Bone-like Hydroxyapatite Research Articles

Comparative study of hydroxyapatite synthesized using Schiff base and wet chemical precipitation methods

Hydroxyapatite (HAp) exists as an inorganic and crystalline composition present in bones and dental enamel, and hence can be utilized as a direct element or as part of the composition of biomaterials and implants for dental and orthopaedic applications. Listed below are a few synthesis techniques for HAp that are listed in the literature: solid-state and mechano-chemical methods (dry methods), wet chemical precipitation and sol-gel methods (wet methods), and combustion and pyrolysis methods (high-temperature processes). Nevertheless, there are new and more productive techniques that result in HAp with a regulated morphology, such as the Schiff base method, which, on reaction with calcium and phosphate precursors, forms chelating complexes to produce HAp nuclei. This research paper presents the comparison in characteristics between HAp synthesized using Schiff base (HAp-SB), wet chemical precipitation (HAp-WC) methods, and commercial HAp (HAp-CM) in their powdered and pelleted form. The average size of HAp-WC particles in the spherical form was found to be 603 nm ± 176, HAp-SB were found to have rod-like morphology, which is very similar to human bone-like HAp, with an average length and width of 1522 nm ± 759 and 400 nm ± 112, respectively, and HAp-CM were found to have spherical morphology with dimensions of 52 nm ± 25. Biological studies show that cell viability of HAp-SB pellet (202.01% ± 8.16) seemed to have higher cell proliferation properties than HAp-WC pellet (145.7% ± 5.11) and HAp-CM pellet (71.53% ± 3.61) due to its higher aspect ratio, and hence higher surface area for the cells to adhere. In a detailed study, it is observed that both techniques had their advantages, and there were no significant disadvantages observed.

Enhanced in-vitro biodegradation, bioactivity, and mechanical properties of Mg-based biocomposite via addition of calcium-silicate-based bioceramic through friction stir processing as resorbable temporary bone implant

Bioabsorbable Mg and alloys have been used as metallic biomaterials for orthopedic implant applications due to their similar mechanical properties to human natural bone. High biodegradation rate is the main reason for limiting clinical applications of Mg and alloys in biological media. In order to achieve long-lasting bio applications of bioabsorbable WE43 Mg alloy, it is necessary to improve strength and bioactivity and control biodegradation rate of this material. In this study, Mg-based biocomposites are produced using friction stir processing (FSP) by addition of wollastonite (CaSiO3) calcium-silicate-based bioactive reinforcing particle into Mg matrix. The results showed that applied severe plastic deformation during FSP caused formation of ultra-fine grain structure with homogenous distribution of secondary phase particles, which resulted in a remarkable improvement of ductility, strength and load bearing capacity of FSPed Mg matrix. Also, biodegradation behavior of resulting biocomposite was evaluated using electrochemical methods and in-vitro immersion test in simulated body fluid (SBF) and phosphate-buffered saline (PBS) at 37.5 °C. The results revealed that processed bioabsorbable Mg alloy showed a lower biodegradation rate compared to monolithic Mg alloy. Furthermore, the presence of wollastonite bioceramic particles significantly enhanced strength and reduced biodegradation of the Mg-based biocomposite. Moreover, the addition of wollastonite bioceramic particles positively affected the bioactivity of Mg matrix by forming a cauliflower shaped bone-like hydroxyapatite layer on the surface after 28 days of immersion in SBF and stimulate bone tissue regeneration.

