Hydroxyapatite Nanoparticles Research Articles

Synthesis and characterization of Alginate-Ag-attapulgite with different ratios of hydroxyapatite nanoparticles

Synthesis and characterization of Alginate-Ag-attapulgite with different ratios of hydroxyapatite nanoparticles

Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair.

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.

Immobilization of cationic dye on photoluminescent hydroxyapatite particles through a citric acid bonding layer

Promotion of the immobilization of cationic porphyrin on Eu(iii) ion-doped hydroxyapatite nanoparticles through citric acid as the bonding layer was achieved.

Effect of Hydroxyapatite Nanoparticles Addition to Resin Modified Glass Ionomer Cement on Degree of Convergence and Fluoride Release

Effect of Hydroxyapatite Nanoparticles Addition to Resin Modified Glass Ionomer Cement on Degree of Convergence and Fluoride Release

Iodine-substituted hydroxyapatite nanoparticles and activation of derived ceramics for range verification in proton therapy.

Osteosarcoma is a radioresistant cancer, and proton therapy is a promising radiation alternative for treating cancer with the advantage of a high dose concentration in the tumor area. In this work, we propose the use of iodine-substituted hydroxyapatite (IHAP) nanomaterials to use iodine (127I) as a proton radiation tracer, providing access to range verification studies in mineralized tissues. For this purpose, the nanomaterials were synthesized at four iodine concentrations via hydrothermal synthesis. The materials were characterized via different microstructural techniques to identify an optimal high iodine concentration and pure apatite phase nanomaterial. Finally, such pure IHAP powders were shaped and irradiated with proton beams of 6 and 10 MeV, and their activation was demonstrated through subsequent decay analysis. The materials could be integrated into phantom structures for the verification of doses and ranges of protons prior to animal testing and clinical proton therapy treatments of tumors located deep under combined soft and calcified tissues.

Antibacterial Activity of Laser Ablated Gold and Hydroxyapatite Nanoparticles Conjugated Cefuroxime against Staphylococcus saprophyticus

Antibacterial Activity of Laser Ablated Gold and Hydroxyapatite Nanoparticles Conjugated Cefuroxime against Staphylococcus saprophyticus

Physical and mechanical properties assessment of glass ionomer cements modified with TiO2 and Mg-doped hydroxyapatite nanoparticles.

High viscosity glass ionomer cements (GICs) are widely used in various clinical applications, being particularly effective in atraumatic restorative treatment (ART) due to the synergistic interaction between the material and the technique. However, the inadequate mechanical properties of GICs raise concerns regarding the predictability and longevity of these restorations in areas exposed to occlusal stress. Various modifications of the powder components have been proposed to improve the mechanical strength of GICs to withstand occlusal loading during mastication. In this in vitro study, we investigated whether the nanoparticles (NPs) added to commercially available GICs could fulfill this requirement, which would likely broaden the spectrum of their potential clinical applications. Two commercially available GIC powders (Fuji IX and Ketac Molar), modified by the addition of 5 wt.% TiO2, MgHAp100 or MgHAp1000 NPs, were incorporated into the corresponding liquid in an appropriate ratio, and the mixed cements were evaluated in terms of fracture toughness, flexural strength, Vickers microhardness and rheological tests and compared with the original material. Fuji IX containing 5 wt.% MgHAp100 NPs had lower flexural strength, while Ketac Molar with 5 wt.% TiO2 NPs showed increased fracture toughness. Vickers microhardness increased in Fuji IX following the addition of 5 wt.% TiO2 and MgHAp100 but decreased in Ketac Molar comprising 5 wt.% MgHAp100 (p < 0.05). Achieving a predictable bond between NPs and cement matrix, as well as ensuring a uniform distribution of the NPs within the cement, are critical prerequisites for enhancing the mechanical performance of the original cement.

Preparation of hydroxyapatite nanoparticle-hyaluronic acid hybrid membranes through citric acid molecular mediation

Citric acid (Cit)-coordinated hydroxyapatite nanoparticles (NPs) were successfully nanohybridized with hyaluronic acid (HYA) to form transparent membranes, where hydrogen bonds were formed between the NPs and HYA through Cit mediation.

