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Aim: In this study, we evaluated the effects of two types of hydroxyapatite (HAP) nanoparticles, sharing the same surface chemistry but differing in shape, on the biological characteristics of plasma, platelets and red blood cells. Materials & methods: Initially, two different shapes (rod-shaped and sphere-shaped) of HAPs were characterized. These HAPs were then co-cultured with plasma and red blood cells to examine their impact on coagulation and hemolysis. The impact of HAPs on white blood cells count in mice were evaluated following gavage and tail vein injection. Results: Sphere-shaped HAP is more likely to adsorb onto platelet surfaces, while rod-shaped HAP is more likely to cause hemolysis. Although there are differences in the in vitro experimental results between sphere-shaped HAP and rod-shaped HAP, both types demonstrate good blood compatibility at a 20 mM concentration. Furthermore, in vivo experiments showed that sphere-shaped nano-HAP induced a more pronounced increase in white blood cell count, suggesting that it may exhibit greater toxicity. Conclusion: While differences exist in the blood compatibility test results between the two HAPs, these differences are minimal, with both results falling within a safe range. Overall, HAP demonstrates excellent blood compatibility. Article highlights Despite the increasingly widespread application of nanoparticles in the biomedical field, the impact of nanoparticle shape on the biological characteristics of blood cells and plasma components remains inadequately characterized. To address this knowledge gap, we conducted a systematic evaluation of the biological effects of two hydroxyapatite (HAP) nanoparticle suspensions with different shapes (rod-shaped and sphere-shaped) but identical surface chemical properties on various blood components, including coagulation factors, platelets and red blood cells. Our findings demonstrated that these two HAP nanoparticles did not cause adverse reactions, such as plasma coagulation, platelet activation or red blood cell hemolysis at a concentration of 20 mM, indicating their good blood compatibility at this concentration. In vivo experiments at a dose of 500 μM/kg showed that both gastric lavage and tail vein injection of HAP induced an increase in white blood cell count in the experimental animals, indicating potential early and late inflammatory responses. [ABSTRACT FROM AUTHOR]

The photophysical properties and efficiency of photosensitized singlet oxygen formation by meso-tetrakis(4- N-methylpyridyl)porphyrin in a complex with hydroxyapatite nanoparticles were studied. At least three types of complexes characterized by different access of oxygen to porphyrin molecules were shown to form on the surface of the hydroxyapatite nanoparticles. Rotation of the pyridyl substituents of porphyrin in the complex with hydroxyapatite nanoparticles was found to be significantly hindered, while porphyrin molecules on the surface of the nanoparticles were in a less polar environment than in water. The quantum yield of photosensitized singlet oxygen formation was observed to decrease by at least nine times for porphyrin in the complex with hydroxyapatite nanoparticles. Porphyrin was released from hydroxyapatite nanoparticles and the efficiency of singlet oxygen formation increased although it did not reach the values characteristic for free porphyrin if the pH decreased to less than 5.0 (pH < 5.0). [ABSTRACT FROM AUTHOR]

Background: Differentiation of pluripotent stem cells into desired lineages is the key aspect of regenerative medicine and cell‐based therapy. Although RNA interference (RNAi) technology is exploited extensively for this, methods for long term silencing of the target genes leading to differentiation remain a challenge. Sustained knockdown of the target gene by RNAi is often inefficient as a result of low delivery efficiencies, protocol induced toxicity and safety concerns related to viral vectors. Earlier, we established octa‐arginine functionalized hydroxyapatite nano vehicles (R8HNPs) for delivery of small interfering RNA (siRNA) against a pluripotency marker gene in mouse embryonic stem cells. Although we demonstrated excellent knockdown efficiency of the target gene, sustained gene silencing leading to differentiation was yet to be achieved. Methods: To establish a sustained non‐viral gene silencing protocol using R8HNP, we investigated various methods of siRNA delivery: double delivery of adherent cells (Adh‐D), suspension delivery followed by adherent delivery (Susp + Adh), single delivery in suspension (Susp‐S) and multiple deliveries in suspension (Susp‐R). Sustained knockdown of a pluripotent marker gene followed by differentiation was analysed by reverse transcriptase‐PCR, fluoresence‐activated cell sorting and immunofluorescence techniques. Impact on cell viability as a result of repeated exposure of the R8HNP was also tested. Results: Amongst the protocols tested, the most efficient knockdown of the target gene for a prolonged period of time was obtained by repeated suspension delivery of the R8HNP‐siRNA conjugate. The long‐term silencing of a pluripotency marker gene resulted in differentiation of R1 ESCs predominantly towards the extra embryonic and ectodermal lineages. Cells displayed excellent tolerance to repeated exposures of R8HNPs. Conclusions: The results demonstrate that R8HNPs are promising, biocompatible, non‐viral alternatives for prolonged gene silencing and obtaining differentiated cells for therapeutics. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAp) nanoparticles organically modified with citrate group are fabricated via a simple wet chemical precipitation method. The as-synthesized nanoparticles are structurally characterized by TEM, XRD, FT-IR, EDAX and dynamic light scattering (DLS) to investigate in detail the influence of surface coating ligand i.e. citrate on HAp morphology, crystal structure, phase and colloidal stability of the particles. Production of single phase with hexagonal crystal structure is evident by XRD analysis. The work shows mesoporous structure could be synthesized under the influence of citrate as confirmed by TEM image and N2 adsorption−desorption isotherm. The experimental results indicate that citrate strongly influences HAp crystallization giving reduced particle size and uniform distribution. BET and BJH analysis indicate large surface area 135.74 m2/g and pore diameter of 9.86 nm with a total pore volume of 0.41 cm3/g respectively for 1 : 1 citrate to calcium ion molar ratio. The appropriate surface area and pore entrance significantly indicate potentiality to apply into biomedical fields as drug loading/delivery application. [ABSTRACT FROM AUTHOR]

Purpose: The main purposes of this study were to explore a unique approach for producing nano-hierarchical morphological hydroxyapatite (n-HA) and to evaluate its potential applications in the field of biomedicine, specifically in orthopedics and orthodontics. The research question was whether using glucose 6-phosphate biomolecules as an organic phosphorus source through the pulsed ultrasonic process could generate n-HA nanoparticles with exceptional morphology. Methods: The researchers employed the pulsed ultrasonochemical process to produce n-HA nanoparticles. The morphologies of the nanoparticles were examined using SEM and TEM techniques. The phase, structure, and composition of the nanoparticles were analyzed through DLS, XRD, XPS, and FTIR spectroscopic techniques. Biological evaluation experiments were conducted to assess the survivability and adhesion of the n-HA nanoparticles to osteoblast cells. Results: The study found that the morphologies of the n-HA nanoparticles generated varied significantly with alterations in the pulsed ultrasonic settings. SEM and TEM analyses provided visual evidence of the unique nano-hierarchical morphology of the nanoparticles. DLS, Zeta potential, XRD, XPS, and FTIR spectroscopy techniques confirmed the phase, structure, and composition of the n-HA nanoparticles. The biological evaluation experiments indicated that the nanoparticles exhibited favorable survivability and adhesion to osteoblast cells. Conclusions: This study successfully developed a method for producing nano-hierarchical morphological hydroxyapatite using glucose 6-phosphate biomolecules as an organic phosphorus source through the pulsed ultrasonochemical process. The n-HA nanoparticles generated displayed exceptional morphology and exhibited favorable survivability and adhesion to osteoblast cells. Therefore, these nanoparticles hold promise for potential applications in biomedical fields, particularly in orthopedics and orthodontics. [ABSTRACT FROM AUTHOR]

IntroductionThis study examined the efficacy of a therapy based on a combination of Platelet Rich Plasma and hydroxyapatite nanoparticles in a severe clinical case involving a young Rottweiler with a complex spiral fracture of the tibia.MethodFollowing a worsening of the lesion after traditional surgical intervention, the subject was treated with the combined therapy. X-rays were taken at the following stages: immediately post-surgery, four weeks post-surgery, and 10 days post-treatment. Fracture gap and callus density measurements were obtained using ImageJ analysis, allowing for a detailed quantitative assessment of bone regeneration over time.ResultsPost-operative radiographs indicated a clinical worsening of the fracture, revealing an increased fracture gap due to bone loss. However, significant improvements were observed ten days following the treatment, with a marked reduction in fracture gaps and increased callus density. These results demonstrated a notable acceleration in bone healing and callus formation compared to typical recovery times for similar lesions.ConclusionThe method showed potential for enhancing osteogenic regeneration, facilitating faster healing of serious orthopedic injuries compared to traditional methods.