A NOVEL SPHEROIDAL PROGENITOR CELL DIFFERENTIATION AND BONE-LIKE IN VITRO BIOMINERALIZATION MODEL

Many age-related diseases affect our skeletal system, but bone health-targeting drug development strategies still largely rely on 2D in vitro screenings. We aimed at developing a scaffold-free progenitor cell-based 3D biomineralization model for more physiological high-throughput screenings.MC3T3-E1 pre-osteoblast spheroids were cultured in V-shaped plates for 28 days in alpha-MEM (10% FCS, 1% L-Gln, 1X NEAA) with 1% pen/strep, changed every two days, and differentiation was induced by 10mM b-glycerophosphate and 50µg/ml ascorbic-acid. Osteogenic cell differentiation was assessed through profiling mRNA expression of selected osteogenic markers by efficiency corrected normalized 2^DDCq RT-qPCR. Biomineralization in spheroids was evaluated by histochemistry (Alizarin Red/von Kossa staining), Alkaline phosphatase (Alp) activity, Fourier transform infrared spectroscopy (FTIR) analyses, micro-CT analyses, and scanning electron microscopy on critical point-dried samples. GraphPad Prism 9 analyses comprised Shapiro-Wilk and Brown-Forsythe tests as well as 2-way ANOVA with Tukey post-hoc and non-parametric Kruskal-Wallis with Dunn post-hoc tests.During mineralization, as opposed to non-mineralizing conditions, characteristic mRNA expression profiles of selected early and late osteoblast differentiation markers (e.g., RunX, Alp, Col1a1, Bglap) were observed between day 0 and 28 of culture; Alp was strongly upregulated (p<0.001) from day 7 on, followed by its enzymatic activity (p<0.001). Bglap and Col1a1 expression peaked on (p<0.001) and from day 14 on (p<0.05), respectively. IHC revealed osteocalcin staining in the spheroid core regions at day 14, while type I collagen staining of the cores was most prominent from day 21 on. Alizarin Red and Von Kossa confirmed central and radially outwards expanding mineralization patterns between day 14 and day 28, which was accompanied by a steady increase in extracellular calcium deposition over time (p<0.001). Micro-CT analyses allowed quantitative appreciation of the overall increase in mineral density over time (day21, p<0.05; d28, p<0.001), while SEM-EDX and FTIR ultimately confirmed a bone-like hydroxyapatite mineral deposition in 3D.A novel and thoroughly characterized versatile bone-like 3D biomineralization in vitro model was established, which allows for studying effects of pharmacological interventions on bone mineralization ex vivo under physiomimetic conditions. Ongoing studies currently aim at elucidating in how far it specifically recapitulates intramembranous ossification.

Bone ECM-inspired biomineralization chitin whisker liquid crystal hydrogels for bone regeneration

As a particular cell niche, natural bone extracellular matrix (ECM) is an organic-inorganic composite material formed by mineralization of liquid crystal (LC) collagen fiber network. However, designing bone repair materials that highly imitate the LC characteristic and composite components of natural bone ECM is a great challenge. Here, we report a novel kind of bone ECM-inspired biomineralization chitin whisker LC hydrogels. First, photocurable chitin whisker LC hydrogels with bone ECM-like chiral nematic LC state and viscoelasticity are created. Next, biomineralization, guided by LC hydrogels, is carried out to truly mimic the mineralization process of natural bone, so as to obtain the organic-inorganic composite materials with bone ECM-like microenvironment. The chitin whisker LC hydrogels exhibit superior biomineralization, protein adsorption and osteogenesis ability, more importantly, LC hydrogel with negatively charged –COOH groups is more conducive to biomineralization and shows more desirable osteogenic activity than that with positively charged –NH2 groups. Notably, compared with the pristine LC hydrogels, the biomineralization LC hydrogels display more favorable osteogenesis ability due to their bone ECM-like LC texture and bone-like hydroxyapatite. This study opens an avenue toward the design of bone ECM-inspired biomineralization chitin whisker LC hydrogels for bone regeneration.

In Situ Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration

A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic-inorganic cocross-linking, here, we built a strong organic-inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the in situ mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement in vitro. The BOH exhibited acceleration of osteogenesis in vivo, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The in situ mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic-inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.

10XSBF Bone-Like Hydroxyapatite Coating of Ti–6Al–4V with Microwave Irradiation and its Antibacterial Properties

10XSBF Bone-Like Hydroxyapatite Coating of Ti–6Al–4V with Microwave Irradiation and its Antibacterial Properties

Biomineralization of bone-like hydroxyapatite to upgrade the mechanical and osteoblastic performances of poly(lactic acid) scaffolds