Synthesis of nano-hydroxyapatite using emulsion, pyrolysis, combustion, and sonochemical methods and biogenic sources: a review.

Hydroxyapatite (HAp) is comparable to materials in bone because its chemical components are similar to those contained in animal bone, and thus, its bioactive and biocompatible properties are similar. There are applications for HAp and relevant calcium phosphate in the medical and industrial sectors, and due to the rising demand for HAp nanoparticles, considerable work has been performed to develop a variety of synthetic pathways that incorporate scientifically and practically novel aspects. Numerous studies have been conducted to examine how changes in reaction parameters will successfully influence crucial HAp features. HAp can also be synthesized from biogenic sources such as HAp-rich fish scales or animal bones as an alternative to chemical precursors. Various preparation techniques produce crystals with varying sizes, but it has been found that nano-sized HAp exhibits a greater number of bioactive properties as compared to micron-sized HAp. Rather than considering conventional methods, this review focuses on alternative approaches such as emulsion, pyrolysis, combustion, and sonochemical methods along with waste bio-sources (biogenic sources) to obtain HAp. We summarize the currently accessible information pertaining to each synthesis process, while also focusing on their benefits and drawbacks.

Toward chronopharmaceutical drug delivery patches and biomaterial coatings for the facilitation of wound healing

Implantation of a biomaterial entails a form of injury where the integration of the implant into the host tissue greatly depends on the proper healing of the wound. Wound healing, itself, consists of a number of physiological processes, each occurring within a characteristic time window. A composite, multilayered polymeric drug delivery carrier for adhesion to the wound site and its supply with molecules released at precise time windows at which the stages in the healing process that they target occur is conceptualized here. We also present a simplified version of one such multilayered composite fabricated by a combination of solvent casting and dip coating, comprising the base poly(ε-caprolactone) layer reinforced with hydroxyapatite nanoparticles, poly(glutamic acid) mesolayer and poly-l-lysine surface layer, each loaded with specific small molecules and released at moderately distinct timescales, partially matching the chronology of wound healing. To that end, the base layer proved suitable for the delivery of an anti-inflammatory molecule or an angiogenic agent, the mesolayer appeared appropriate for the delivery of an epithelialization promoter or a granulation factor, and the adhesive surface layer interfacing directly with the site of injury showed promise as a carrier of a vasodilator. The drug release mechanisms were diffusion-driven, suggesting that the drug/carrier interaction is a key determinant of the release kinetics, as important as the nature of the polymer and its hydrolytic degradation rate in the aqueous medium. Morphological and phase composition analyses were performed, along with the cell compatibility ones, demonstrating solid adhesion and proliferation of both transformed and primary fibroblasts on both surfaces of the composite films. The design of the multilayered composite drug delivery carriers presented here is prospective, but requires further upgrades to achieve the ideal of a perfect timing of the sequential drug release kinetics and a perfect resonance with the physiological processes defining the chronology of wound healing.

Bio-inspired liquid crystal gel induction via nano-hydroxyapatite mesogens: Viscoelastic and hemostasis regulation under bone remodeling pH and temperature control

In this work, a liquid crystal mesophase as a potential bone-repairing booster has been induced from a polyacrylic acid (PAAc) gel loaded with synthetic hydroxyapatite nanoparticles (nHA) under physiological conditions of pH and temperature that resemble the early stages of bone formation. Dynamic processes at the microscale in biological systems require a material capable of behaving following a specific order and fluency. Besides, they must fulfill conditions such as biocompatibility and good mechanical properties. Our study aimed to obtain new data about the safety, hemostasis, biocompatibility (activated partial thromboplastin time (APTT) test, prothrombin time (PT) test, lactate dehydrogenase (LDH) test, red blood cell morphology observation, hemolysis percentage) and physicochemical/mechanical behavior (Attenuated Total Reflection (ATR), Infrared spectroscopy and rheological assays) of nanoparticles, and materials built with them. Both systems have shown biocompatibility with red blood cells and adequate flow properties, demonstrating promising qualities for applicability. The formation of lyotropic liquid crystals at physiological conditions was evaluated with crossed polaroids microscope with a temperature control plate. The formation of these structures under bone remodeling conditions shows the potential application of PAAc-nHA materials. In literature, the study of materials applied as bone fillers is mainly focused on mechanical and osteoblasts compatibility assays. However, the hematological effect, consequences on the coagulation cascade, the integrity of cell membranes, and hemolysis percentage have not been addressed thoroughly. The strength of our work is focused on considering these aspects when tridimensional arrangements essential for bone formation are formed.