AbstractBiocompatible high internal phase emulsions (HIPEs) have attracted much attention in food and cosmetics due to their unique properties, such as adjustable viscoelasticity, high nutrient load, and long shelf life. Herein, we report an olive oil-in-water high internal phase Pickering emulsion (HIPE) stabilized solely by bare hydroxyapatite (HA) nanoparticles. Compared with other HIPEs, the HIPEs stabilized by HA nanoparticles could be obtained through a one-step emulsification method without chemical modification or other chemical additives. The increase of HA concentration (≥ 0.5 wt%) resulted in increases in both the storage modulus and loss modulus of the HIPEs, indicating the particle network plays an essential role in the HIPEs gel strength. After increasing the oil phase fraction from 80% to 90%, the viscosity of the HIPEs increased from 8316 to 13855 Pa⋅s (shear rate 0.004 s−1) and exhibited as a pseudoplastic fluid. The effect of oil type on the HIPEs was also investigated. The HA nanoparticles may interact with the olefin and carbonyl groups of olive oil, forming interfacial-active particles to stabilize the HIPEs. This method is universal as it occurs with other natural oils (soybean, sunflower, and fish oil), which may have various applications in food, cosmetics, and functional material fields. [ABSTRACT FROM AUTHOR]

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV–visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future. [ABSTRACT FROM AUTHOR]

An injectable and biodegradable drug delivery system to release antibiotics at a controllable rate to treat anti-bone infection was prepared. The system was based on nanocomposites of hydroxyapatite nanoparticles (HAP) and double-network hydrogels of sodium alginate (SA)/polyvinyl alcohol (PVA) prepared in the form of microspheres embedded in injectable agar gel. The double-network hydrogels of SA/PVA were prepared by sequential crosslinking of sodium alginate with calcium ions and then PVA by freeze-thawing method. The agar gel was used as a thermos-reversible gel to facilitate injection of microspheres. The characteristics of microspheres were analyzed by FTIR, XRD, SEM and water swelling. The drug release rate of the microspheres was measured at various compositions of the delivery system components. The results showed that increase in PVA content of hydrogels led to a tighter double-network which consequently reduced the drug release rate. Loading of the drug into HAP nanoparticles as drug nano-containers, prolonged the drug release time from 1 to 6 days when the content of HAP nanoparticles was within the range of 2.5 to 5%. The antibacterial activities of the drug-loaded composite hydrogels were evaluated against E. coli bacteria by disk diffusion tests showing anti-bacterial effectiveness of such drug delivery systems. [ABSTRACT FROM AUTHOR]

Lead is one of the toxic heavy metals in the environment and its concentration in oceans, seas, lakes and rivers should be controlled. Both hydroxyapatite nanoparticles and gelatin were extracted from the bone wastes of Talang queenfish and were used for preparation of a hydroxyapatite‐gelatin nanocomposite. The nanocomposite was used as a modifier in fabrication of a carbon paste electrode (CPE) for determination of Pb2+ concentration. The behavior of the prepared electrode was studied with respect of changes in the amount of modifier and pH of the solution. The best response was obtained with 5 % wt of composite in CPE and at pH 5. The prepared electrode showed a linear response in the concentration range of 2–290 μM of Pb2+ with a good detection limit and acceptable stability, reproducibility and selectivity. The modified electrode showed an excellent selectivity towards Pb2+ in the presence of other metal ions such as Cd2+, Cu2+, Hg2+, Fe2+, Ni2+, Zn2+, Co2+ and Mg2+. The electrode can also be used for simultaneous determination of Cd2+, Cu2+ and Hg2+ without considerable interference with each other or Pb2+ ions. This electrode is convenient for determination of Pb2+ in real water samples without using a pre‐concentration step. [ABSTRACT FROM AUTHOR]

One of the most acute challenges in agriculture is to improve the efficiency of fertilisation to increase crop yields per unit area and simultaneously reduce climate and environmental footprints. Most soil based fertilisation strategies are remarkably inefficient due to chemical fixation, microbial immobilisation and leaching of nutrients to aqueous ecosystems. Nanofertilisation offers an attractive supplementary strategy as it allow us to manipulate the basic physico-chemical properties of mineral elements contained in nanoparticles and thereby bypass a range of those processes currently hampering an efficient uptake. Thus, bio-nanotechnology displays a range of emerging and fascinating possibilities, which pave the road to markedly improve nutrient use efficiency of both soil and foliar fertilisation. Here, we review how nanoparticles can be tailored with smart properties to better interact with root and leaf tissue for timely delivery of nutrients. Phosphorus fertilisation is used as a timely case to demonstrate how nanofertilisation can be developed to a stage where it can improve the poor phosphorus use efficiencies currently challenging modern agriculture on a global scale. [ABSTRACT FROM AUTHOR]

Abstract Background This study aims to synthesize and characterize hydroxyapatite nanoparticles (nano-HA) and evaluate their effects on the remineralization of demineralized enamel in the presence to Er,CR: YSGG laser irradiation. Materials and methods Enamel specimens from 44 human molars were divided into four groups: control, demineralized enamel, demineralized enamel treated with nano-HA, and demineralized enamel treated with nano-HA followed by Er,Cr:YSGG laser irradiation (0.5, 20 Hz, 60 µs, 20 s). Vickers microhardness test was used to evaluate the enamel surface hardness. The morphology and chemistry of enamel surfaces were assessed using scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Result The result of this study showed that the application of Er,CR: YSGG laser irradiation to demineralized enamel treated with nano-HA had the highest impact on its microhardness. Conclusion ER,CR: YSGG laser irradiation promotes enamel remineralization after treatment with nano HA.