Biomimetic mineralization of high-strength apatite structure essentially relies on mimicking the inorganic building blocks of naturally occurring bones. However, conventional routes still have substantial function gaps in providing precision control over the geometrical dimensions and crystalline morphology of biomineralized apatite. Herein, we conceived the concept of microwave-assisted biomineralization (MAB) to customize 1D hydroxyapatite nanowhiskers (HANWs) at graphene templates, rendering the formation of graphene-hydroxyapatite (Gr-HA) nanohybrids. The HANWs essentially resembled bone apatite in elemental composition (Ca/P = 1.74), diameter (~20 nm), crystallinity (63 %), and rodlike geometry (aspect ratio of ~6). The Gr-HA nanohybrids were uniformly incorporated into poly(lactic acid) (PLA) microfibers (~1 μm) by electrospinning, engendering fibrous membranes with a set of Gr-HA loadings (10, 20 and 30 wt%). Intimate interactions were generated between Gr-HA and PLA matrix, contributing to significant promotion of the mechanical properties for PLA composite membranes. For example, the yield strength and elastic modulus of the PLA composite membranes loaded with 30 wt% Gr-HA achieved 5.4 and 66.4 MPa, increasing nearly 182 % and over 94 % compared to those of pure PLA, respectively. Moreover, the bone-like HANWs endowed PLA membranes with excellent cytocompatibility and good bioactivity, as demonstrated by over 38 % increase in cell viability and rapid apatite formation in mineral solution. The impressive combination of mechanical properties and biological characteristics make the PLA/Gr-HA scaffolds promising for guided tissue/bone regeneration therapy.

Self-biomineralized in situ injectable CaSO4 nanorods-enriched collagen-hyaluronic acid composite hydrogels for biomimetic bone reconstruction in a minimally invasive manner

In situ injectable natural polymer-based hydrogels can be utilized to fill irregular defects and promote tissue regeneration. However, most hydrogels showed limited ability for self-biomineralization and can not guide the formation of new bone. Herein, according to the challenges encountered in advancing materials to clinical research, an injectable collagen-hyaluronic acid (Col-HA) hydrogel embedded with calcium sulfate nanorods (CSN) was developed via a bio-orthogonal reaction between norbornene (Nb) and tetrazine (Tz). The formulated CSN@Col-HA composite hydrogels not only have the potential to enhance cell adhesion and proliferation, but also serve as the system to control Ca2+ release. This composite hydrogel displayed impressive injectability, allowing straightforward in situ injection and subsequent adaption of composite hydrogels to irregularly shaped bone defects. CSN-incorporated composite hydrogels facilitate self-biomineralization, thereby fast-forming bone-like hydroxyapatite (HAp) within the hydrogel. Furthermore, Ca2+ released in a steady and sustained way from the composite hydrogels stimulated the differentiation of preosteoblasts, and promoted in situ bone growth. Our findings suggested that CSN@Col-HA composite hydrogels can successfully mediate the optimized CSN degradation, effectively accelerate HAp formation, and boost in situ bone development via the minimally invasive application.

Ra-223 induces clustered DNA damage and inhibits cell survival in several prostate cancer cell lines

The bone-seeking radiopharmaceutical Xofigo (Radium-223 dichloride) has demonstrated both extended survival and palliative effects in treatment of bone metastases in prostate cancer. The alpha-particle emitter Ra-223, targets regions undergoing active bone remodeling and strongly binds to bone hydroxyapatite (HAp). However, the toxicity mechanism and properties of Ra-223 binding to hydroxyapatite are not fully understood. By exposing 2D and 3D (spheroid) prostate cancer cell models to free and HAp-bound Ra-223 we here studied cell toxicity, apoptosis and formation and repair of DNA double-strand breaks (DSBs). The rapid binding with a high affinity of Ra-223 to bone-like HAp structures was evident (KD= 19.2 × 10−18 M) and almost no dissociation was detected within 24 h. Importantly, there was no significant uptake of Ra-223 in cells. The Ra-223 alpha-particle decay produced track-like distributions of the DNA damage response proteins 53BP1 and ɣH2AX induced high amounts of clustered DSBs in prostate cancer cells and activated DSB repair through non-homologous end-joining (NHEJ). Ra-223 inhibited growth of prostate cancer cells, independent of cell type, and induced high levels of apoptosis. In summary, we suggest the high cell killing efficacy of the Ra-223 was attributed to the clustered DNA damaged sites induced by α-particles.

