanning electron microscopy (SEM) indicated that the phosphors were grain-like morphologies with diameters of ~ 3.7–7.0 μm. Under excitation of 345 nm, Dy³⁺-doped Ca₄(PO₄)₂O phosphors showed multi-color emission bands at 410, 481 and 580 nm originated from oxygen vacancies and Dy³⁺. Interestingly, Ca₄(PO₄)₂O: Dy³⁺, Eu²⁺ phosphors exhibited blue emission band at 481 nm and broad emission band from 530 to 670 nm covering green to red regions. The energy transfer process from Dy³⁺ to Eu²⁺ was observed for the co-doped samples, and the energy transfer efficiency reached to 60% when Eu²⁺ molar concentration was 8%. In particular, warm/cool/day white light with adjustable CCT (2800–6700 K) and high CRI (R_a > 85) can be obtained by changing the Eu²⁺ co-doping contents in Ca₄(PO₄)₂O: Dy³⁺, Eu²⁺ phosphors. The optimized Ca_3.952(PO₄)₂O: 0.04Dy³⁺, 0.008Eu²⁺ phosphor can achieve the typical white light with CCT of 4735 K and CRI of 87.     

Improvement of alkali corrosion resistance of mullite ceramics at high temperature by depositing Ca0.3Mg0.2Zr2(PO4)3 coating

Ca_0.3Mg_0.2Zr₂(PO₄)₃ coating was deposited on the mullite ceramic to improve its alkali corrosion resistance at high temperatures, using sol–gel method and dip-coating technique. The phase composition and microstructure of the coating were characterized by X-ray diffraction and scanning electron microscopy (SEM). Results show that homogeneous, dense and single-phase Ca_0.3Mg_0.2Zr₂(PO₄)₃ coating was successfully deposited on mullite ceramics. SEM microstructural examination revealed the excellent bonding between Ca_0.3Mg_0.2Zr₂(PO₄)₃ coating and mullite ceramics. The effectiveness of the prepared coating to improve the alkali corrosion resistance of mullite ceramics was assessed through the measurements of mass loss and flexural strength degradation after 96 h and longer exposure time at alkali corrosion condition at 1000 °C. A significant enhancement of the alkali corrosion resistance for Ca_0.3Mg_0.2Zr₂(PO₄)₃-coated mullite samples was observed. Therefore, the effectiveness of the Ca_0.3Mg_0.2Zr₂(PO₄)₃ material as protection coating for mullite ceramic is confirmed.