Abstract Background Traditional phosphorus fertilizers generally have low efficiencies due to their immobilization in soil, and a large part of these fertilizers are not plant-available. Also, phosphorus resources are non-renewable. In recent years, a great deal of attention has been paid to nanofertilizers because of their slow or controlled release and also their very small particle size which increases the solubility and uptake of nanoparticles in plant. Hydroxyapatite nanoparticles are of great importance as phosphorus nanofertilizer thanks to their very low toxicity, biocompatibility, and the fact that products obtained from their degradation, i.e., phosphate and calcium ions, are naturally available in soils. Results In this study, hydroxyapatite nanoparticles were synthesized using the wet chemical precipitation method in three formulations and characterized with various techniques including electron microscopy, atomic force microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and elemental analysis. Chemical and microscopic analyses showed that phosphorus was distributed in different parts of the wheat (Triticum aestivum L.) plant. To investigate the fertilizing effects of the nanoparticles, hydroxyapatite nanoparticles were used in different culture media including alkaline soil, acidic soil, the mixture of peat moss and perlite, and cocopeat. Based on our observations, hydroxyapatite nanoparticles showed fertilizing properties in all media. However, fertilizing potential strongly depended on the culture media. HAP nanoparticles demonstrated a high potential to be used as a fertilizer in acidic media. Nevertheless, only a slight fertilizing effect was observed in alkaline soils. Furthermore, the findings of our study showed fertilizing properties of powder hydroxyapatite nanoparticles without the need to convert them to suspension. Moreover, hydroxyapatite nanoparticles in all the three formulations showed low toxicity in such a way that their toxicity was even less than that of triple super phosphate. Conclusions Hydroxyapatite nanoparticles in both suspension and powder forms can be considered an alternative to conventional phosphorus fertilizers in acidic culture media. Our study revealed that hydroxyapatite nanoparticles were likely dissolved in the culture media and absorbed by plant mainly in the phosphate form. Graphical Abstract

Chemical synthesis is one of the most employed methods to obtain crystalline hydroxyapatite nanoparticles. It is feasible to vary the synthesis conditions and study their effects on nanoparticle structure. In this work, hydroxyapatite nanoparticles were synthesised by a modified heat-treated precipitation method and varying stirring rate of the solution during the nucleation process. The main goal was to reduce the particle size without affecting the crystallinity degree of the synthesized material what is important for several use cases, such as biomedical applications. The produced materials were characterized by X-ray diffraction, Fourier transformed infrared spectroscopy, μ-Raman spectroscopy, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy and scanning electron microscopy. The nanoparticle’s size decreased by increasing the stirring rate during the nucleation step, showing that the employed synthesis method is efficient for obtaining hydroxyapatite nanoparticles of variable sizes without affecting the crystallinity degree.

Bone defects and injuries are challenging issues in regenerative medicine. Guided bone regeneration (GBR) techniques use biomaterials as scaffolds to support the healing of damaged bone tissue. In this context, there is growing interest in developing new biomaterials with bioabsorbable and bioactive properties to increase GBR effectiveness. In this study, composite corn starch/hydroxyapatite nanoparticle (HAp) biomembranes were synthesized to achieve bioresorbable and bioactive properties compatible with applications in GBR. Starch is a renewable source and presents suitable rheological properties for membrane preparation; in turn, HAp is well known for its osteogenic properties. The biomembranes were prepared by solvent casting (5 wt% aqueous corn starch suspension containing different amounts of HAp (i.e., 0, 2, 5, and 10% of the corn starch weight), to give the membranes HAp_0%, HAp_2%, HAp_5%, and HAp_10%, respectively). The physicochemical and biological properties of the biomembranes were assessed. The concentrations of up to 10% of HAp were homogeneously dispersed in the composite biomembranes. HAp addition increased the biodegradability and the ability of the biomembranes to release Ca2+. The biomembranes containing HAp were more mechanically resistant and less flexible and were not toxic to osteoblasts. Moreover, compared to pure corn starch biomembranes, osteoblasts adhered better to the composite biomembranes. The higher the HAp content, the greater the mineralization promoted by osteoblasts on the composite biomembranes. HAp addition also resulted in composite biomembranes with better fracture healing efficiency in vitro. Therefore, composite corn starch/HAp biomembranes have excellent characteristics, including biodegradability, bioactivity, mechanical strength, and biocompatibility, for the development of new materials aimed at GBR. [ABSTRACT FROM AUTHOR]

Background: This study aims to synthesize and characterize hydroxyapatite nanoparticles (nano-HA) and evaluate their effects on the remineralization of demineralized enamel in the presence to Er,CR: YSGG laser irradiation. Materials and methods: Enamel specimens from 44 human molars were divided into four groups: control, demineralized enamel, demineralized enamel treated with nano-HA, and demineralized enamel treated with nano-HA followed by Er,Cr:YSGG laser irradiation (0.5, 20 Hz, 60 µs, 20 s). Vickers microhardness test was used to evaluate the enamel surface hardness. The morphology and chemistry of enamel surfaces were assessed using scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Result: The result of this study showed that the application of Er,CR: YSGG laser irradiation to demineralized enamel treated with nano-HA had the highest impact on its microhardness. Conclusion: ER,CR: YSGG laser irradiation promotes enamel remineralization after treatment with nano HA. [ABSTRACT FROM AUTHOR]

Accumulating studies demonstrated that hydroxyapatite nanoparticles (HANPs) showed a selective anti-tumor effect, making them a good candidate for osteosarcoma (OS) treatment. However, the capacity of HANPs with different aspect ratios to regulate tumor immune microenvironment (TIM) was scarcely reported before. To explore it, the three HANPs with aspect ratios from 1.86 to 6.25 were prepared by wet chemical method. After a 24 or 72 h-exposure of OS UMR106 cells or macrophages to the nanoparticles, the tumor cells exhibited immunogenic cell death (ICD) indicated by the increased production of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), and macrophages were activated with the release of pro-inflammatory cytokines. Next, the beneficial crosstalk between tumor cells and macrophages generated in the presence of HANPs for improved anti-tumor immunity activation. In the OS-bearing cognate rat model, HANPs inhibited OS growth, which was positively correlated with CRT and HMGB1 expression, and macrophage polarization in the tumor tissues. Additionally, HANPs promoted CD8+ T cell infiltration into the tumor and systemic dendritic cell maturation. Particularly, HANPs bearing the highest aspect ratio exhibited the strongest immunomodulatory and anti-tumor function. This study suggested the potential of HANPs to be a safe and effective drug-free nanomaterial to control the TIM for OS therapy. Emerging studies demonstrated that hydroxyapatite nanoparticles (HANPs) inhibited tumor cell proliferation and tumor growth. However, the underlying anti-tumor mechanism still remains unclear, and the capacity of HANPs without any other additive to regulate tumor immune microenvironment (TIM) was scarcely reported before. Herein, we demonstrated that HANPs, in an aspect ratio-dependent manner, showed the potential to delay the growth of osteosarcoma (OS) and to regulate TIM by promoting the invasion of CD8+ T cells and F4/80+ macrophages, and inducing immunogenic cell death (ICD) in tumors. This work revealed the new molecular mechanism for HANPs against OS, and suggested HANPs might be a novel ICD inducer for OS treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

The insufficiently binder between acrylic teeth and dentures is considered to be the primary cause of teeth fractures from the dentures and is one of the disadvantages of acrylic denture base material. This research has been conducted to assess various concentrations of Nano hydroxyapatite addition on the shear bond between repaired acrylic teeth and polymer. One-hundred specimens of resin were split into two main subdivisions. 50 specimens were repaired with cold cured Duracryl Plus and the other 50 were repaired with a special type of acrylic O-cry1. Each one was sectioned into tested groups depending on (1%., 2%., 3%, and 5% by wt. of nano hydroxyapatite) incorporation and control group (0% of nano hydroxyapatite) with (n=10). The Universal testing machine was utilized for shear bond strength measurement. The obtained values were diffracted by t-test, ANOVA, and LSD-test. There was an increase in bond strength that repairing with O-cry1 than Duracryl Plus with a heightening in the bond strength, which was seen with incorporating nano hydroxyapatite into the acrylic resin with a significant difference between them. The 2% wt. Nano hydroxyapatite group demonstrated the maximum mean values, while those for the 5% wt. Nano hydroxyapatite group were recording minimum value with a significant difference between them. Repairing with O-cry1 recording better bond strength than Duracryl Plus acrylic. Furthermore, the addition of hydroxyapatite in Nano-form has successfully improved the "shear bond strength" of teeth to the PMMA at 2% wt. nano hydroxyapatite. [ABSTRACT FROM AUTHOR]