Modelling the Mechanical Properties of Hydroxyapatite Scaffolds Produced by Digital Light Processing-Based Vat Photopolymerization

Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.

Physiological Mineralization during In Vitro Osteogenesis in a Biomimetic Spheroid Culture Model.

Bone health-targeting drug development strategies still largely rely on inferior 2D in vitro screenings. We aimed at developing a scaffold-free progenitor cell-based 3D biomineralization model for more physiological high-throughput screenings. MC3T3-E1 pre-osteoblasts were cultured in α-MEM with 10% FCS, at 37 °C and 5% CO2 for up to 28 days, in non-adherent V-shaped plates to form uniformly sized 3D spheroids. Osteogenic differentiation was induced by 10 mM β-glycerophosphate and 50 µg/mL ascorbic acid. Mineralization stages were assessed through studying expression of marker genes, alkaline phosphatase activity, and calcium deposition by histochemistry. Mineralization quality was evaluated by Fourier transformed infrared (FTIR) and scanning electron microscopic (SEM) analyses and quantified by micro-CT analyses. Expression profiles of selected early- and late-stage osteoblast differentiation markers indicated a well-developed 3D biomineralization process with strongly upregulated Col1a1, Bglap and Alpl mRNA levels and type I collagen- and osteocalcin-positive immunohistochemistry (IHC). A dynamic biomineralization process with increasing mineral densities was observed during the second half of the culture period. SEM–Energy-Dispersive X-ray analyses (EDX) and FTIR ultimately confirmed a native bone-like hydroxyapatite mineral deposition ex vivo. We thus established a robust and versatile biomimetic, and high-throughput compatible, cost-efficient spheroid culture model with a native bone-like mineralization for improved pharmacological ex vivo screenings.

Programmable, biodegradable composite scaffolds with variable pore morphology for minimal invasive bone repair

Tissue engineered biocompatible scaffolds could mimic the natural bone structure for cell adhesion and proliferation, however, patients suffer from large volume implantation. In this study, a porous composite biocompatible bone scaffold based on shape memory polymer materials (SMP) was developed from poly(ε-caprolactone) (PCL) diol, hexamethylene diisocyanate (HDI) and hydroxyapatite (HA). The prepared shape memory composite scaffold presented good pore connectivity, high porosity, good mechanical and biological properties. Additionally, after programming to a temporary shape, the scaffolds could recover to the initial shape, filling the site of bone defect. Moreover, HA improved the mechanical properties of scaffolds, promoted cell adhesion and influencing the shape recovering speed. During in vitro mineralization, HA could promote the formation and deposition of bone-like hydroxyapatite and accelerate the repair of damaged tissues, no inflammatory problem occurred after the in vivo implantations. These programmable scaffolds could be applied in minimal invasive bone repair.

Biodegradation behavior of polymethyl methacrylate−bioactive glass 45S5 composite coated magnesium in simulated body fluid

The biodegradation behavior of Mg, coated by polymethyl methacrylate as well as polymethyl methacrylate (PMMA)−bioactive glass (BG) composite was investigated. Electrophoretic deposition and dip coating techniques were adopted to prepare composite coating using a suspension of different percentages of the above two chemical materials. The deposited coatings were characterized using SEM, EDS, FTIR, and water contact angle measurements. Biodegradation behavior study of the coated Mg was performed using linear polarization, impedance spectroscopy, and immersion tests in simulated body fluid. The compact and homogeneous composite coating was developed as evidenced by electron microscopy results. The water contact angle measurement showed a 44° increase in the contact angle of the composite coated Mg compared to the uncoated one. The composite coating was covered by a bone-like hydroxyapatite layer after 336 h, indicating that the coating has an excellent in vitro bioactivity. The electrochemical testing results confirmed a significant reduction, 96.9%, in the biodegradation rate of Mg coated with the composite prepared from 45 g/L PMMA + 3.5 g/L 45S5 GB suspension compared to that of the uncoated one. Therefore, the composite coated Mg can be proposed as a promising material for biodegradable implant application.

An intrinsic analysis on the nature of alumina (Al2O3) reinforced hydroxyapatite nanocomposite

Human bones possess a unique capacity to regenerate and regrow. Bone implants are used to support the body and provide time for the bones to heal. Amidst expensive and incompatible bone implants, bone-like hydroxyapatite (HA) is considered as a perfect choice, but its brittle nature makes it unfit. This study aims to rectify this issue, by reinforcing HA with alumina (Al2O3). Hydrothermal method was adopted to form the Al2O3/HA nanocomposite. X-ray Diffraction (XRD) and Fourier-Transform Infra-Red (FTIR) spectroscopy tests validate the basal structure and constitution of the Al2O3/HA nanocomposite. Imaging tests revealed nanorod morphology and thermogravimetric-differential thermal analysis revealed the thermal nature of Al2O3/HA. The mechanical stability of the nanocomposite was scrutinized by a Vicker's hardness tester. Load-displacement curve analyses by means of Onitsch and Kick's power laws were used to find various mechanical parameters. The enhanced nanocomposite proved to be sturdy with a hardness value of 5.2 GPa and a fracture toughness of 1.18 MPam1/2. Thereby, the addition of alumina was found to be advantageous in resolving the brittleness issue of HA.

Highly bioactive bone cement microspheres based on α-tricalcium phosphate microparticles/mesoporous bioactive glass nanoparticles: Formulation, physico-chemical characterization and in vivo bone regeneration

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing α-tricalcium phosphate microparticles (α-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The α-TCP microparticles were prepared by a solid state synthesis at 1400 ºC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 – 450 µm with a sphericity index in the range of 0.92 – 0.94. The surface morphology of α-TCP microspheres revealed α-TCP micoparticles with smooth surfaces whereas α-TCP/BGn microspheres unveiled nano-roughened α-TCP microparticles. The as-prepared α-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO44-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the α-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared α-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations.

Bone-like hydroxyapatite anchored on alginate microspheres for bone regeneration

Inspired by the initial mineralization process in bone matrix vesicles (MVs), we used Dulbecco's Modified Eagle's Medium (DMEM) to establish the similar physiological environment to that in MVs for biomimetic mineralization on alginate (ALG) microspheres. The results showed that HA crystals were firstly formed and anchored on the membrane of microspheres like the initial deposition of hydroxyapatite crystals inside MVs. With the continuous growth and accumulation of mineral crystals, HA coating was finally formed on ALG microspheres. The mineralized ALG microspheres (M-ALG microspheres) show good biocompatibility and osteogenic performance. The HA coating is also conducive to the active migration of osteoblasts to the surface of M-ALG microspheres. Collectively, bone-like HA crystals anchored on ALG microspheres may provide a good prospect to promote the repair of bone defects.

Hydroxyapatite Particles from Simulated Body Fluids with Different pH and Their Effects on Mesenchymal Stem Cells.

Bone-like hydroxyapatite (HAp) has been prepared by biomimetic synthesis using simulated body fluid (SBF), mimicking inorganic ion concentrations in human plasma, or 1.5SBF that has 1.5-times higher ion concentrations than SBF. In this study, the controllable preparations of HAp particles from 1.5SBF with different pH values were examined. The particles obtained as precipitates from 1.5SBF showed different morphologies and crystallinities depending on the pH of 1.5SBF. Micro-sized particles at pH 7.4 of 1.5SBF had a higher Ca/P ratio and crystallinity as compared with nano-sized particles at pH 8.0 and pH 8.4 of 1.5SBF. However, a mixture of micro-sized and nano-sized particles was obtained from pH 7.7 of 1.5SBF. When Ca2+ concentrations in 1.5SBF during mineralization were monitored, the concentration at pH 7.4 drastically decreased from 12 to 24 h. At higher pH, such as 8.0 and 8.4, the Ca2+ concentrations decreased during pH adjustment and slightly decreased even after 48 h. In this investigation at pH 7.7, the Ca2+ concentrations were higher than pH 8.0 and 8.4.Additionally, cytotoxicity of the obtained precipitates to mesenchymal stem cells was lower than that of synthetic HAp. Controllable preparation HAp particles from SBF has potential applications in the construction of building components of cell scaffolds.