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV–visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Background: Traditional phosphorus fertilizers generally have low efficiencies due to their immobilization in soil, and a large part of these fertilizers are not plant-available. Also, phosphorus resources are non-renewable. In recent years, a great deal of attention has been paid to nanofertilizers because of their slow or controlled release and also their very small particle size which increases the solubility and uptake of nanoparticles in plant. Hydroxyapatite nanoparticles are of great importance as phosphorus nanofertilizer thanks to their very low toxicity, biocompatibility, and the fact that products obtained from their degradation, i.e., phosphate and calcium ions, are naturally available in soils. Results: In this study, hydroxyapatite nanoparticles were synthesized using the wet chemical precipitation method in three formulations and characterized with various techniques including electron microscopy, atomic force microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and elemental analysis. Chemical and microscopic analyses showed that phosphorus was distributed in different parts of the wheat (Triticum aestivum L.) plant. To investigate the fertilizing effects of the nanoparticles, hydroxyapatite nanoparticles were used in different culture media including alkaline soil, acidic soil, the mixture of peat moss and perlite, and cocopeat. Based on our observations, hydroxyapatite nanoparticles showed fertilizing properties in all media. However, fertilizing potential strongly depended on the culture media. HAP nanoparticles demonstrated a high potential to be used as a fertilizer in acidic media. Nevertheless, only a slight fertilizing effect was observed in alkaline soils. Furthermore, the findings of our study showed fertilizing properties of powder hydroxyapatite nanoparticles without the need to convert them to suspension. Moreover, hydroxyapatite nanoparticles in all the three formulations showed low toxicity in such a way that their toxicity was even less than that of triple super phosphate. Conclusions: Hydroxyapatite nanoparticles in both suspension and powder forms can be considered an alternative to conventional phosphorus fertilizers in acidic culture media. Our study revealed that hydroxyapatite nanoparticles were likely dissolved in the culture media and absorbed by plant mainly in the phosphate form. [ABSTRACT FROM AUTHOR]

Macrophages represent the most prevalent immune cells in the tumor micro-environment, making them an appealing target for tumor immunotherapy. One of our previous studies showed that hydroxyapatite nanoparticles (HANPs) enhanced Toll-like receptor 4 (TLR4) signal transduction in macrophages. This study was proposed to investigate how HANPs manipulated the phenotype and function of macrophage against 4T1 breast tumors in the presence or absence of MPLA, a low toxic Toll-like receptor 4 (TLR4) agonist. The results demonstrated that the addition of HANPs to MPLA significantly promoted cytokine secretion and macrophage polarization toward a tumoricidal M1 phenotype. Further, the resulting supernatant from HANPs/MPLA co-stimulated macrophages enhanced 4T1 tumor cells apoptosis compared to that from macrophages treated with a single component or PBS control. In particular, we found HANPs elicited immunogenic cell death (ICD) indicated by the increased expression of "danger signals", including HMGB1, CRT and ATP in 4T1 cells. Subsequently, the ICD derivatives-containing supernatant from HANPs-treated 4T1 cells activated macrophage and shifted the phenotype of the cells toward M1 type. Moreover, in a tumor-bearing mice model, HANPs and MPLA synergistically delayed tumor growth compared to PBS control, which was positively associated with the promoted macrophage polarization and ICD induction. Therefore, our findings demonstrated a potential platform to modulate the function of macrophages, and shed a new insight into the mechanism involving the immunomodulatory effect of HANPs for tumor therapy. Polarizing macrophage toward tumoricidal phenotype by harnessing Toll-like receptor (TLR) agonists has been proven effective for tumor immunotherapy. However, the immunomodulatory potency of TLR agonists is limited due to immune suppression or tolerance associated with TLR activation in immune cells. Herein, we introduced hydroxyapatite nanoparticles (HANPs) to MPLA, a TLR4 agonist. The results demonstrated that the addition of HANPs to MPLA promoted macrophage shift toward tumoricidal M1 phenotype, supported a "hot" tumor transformation, and delayed 4T1 tumor growth. Moreover, we found that HANPs elicited immunogenic cell death that produced "danger" signals from cancer cells thereby further facilitated macrophage polarization. This work is significant to direct the rational design of HANPs coupled with or without TLR agonists for tumor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Hydroxyapatite nanoparticles (HAp NPs) were synthesized with Muntingia calabura leaf extract as solvent and eggshell waste as a calcium source. The synthesized nanoparticles were irregular rod-like, as visualized by FESEM, while EDX and XPS studies confirmed the formation of hydroxyapatite. The synthesized HAp NPs were polycrystalline and highly thermostable as per XRD and TGA studies respectively. FTIR confirmed the stable coating of plant phytochemicals onto the HAp NPs. Congo red adsorption using HAp NPs nanoadsorbent was optimized by central composite design, wherein 89.96% of 33.18 mg/L dye was adsorbed in 137 min at 180 RPM. The adsorption process was in line with pseudo-second-order model and the Freundlich isotherm indicated chemical adsorption. The adsorption process was feasible, exothermic, and spontaneous as indicated by the thermodynamic studies. The adsorption capacity of HAp NPs stood at a maximum of 217 mg/g, indicating its superiority among other adsorbents reported earlier. It is evident from the convincing results that the HAp NPs synthesized in the present investigation may have a major role in developing novel adsorbents for dye removal out of wastewater streams.

The aim of the study was to fabricate and characterize composite macroporous hydrogels based on a hyaluronic acid/chitosan (Hyal/Ch) polyelectrolyte complex (PEC) loaded with homogeneously distributed hydroxyapatite nanoparticles (nHAp), and to evaluate them in vitro using mouse fibroblasts (L929), osteoblast-like cells (HOS) and human mesenchymal stromal cells (hMSC). Hydrogel morphology as a function of the hydroxyapatite nanoparticle content was studied using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The mean pore size in the Hyal/Ch hydrogel was 204 ± 25 μm. The entrapment of nHAp (1 and 5 wt. %) into the Hyal/Ch hydrogel led to a mean pore size decrease (94 ± 2 and 77 ± 9 μm, relatively). Swelling ratio and weight loss of the hydrogels in various aqueous media were found to increase with an enhancement of a medium ionic strength. Cell morphology and localization within the hydrogels was studied by CLSM. Cell viability depended upon the nHAp content and was evaluated by MTT-assay after 7 days of cultivation in the hydrogels. An increase of the hydroxyapatite nanoparticles loading in a range of 1–10 wt. % resulted in an enhancement of cell growth and proliferation for all hydrogels. Maximum cell viability was obtained in case of the Hyal/Ch/nHAp-10 sample (10 wt. % nHAp), while a minimal cell number was found for the Hyal/Ch/nHAp-1 hydrogel (1 wt. % nHAp). Thus, the proposed simple original technique and the design of PEC hydrogels could be promising for tissue engineering, in particular for bone tissue repair.