A new biocompatible phosphate free mesoporous calcium borosilicate glass-ceramics for medical application

Boron plays an important role in life processes such as bone growth and maintenance. Structural and bioactivity properties of phosphate free novel composition of calcium borosilicate mesoporous glass–ceramic is reported. X-ray diffraction studies indicate the amorphous nature of sample and Fourier transmission infrared spectroscopy reveal the possible bending and stretching vibration modes of silicate and borate groups. N2 adsorption–desorption studies reveal the mesoporous structure with average pore diameter of 28 nm and surface area of 101 m2 g−1. The sample exhibits good bone-like hydroxyapatite layer formation after soaking in stimulated body fluids. Biocompatibility test of sample carried out by using myoblasts cell derived from muscle of mouse indicates an excellent biocompatibility.

Sol-gel synthesis and characterization of novel cobalt ions-containing mesoporous bioactive glass nanospheres as hypoxia and ferroptosis-inducing nanotherapeutics

Herein, novel Co2+ ions-containing mesoporous bioactive glass nanospheres (Co-BGn) with low and high cobalt contents were prepared by a facile one-pot ultrasonic-coupled sol-gel synthesis. Structural evaluations revealed that Co-BGn are totally amorphous and cobalt ions exist as Co2+ ions in the glass structure. Notably, Co-BGn exhibited uniform spherical morphology, nanosize (< 100 nm), high worm-like mesoporosity (0.41 cm3/g) and large specific surface area ca. 787.5 m2/g. Interestingly, low and high Co-BGn showed sustained release of Co2+ ions with controlled release (8 – 32 ppm) and fast release (54 – 112.5 ppm) kinetics over 2 weeks, respectively. Furthermore, Co-BGn showed good bone-like hydroxyapatite formation in vitro. Accordingly, low Co-BGn with controlled release of Co2+ ions can be considered as hypoxia-mimic nanotherapeutics for bone/skin tissue regeneration. Whereas, high Co-BGn with fast release of high concentrations of Co2+ ions can be considered for ferroptosis killing of cancer cells including bone and skin cancers.

Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: Structural, physico-chemical, catalase-mimic and biological properties

The multifunctional biological properties of Ce ions including antioxidant, anti-inflammatory, antibacterial and anti-cancer effects are very encouraging for development of Ce-containing biomaterials with therapeutic properties. Herein, novel Ce3+/Ce4+ ions containing mesoporous bioactive glass ultrasmall nanoparticles (Ce-BGn) were prepared by a facile one-pot ultrasound-assisted sol-gel method. Interestingly, Ce2O3 incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn (SiO2 – CaO binary glass system). Ce-BGn exhibited ultrasmall nanoparticle size (< 30 nm), mesoporous texture (pore size up to 2.82 nm and pore volume up to 0.191 cm3/g) and large specific surface area ca. 132.9 m2/g. Notably, in situ formation of CeO2 nanospheres (3–6 nm) was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. Importantly, X-ray photoelectron spectroscopy (XPS) revealed the presence of 72.57 % Ce3+ and 27.43 % Ce4+ at the surface of mesoporous Ce-BGn with Ce3+/Ce4+ ratio = 2.66. Furthermore, mesoporous Ce-BGn exhibited high catalase-mimic activity and showed sustained release of Ce (2.5–32 ppm), Ca (85–327 ppm) and Si (54–200 ppm) ions within 4 weeks along with excellent bone-like hydroxyapatite formation. Finally, the in vitro biological behavior of mesoporous Ce-BGn in cell cultures of human skin fibroblasts (HSF) revealed that mesoporous Ce-BGn (with concentrations up to 300 μg/mL) possess good cyto-biocompatibility. Taken together, novel ultrasmall mesoporous Ce-BGn showed remarkable catalase-mimic activity via surface containing Ce3+/Ce4+ ions which can scavenge ROS (Ce3+↔ Ce4+) and decompose H2O2 molecules into H2O and O2. In addition to that, Ce-BGn demonstrated sustained release of bioactive ions (Ce, Ca and Si), excellent bone-like hydroxyapatite formation and good cyto-biocompatibility.