Nanocomposites based on thermoplastic polyurethane (TPU) and poly lactic acid (PLA) with different weight ratios of 10:90 and 30:70 were prepared by solution method. Hydroxyapatite nanoparticles (n-HA) were used to enhance the physical and mechanical properties of the alloys. To prepare the nanocomposites, the percentages of n-HA varied between 1% and 5%. Different tests were used to investigate the properties of these nanocomposites. Scanning electron microscopy (SEM) analysis, which was used to study the morphology of the blends, showed that there were rough morphologies in between materials, and the results of the mapping test showed that the dispersion of nanoparticles in the polymer matrix was almost good. TGA thermal degradation test showed that the presence of TPU to some extent can affect the thermal stability properties, and with the increase in this material, the thermal properties are strengthened. The crystalline behavior of the samples showed that the presence of TPU and n-HA nanoparticles had negative effects on the crystalline properties. The study of viscoelastic behaviors showed that the presence of TPU enhances the viscous behavior in the sample and decreases the glass transition temperature, while the presence of nanoparticles increases the elastic properties and glass transition temperature. Tensile test showed that the presence of n-HA has a greater effect on the mechanical properties. Dynamic contact angle analysis using water and dimethylformamide (DMF) solvent showed that the existing TPU and n-HA led to major changes in the interaction surface of scaffolds. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis showed that increasing the amounts of TPU and HA increases cell viability. SEM cell interactions analysis showed that the surfaces of PLA90TPU10H5 and PLA70TPU30H5 samples are very good for the preparation of bone tissue scaffolds. Our findings indicated that the addition of n-HA into PLA/TPU blends could impart new features to the PLA matrix as a promising candidate for bone, cartilage, and tendon tissue engineering.

Multiphasic scaffolds that combine different architectural, physical, and biological properties are the best option for the regeneration of complex tissues such as the periodontium. Current developed scaffolds generally lack architectural accuracy and rely on multistep manufacturing, which is difficult to implement for clinical applications. In this context, direct-writing electrospinning (DWE) represents a promising and rapid technique for developing thin 3D scaffolds with controlled architecture. The current study aimed to elaborate a biphasic scaffold using DWE based on two polycaprolactone solutions with interesting properties for bone and cement regeneration. One of the two scaffold parts contained hydroxyapatite nanoparticles (HAP) and the other contained the cementum protein 1 (CEMP1). After morphological characterizations, the elaborated scaffolds were assessed regarding periodontal ligament (PDL) cells in terms of cell proliferation, colonization, and mineralization ability. The results demonstrated that both HAP- and CEMP1-functionalized scaffolds were colonized by PDL cells and enhanced mineralization ability compared to unfunctionalized scaffolds, as revealed by alizarin red staining and OPN protein fluorescent expression. Taken together, the current data highlighted the potential of functional and organized scaffolds to stimulate bone and cementum regeneration. Moreover, DWE could be used to develop smart scaffolds with the ability to spatially control cellular orientation with suitable cellular activity at the micrometer scale, thereby enhancing periodontal and other complex tissue regeneration. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during Kharif 2021 in farmer's field at Halavarthy village of Davanagere district, Karnataka, which comes under Central Dry Zone of Karnataka (Zone 4), using RCBD with eleven treatments and three replications to evaluate the impact of three different nano phosphorus fertilizers on the productivity of maize. Treatments included T1: Absolute control, T2: 100 per cent recommended package of practice (RPP), T3 to T5: 75 per cent RDP (75% recommended dose of P) through SSP + 5 per cent RDP through NP1(hydroxyapatite nano fertilizer), NP2 (nano rock phosphate) and NP3 (hydroxyapatite nanoparticles coated with CMC), T6 to T8: 75 per cent RDP + 1 per cent RDP through foliar spray of NP1, NP2 and NP3, T9 to T11: 75 per cent RDP + 5 per cent RDP through soil application of NP1, NP2 and NP3 and 1 per cent RDP through foliar spray of NP1, NP2 and NP3, respectively. Results revealed that application of phosphorus in nano form had significant effect on growth and yield of maize. Treatment with 75 per cent RDP through SSP + 5 per cent RDP through soil application of NP1 + 1 per cent RDP through foliar spray of NP1 recorded significantly higher plant height, number of leaves plant-1, chlorophyll content, dry matter accumulation, cob length (19.01 cm), number of rows cob-1 (16.27), number of kernels row-1 (35.27), test weight (33.20 g), stover yield (82.23 q ha-1) and kernel yield (73.59 q ha-1) over absolute control and were better when compared to T2 (100 % RPP). [ABSTRACT FROM AUTHOR]

Intelligent packaging with a pH indicator is a protective measure that can assure the food quality at the point of delivery or usage. This research targets to develop eggshell membrane gelatin-based hydroxyapatite (HAP) nanocomposite edible film incorporated with anthocyanin extracted from Jambolão (Syzygium cumini). The HAP nanoparticles were synthesized from eggshells, the size (< 100 nm) and morphology were confirmed by Dynamic light scattering (DLS), Scanning Electron Microscope (SEM), and Transmission Electron Microscope (TEM). Eggshell gelatin film, eggshell gelatin film reinforced with HAP (Gel-HAP), and anthocyanin incorporated eggshell gelatin film reinforced with HAP (Gel-HAP-ACN) were prepared. The physicochemical, optical, and surface properties of the nanocomposite films were evaluated. Gel-HAP-ACN film had excellent light barrier characteristics than Gel-HAP and Gel films. The Gel-HAP-ACN film had enhanced antioxidant (57.71%) property than the gelatin film and also had antibacterial action against Salmonella typhi, Escherichia coli and Staphylococcus aureus. Hence, this report suggests Gel-HAP-ACN film for food packaging to assure the safety of the food. [ABSTRACT FROM AUTHOR]

The deficiency of nutrients during the early plant growth stages diminishes plant development, leading ultimately to lower crop yields. In this context, nanotechnology has been used to develop advanced seed coatings with sustainable and precise release properties to deliver supplements to the plant effectively. Zinc-doped hydroxyapatite-urea nanoparticles were synthesized and incorporated into a seed coating. This system enhanced plant growth, yield and root-shoot nutrient content in Zea mays seeds. The nanohybrid is futuristic as a macro-micro plant nutrient delivery agent and opens up new opportunities to explore the suitability of metal-doped hydroxyapatite nanoparticles in agriculture. [ABSTRACT FROM AUTHOR]

Paper aging and protection processes play an essential function in the preservation of library collections and archives. In this study, some physical-mechanical properties of paper samples from XXth century books (private collections), such as pH acidity, tensile strength, and modulus of elasticity, as well as optical properties, such as absolute change in yellowness, were examined before and after treating them with hydroxyapatite nanoparticles (HAp). Accelerated light aging was also evaluated and discussed. The treatment with HAp nanoparticles increased the paper’s pH to slightly alkaline values (approximately pH 8). Washing and treating the paper improved its mechanical properties compared to untreated paper; the tear length increased by 35% and the modulus of elasticity increased by 56%. That the treated and aged samples are more elastic than the original samples demonstrates that HAp nanoparticles consolidated the cellulose fibers. Additionally, particle morphology, size, composition and size distribution were assessed via image analysis using scanning electron microscopy (SEM-EDX), atomic force microscopy (AFM), and the ImageJ processing program.

Hongfeng Wu,1,2 Shuo Liu,1,2 Siyu Chen,1,2 Yuchen Hua,1,2 Xiangfeng Li,1,2 Qin Zeng,1– 3 Yong Zhou,4 Xiao Yang,1,2 Xiangdong Zhu,1,2 Chongqi Tu,4 Xingdong Zhang1– 3 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China; 2College of Biomedical Engineering, Sichuan University, Chengdu, 610064, People’s Republic of China; 3NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, 610064, People’s Republic of China; 4Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Qin Zeng; Xiangdong Zhu, National Engineering Research Center for Biomaterials, Sichuan University, NO. 29 Wangjiang Road, Chengdu, 610064, People’s Republic of China, Email qzeng8156@scu.edu.cn; zhu_xd1973@scu.edu.cnBackground: In recent years, using hydroxyapatite nanoparticles (HANPs) for tumor therapy attracted increasing attention because HANPs were found to selectively suppress the growth of tumor cells but exhibit ignorable toxicity to normal cells.Purpose: This study aimed to investigate the capacities of HANPs with different morphologies and particle sizes against two kinds of osteosarcoma (OS) cells, human OS 143B cells and rat OS UMR106 cells.Methods: Six kinds of HANPs with different morphologies and particle sizes were prepared by wet chemical method. Then, the antitumor effect of these nanoparticles was characterized by means of in vitro cell experiments and in vivo tumor-bearing mice model. The underlying antitumor mechanism involving mitochondrial apoptosis was also investigated by analysis of intracellular calcium, expression of apoptosis-related genes, reactive oxygen species (ROS), and the endocytosis efficiency of the particles in tumor cells.Results: Both in vitro cell experiments and in vivo mice model evaluation revealed the anti-OS performance of HANPs depended on the concentration, morphology, and particle size of the nanoparticles, as well as the OS cell lines. Among the six HANPs, rod-like HANPs (R-HANPs) showed the best inhibitory activity on 143B cells, while needle-like HANPs (N-HANPs) inhibited the growth of UMR106 cells most efficiently. We further demonstrated that HANPs induced mitochondrial apoptosis by selectively raising intracellular Ca2+ and the gene expression levels of mitochondrial apoptosis-related molecules, and depolarizing mitochondrial membrane potential in tumor cells but not in MC3T3-E1, a mouse pre-osteoblast line. Additionally, the anti-OS activity of HANPs also linked with the endocytosis efficiency of the particles in the tumor cells, and their ability to drive oxidative damage and immunogenic cell death (ICD).Conclusion: The current study provides an effective strategy for OS therapy where the effectiveness was associated with the particle morphology and cell line.Keywords: hydroxyapatite nanoparticles, osteosarcoma, material features, cell line, mitochondrial apoptosis

Malignant bone tumors can inflict significant damage to affected bones, leaving patients to contend with issues like residual tumor cells, bone defects, and bacterial infections post-surgery. However, hydroxyapatite nanoparticles (nHAp), the principal inorganic constituent of natural bone, possess numerous advantages such as high biocompatibility, bone conduction ability, and a large surface area. Moreover, nHAp’s nanoscale particle size enables it to impede the growth of various tumor cells via diverse pathways. This article presents a comprehensive review of relevant literature spanning the past 2 decades concerning nHAp and bone tumors. The primary goal is to explore the mechanisms responsible for nHAp’s ability to hinder tumor initiation and progression, as well as to investigate the potential of integrating other drugs and components for bone tumor diagnosis and treatment. Lastly, the article discusses future prospects for the development of hydroxyapatite materials as a promising modality for tumor therapy.

Dental caries is one of the most common human diseases which can occur in both primary and permanent dentitions throughout the life of an individual. Hydroxyapatite is the major inorganic component of human teeth, consequently, nanosized hydroxyapatite (nHAP) has recently attracted researchers' attention due to its unique properties and potential for caries management. This article provides a contemporary review of the potential beneficial effects of nHAP on caries lesions demonstrated in in vitro studies. Data showed that nHAP has potential to promote mineralization in initial caries, by being incorporated into the porous tooth structure, which resulted from the caries process, and subsequently increased mineral content and hardness. Notably, it is the particle size of nHAP which plays an important role in the mineralization process. Antimicrobial effects of nHAP can also be achieved by metal substitution in nHAP. Dual action property (mineralizing and antimicrobial) and enhanced chemical stability and bioactivity of nHAP can potentially be obtained using metal-substituted fluorhydroxyapatite nanoparticles. This provides a promising synergistic strategy which should be explored in further clinical research to enable the development of dental therapeutics for use in the treatment and management of caries. [ABSTRACT FROM AUTHOR]

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC50 value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca2+ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca2+ ions causes cells to undergo apoptosis. Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half. [ABSTRACT FROM AUTHOR]

The development of natural polymer-based scaffolds with excellent biocompatibility, antibacterial activity, and blood compatibility, able to facilitate full-thickness skin wound healing, remains challenging. In this study, we have developed three chitosan (CS)-based porous scaffolds, including CS, CS/CNT (carbon nanotubes) and CS/CNT/HA (nano-hydroxyapatite, n-HA) using a freeze-drying method. All three scaffolds have a high swelling ratio, excellent antibacterial activity, outstanding cytocompatibility and blood compatibility in vitro. The introduction of CNTs exhibited an obvious increase in mechanical properties and exerts excellent photothermal response, which displays excellent healing performance as a wound dressing in mouse full-thickness skin wound model when compared to CS scaffolds. CS/CNT/HA composite scaffolds present the strongest ability to promote full-thickness cutaneous wound closure and skin regeneration, which might be ascribed to the synergistic effect of photothermal response from CNT and excellent bioactivity from n-HA. Overall, the present study indicated that CNT and n-HA can be engineered as effective constituents in wound dressings to facilitate full-thickness skin regeneration. [ABSTRACT FROM AUTHOR]

Poly (glycerol sebacate citrate) (PGSC) has potential applications in tissue engineering due to its biodegradability and suitable elasticity. However, its applications are restricted owing to its acidity and high degradation rate. In this study, a new bio-nanocomposite based on PGSC has been synthesized by incorporating chitosan (CS) and various concentrations of hydroxyapatite nanoparticles (n-HA). It is assumed that the basicity of a CS and hydroxyl groups of n-HA will reduce the acidity of PGSC and control the rate of degradation. Also, the biocompatibility of n-HA and inherent hydrophilicity of CS can improve cell adhesion and proliferation of PGSC-based scaffolds. FTIR, XRD, FESEM, and EDX tests confirmed the synthesis of these nanocomposites and the interaction between each of the components. The results of the DMTA test also indicated the elastic behavior of the samples embedded with n-HA. The hydrophilicity assay demonstrated that the water contact angle of the scaffolds decreased as the concentration of n-HA augmented, and it reached the value of 44 ± 0.9° for nanocomposite containing 5 wt.% n-HA. The degradation rate of all PGSC nanocomposites was reduced due to the anionic groups of n-HA and CS. TGA assay indicated that the incorporation of n-HA led to the enhancement of scaffolds' thermal stability. Furthermore, the synergistic effect of CS and n-HA on the enhancement of protein adsorption and cell proliferation was confirmed through protein adhesion and MTT assay, respectively. Consequently, the addition of n-HA and CS perform the new bio-nanocomposites scaffolds based on PGSC with sufficient hydrophilicity, flexibility, and thermal stability in tissue engineering applications. Potential applications of PGSC in tissue engineering due to its elasticity properties Suitable hydrophilicity of PGSC in the presence of CS and hydroxyapatite Synergistic effect of CS and n-HA on the control of degradation rate Significant impact of n-HA on cell proliferation and cell adhesion properties [ABSTRACT FROM AUTHOR]

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D-printed scaffolds with ideal mechanical and biological properties remains an unattained challenge. In the present work, a new approach to produce synthetic bone grafts that mimic complex bone structure is explored. For the first time, three scaffolds of various composition, namely polycaprolactone (PCL), PCL/hydroxyapatite nanoparticles (HANp) and PCL/HANp/diacrylate poly(ethylene glycol) (PEGDA), were manufactured by extrusion. Following the production and characterisation of the scaffolds, an in vitro evaluation was carried out using human dental pulp stem/stromal cells (hDPSCs). Through the findings, it was possible to conclude that, in all groups, the scaffolds were successfully produced presenting networks of interconnected channels, adequate porosity for migration and proliferation of osteoblasts (approximately 50%). Furthermore, according to the in vitro analysis, all groups were considered non-cytotoxic in contact with the cells. Nevertheless, the group with PEGDA revealed hydrophilic properties (15.15° ± 4.06) and adequate mechanical performance (10.41 MPa ± 0.934) and demonstrated significantly higher cell viability than the other groups analysed. The scaffolds with PEGDA suggested an increase in cell adhesion and proliferation, thus are more appropriate for bone regeneration. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes. [ABSTRACT FROM AUTHOR]

The aim of the study was to fabricate and characterize composite macroporous hydrogels based on a hyaluronic acid/chitosan (Hyal/Ch) polyelectrolyte complex (PEC) loaded with homogeneously distributed hydroxyapatite nanoparticles (nHAp), and to evaluate them in vitro using mouse fibroblasts (L929), osteoblast-like cells (HOS) and human mesenchymal stromal cells (hMSC). Hydrogel morphology as a function of the hydroxyapatite nanoparticle content was studied using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The mean pore size in the Hyal/Ch hydrogel was 204 ± 25 μm. The entrapment of nHAp (1 and 5 wt. %) into the Hyal/Ch hydrogel led to a mean pore size decrease (94 ± 2 and 77 ± 9 μm, relatively). Swelling ratio and weight loss of the hydrogels in various aqueous media were found to increase with an enhancement of a medium ionic strength. Cell morphology and localization within the hydrogels was studied by CLSM. Cell viability depended upon the nHAp content and was evaluated by MTT-assay after 7 days of cultivation in the hydrogels. An increase of the hydroxyapatite nanoparticles loading in a range of 1–10 wt. % resulted in an enhancement of cell growth and proliferation for all hydrogels. Maximum cell viability was obtained in case of the Hyal/Ch/nHAp-10 sample (10 wt. % nHAp), while a minimal cell number was found for the Hyal/Ch/nHAp-1 hydrogel (1 wt. % nHAp). Thus, the proposed simple original technique and the design of PEC hydrogels could be promising for tissue engineering, in particular for bone tissue repair. [ABSTRACT FROM AUTHOR]

Background: Hydroxyapatite nanoparticles (nHAp) have excellent properties, such as biocompatibility and osteoconductivity, which are critical for bone reconstruction. However, they remain inactive against pathogenic bacteria that can grow in defected bone tissue, and their use in some patients may result in some undesirable inflammatory reactions. Gallic acid (GA) is known for its specific anti-inflammatory and antibacterial properties. Coupling these characteristics with nHAp is of great interest. Methods: The present study investigated the preparation of nHAp in the presence of various proportions of GA (0, 0.6, 2.5, and 5 mMol) using the neutralization method at room temperature. The effect of GA on the crystallinity, chemical composition, and surface specific area (SSA) of the prepared nHAp-GA composites was also studied. Results: X-ray diffraction and Brunauer-Emmett-Teller (BET) analysis revealed that the precipitation of nHAp in the presence of a low fraction of GA induced the formation of nHAp with low crystallinity and high SSA (142 m2/g), while GA at high concentration limited nHAp growth and favored the ACP formation with low SSA (32 m2/g). X-ray photoelectron spectroscopy (XPS) indicated that GA is adsorbed on the nHAp surface and controlled its growth. Conclusion: Overall, the prepared nHAp/Ga composites presented chemical and structural characteristics close to those of natural bone that make them a good candidate for bone tissue regeneration.

The conversion of the fish and shrimp wastes to produce value-added products brings economic benefits and reduces the risk of environmental pollution. This study presents a facile method for preparing nano-hydroxyapatite/chitosan biocomposites (nHCB) for wastewater treatment and bacterial immobilization. It is a novelty that hydroxyapatite nanoparticles (nHA) and chitosan (CTS) were recovered from fishbone and shrimp shell sources. The prepared nHCBs showed a high porosity, and nHA particles were well distributed in the CTS matrix. Due to these unique properties as an adsorbent for removing dyes and Cu(II) ions from wastewater, nHCBs exhibited rapid adsorption, high capacity, and easy separation for cyclic use. The maximum sorption capacity were 44.05 mg/g (methylene orange), 84.89 mg/g (methylene blue), and 236.97 mg/g (Cu(II) ions). The findings suggest a great potential fabrication of low-cost bio-composites and their application for wastewater treatment.

For many years, the primary focus has been on finding effective treatments for Alzheimer’s disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15–20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity. [ABSTRACT FROM AUTHOR]

In the present study, a novel chitosan-functionalized graphene oxide decorated with glycidyl methacrylate (GO–CS–GMA) was synthesized and combined with nanohydroxyapatite particles (nHAp) to produce a novel hybrid synthetic natural material as a reinforcing phase for dental and biomedical purposes. In this process, the graphene oxide converted to GO–COCl, then reacted with chitosan (CS) to prepare GO–CS and final reaction of GO–CS with glycidyl methacrylate (GMA) gave methacrylate functionalized GO–CS–GMA. In another process, an alkyl bromide derivative of nanohydroxyapatite (nHAp-Br, radical initiator) was made from reaction of nHAP with 2-bromoisobutyryl bromide. Finally, atom transfer radical polymerization (ATRP) was used to the grafting of GO–CS–GMA onto nHAp surface to give nanohybrid compounds that were utilized in the nanocomposite formulation. The structure, thermal stability, and mechanical properties of the nanocomposites were investigated by FTIR, XRD, CHN, FE-SEM, and TGA. The thermal stability of the final composite was higher than its precursor nHAp and GO–CS–GMA. A synergistic effect of graphene oxide, chitosan, and glycidyl methacrylate on reinforcing hydroxyapatite has been observed. The resulting nanocomposite revealed around 56% and 20% increases in compressive and flexural strength, respectively, in comparison with hydroxyapatite. In addition, both compressive and flexural strengths of new composites were improved in comparison with the conventional composites which are made from barium glass fillers. Cellular studies using human alveolar basal epithelial cells (A549 cell line) suggest that remarkable biocompatibility is shown by nHAp-g-GO–CS–GMA, which makes it an encouraging material for biomedical applications. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAp) is a naturally occurring calcium phosphate mineral predominantly used for its biocompatibility in a number of areas such as bone grafting, prosthesis coating in dentistry, and targeted drug delivery. Since the nano form of HAp (nHAp) has gained popularity attributed to a re-mineralizing effect in dental repair procedures, concerns have been raised over safety and biocompatibility of these nanoparticles (NP). This study, therefore, aimed to (1) investigate mechanisms of potential genotoxicity and enhanced generation of reactive oxygen species (ROS) initiated by bulk and nano forms of HAp and (2) test in vivo whether resveratrol, a type of natural phenol, might mitigate the extent of potential DNA damage. The size of nHAp was determined to be 192.13 ± 9.91 nm after dispersion using transmission electron microscopy (TEM). Drosophila melanogaster was employed as a model organism to determine the genotoxic potential and adverse effects of HAp by use of (comet assay), mutagenic and recombinogenic activity (wing spot test), and ROS-mediated damage. Drosophila wing-spot tests demonstrated that exposure to nontoxic bulk and nHAp concentrations (1, 2.5, 5 or 10 mM) produced no significant recombination effects or mutagenicity. However, bulk and nHAp at certain doses (2.5, 5 or 10 mM) induced genotoxicity in hemocytes and enhanced ROS production. Resveratrol was found to ameliorate the genotoxic effects induced by bulk HAp and nHAp in comet assay. Data demonstrate that treatment with nano and bulk Hap-induced DNA damage and increased ROS generation D. melanogaster which was alleviated by treatment with resveratrol. [ABSTRACT FROM AUTHOR]

The enthesis is an extremely specific region, localized at the tendon–bone interface (TBI) and made of a hybrid connection of fibrocartilage with minerals. The direct type of enthesis tissue is commonly subjected to full laceration, due to the stiffness gradient between the soft tissues and hard bone, and this often reoccurs after surgical reconstruction. For this purpose, the present work aimed to design and develop a tubular scaffold based on pullulan (PU) and chitosan (CH) and intended to enhance enthesis repair. The scaffold was designed with a topographical gradient of nanofibers, from random to aligned, and hydroxyapatite (HAP) nanoparticles along the tubular length. In particular, one part of the tubular scaffold was characterized by a structure similar to bone hard tissue, with a random mineralized fiber arrangement; while the other part was characterized by aligned fibers, without HAP doping. The tubular shape of the scaffold was also designed to be extemporarily loaded with chondroitin sulfate (CS), a glycosaminoglycan effective in wound healing, before the surgery. Micro CT analysis revealed that the scaffold was characterized by a continuous gradient, without interruptions from one end to the other. The gradient of the fiber arrangement was observed using SEM analysis, and it was still possible to observe the gradient when the scaffold had been hydrated for 6 days. In vitro studies demonstrated that human adipose stem cells (hASC) were able to grow and differentiate onto the scaffold, expressing the typical ECM production for tendon in the aligned zone, or bone tissue in the random mineralized part. CS resulted in a synergistic effect, favoring cell adhesion/proliferation on the scaffold surface. These results suggest that this tubular scaffold loaded with CS could be a powerful tool to support enthesis repair upon surgery. [ABSTRACT FROM AUTHOR]

The potency of Toll-like receptor 9 (TLR9) agonist to drive innate immune response was limited due to immune suppression or tolerance during TLR9 signaling activation in immune cells. Herein we addressed this problem by introducing hydroxyapatite nanoparticles (HANPs) to CpG ODN (CpG), a TLR9 agonist. The study revealed that HANPs concentration and duration-dependently reprogramed the immune response by enhancing the secretion of immunostimulatory cytokines (tumor necrosis factor α (TNFα) or IL-6) while reducing the production of immunosuppressive cytokine (IL-10) in macrophages in response to CpG. Next, the enhanced immune response benefited from increased intracellular Ca2+ in macrophage by the addition of HANPs. Further, we found exposure to HANPs impacted the mitochondrial function of macrophages in support of the synthesis of adenosine triphosphate (ATP), the production of nicotinamide adenine dinucleotide (NAD), and reactive oxygen species (ROS) in the presence or absence of CpG. In vaccinated mice model, only one vaccination with a mixture of CpG, HANPs, and OVA, a model antigen, allowed the development of a long-lasting balanced humoral immunity in mice without any histopathological change in the local injection site. Therefore, this study revealed that HANPs could modulate the intracellular calcium level, mitochondrial function, and immune response in immune cells, and suggested a potential combination adjuvant of HANPs and TLR9 agonist for vaccine development. [ABSTRACT FROM AUTHOR]

Paper aging and protection processes play an essential function in the preservation of library collections and archives. In this study, some physical-mechanical properties of paper samples from XXth century books (private collections), such as pH acidity, tensile strength, and modulus of elasticity, as well as optical properties, such as absolute change in yellowness, were examined before and after treating them with hydroxyapatite nanoparticles (HAp). Accelerated light aging was also evaluated and discussed. The treatment with HAp nanoparticles increased the paper's pH to slightly alkaline values (approximately pH 8). Washing and treating the paper improved its mechanical properties compared to untreated paper; the tear length increased by 35% and the modulus of elasticity increased by 56%. That the treated and aged samples are more elastic than the original samples demonstrates that HAp nanoparticles consolidated the cellulose fibers. Additionally, particle morphology, size, composition and size distribution were assessed via image analysis using scanning electron microscopy (SEM-EDX), atomic force microscopy (AFM), and the ImageJ processing program. [ABSTRACT FROM AUTHOR]

Methods for the synthesis and characterization of well‐dispersed nanostructured materials are widely explored for potential applications in various fields. Several challenges in synthesizing nanoparticles (NPs) with controlled morphology, narrow size distribution, and optimum stability are tested but the fundamental understanding of the growth of NP crystal structure leading to various morphologies still needs to be addressed. This study attempts to understand the role of the synthesis environment, i.e., solvents, stabilizing agents, and the surfactant concentration, that controls the crystal growth of the synthesized biocompatible hydroxyapatite nanoparticles resulting in different shapes and sizes. The lattice parameters, space group, interplanar spacing, and unit cell dimensions are calculated using the experimentally obtained powder diffraction patterns for the various NPs. Atoms are placed at random sites in the unit cell based on the collected crystallographic information, and a final atomic arrangement and subsequent morphological evolution are arrived at via local and global optimization. [ABSTRACT FROM AUTHOR]

We successfully synthesized folic acid (FA) immobilized hydroxyapatite (HA) nanoparticles without using a mediative reagent (e.g., silane coupling agent), and the immobilization states were evaluated and discussed. The HA nanoparticles with higher biocompatibility have two different planes, namely, c - and m -planes. These plane surfaces are rich in phosphate groups (P-site) and Ca 2+ ions (C-site), respectively. We suggested that during the synthesis of the HA nanoparticles, the P-site substitution and C-site coordination with the addition of organic molecules containing -COO - ions can occur. Thus, it is possible to simultaneously immobilize two molecules to one HA nanoparticle. In this study, we successfully synthesized FA-immobilized HA nanoparticles by P-site substitution and C-site coordination reactions, which were named as substitution type and coordination type. In the substitution type, when FA was reacted with HA during the nucleation stage, the PO 4 3- ions of HA decreased as the FA ratio of coverage surface area increased, and the crystalline phase was changed significantly from the Ca deficient HA to the carbonated HA phase. Accordingly, it was indicated that FA was immobilized on HA by the P-site substitution. In the coordination type, since FA was reacted with HA after the completion of crystal growth, the crystalline phase was changed slightly as the FA ratio of coverage surface area increased, indicating that FA was immobilized on HA by the C-site coordination. From the above, we controlled the FA immobilization states on the HA nanoparticles by the P-site substitution and the C-site coordination through the FA addition timing in the synthesis. Since the -COO - ions in FA could be selectively substituted with the P-site in HA, it is possible to directly coordinate the foreign organic molecules to the Ca 2+ ions in HA. Therefore, the immobilization technique of this study is expected to achieve two different drug molecules with diagnosis and therapy functions (i.e., theranostics) on one nanoparticle.

Hydroxyapatite nanoparticles (nHA) have gained attention as potential intracellular drug delivery vehicles due to their high binding affinity for various biomolecules and pH-dependent solubility. Yet, the dependence of nHA cytocompatibility on their physicochemical properties remains unclear since numerous studies have revealed starkly contrasting results. These discrepancies may be attributed to differences in size, shape, crystallinity, and aggregation state of nHA, which complicates fundamental understanding of the factors driving nHA cytotoxicity. Here, we hypothesize that nHA cytotoxicity is primarily driven by intracellular calcium levels following the internalization of nHA nanoparticles. By investigating the cytotoxicity of spherical nHA with different crystallinity and dispersity, we find that both lower crystallinity and increased agglomeration of nHA raise cytotoxicity, with nanoparticle agglomeration being the more dominant factor. We show that the internalization of nHA enhances intracellular calcium levels and increases the production of reactive oxygen species (ROS). However, only subtle changes in intracellular calcium are observed, and their physiological relevance remains to be confirmed. In conclusion, we show that nHA agglomeration enhances ROS production and the associated cytotoxicity. These findings provide important guidelines for the future design of nHA-containing formulations for biomedical applications, implying that nHA crystallinity and especially agglomeration should be carefully controlled to optimize biocompatibility and therapeutic efficacy.