Development and characterization of antibacterial 3D porous hydroxyapatite-gelatin-PVA scaffolds containing zinc oxide nanoparticles

There is still a need to develop hydroxyapatite (HAp)/gelatin-based porous scaffolds to provide a hybrid system with structural and biochemical properties equivalent to those of bone. Here, we fabricated and characterized 3D hybrid scaffolds composed of HAp nanoparticles synthesized in situ in gelatin and PVA solutions and loaded with combustionally synthesized (10 wt%) zinc oxide nanoparticles (ZnO NPs) to ensure their homogeneous embedding in the polymer matrices. The phase analysis, composition, morphological and microstructural properties of ZnO NPs and freeze-dried hybrid scaffolds were studied. The compressive strength, porosity, swelling capacity, degradation rate, and antibacterial activity of the hybrid scaffolds were measured. The fabricated 3D scaffolds showed high porosity of up to 78 % with a pore size of about 50–300 μm, good mechanical strength in the range of about 55 kPa, high swelling capacity of up to 505 %, and long-term degradation rate of about 22–25 % for up to 35 days. ZnO NPs have a pure phase and a quasi-spherical shape with a size of about 78 ± 25 nm structure and there are no significant differences between the physicochemical properties of ZnO-free scaffolds and ZnO-loaded scaffolds. Incorporation of ZnO NPs into the scaffolds enhanced their antibacterial response against pathogenic Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This work provides advanced 3D porous hybrid bone scaffolds with favorable mechanical performance and antibacterial activity for bone repair and regeneration.

Densification of transparent hydroxyapatite ceramics via cold sintering process combined with biomineralization

We report for the first time transparent hydroxyapatite (HAp) ceramics densified using a cold sintering process and biomineralization. Under a uniaxial pressure of 800 MPa at 180 °C, granular HAp nanoparticles mixed with simulated body fluid were densified up to 98.5% relative density. During the densification, pseudo-biomineralization occurred among the HAp nanoparticles, leading to the precipitation of a new HAp phase. Additionally, the transformation of granular HAp nanoparticles into nearly circular grains produced fine microstructures with uniform and nanosized grains, reducing light scattering. As a result, the transmittance of 81.6% at λ = 550 nm was achieved. Transparent HAp exhibited Vickers hardness (3.88 ± 0.22 GPa), fracture toughness (0.62 ± 0.03 MPa·m1/2), biaxial flexural strength (41.69 ± 1.23 MPa), and Young's modulus (78.1 ± 2.04 GPa). These findings will pave the way for the fabrication and potential applications of transparent ceramics at low temperatures.

Synthesis and characterisation of magnesium-wrapped hydroxyapatite nanomaterials for biomedical applications

The advancement of novel nanobiomaterials holds significant importance in the fields of drug delivery and environmental remediation. Hydroxyapatite, which falls under the category of bioceramic materials, has demonstrated efficacy as a bone graft material. The substitution of cations in hydroxyapatite has been found to enhance its biological properties, making it a promising material for various biomedical applications. In this study, the synthesis of Mg2+ substituted hydroxyapatite nanostructures was conducted through the sol-gel method employing different surfactants, namely polyethylene glycol and cetyltrimethylammonium bromide. The resulting nanoparticles were subjected to analysis to evaluate their structural, morphological, and optical characteristics. The antimicrobial and antioxidant behavior of the Mg2+ doped hydroxyapatite nanoparticles were also studied. The XRD analysis showed a hexagonal crystal structure for Mg2+ doped hydroxyapatite nanostructures for all samples. The Raman and FTIR results also confirmed the successful substitution of divalent cation Mg2+ in hydroxyapatite. EDAX results exhibited the qualitative elemental composition and stoichiometric nature of synthesized hydroxyapatite. The optical study showed higher transmission in the visible region for the Mg2+ doped hydroxyapatite prepared using various surfactants. The microbial restriction efficacy of Mg2+ doped hydroxyapatite prepared using various surfactants was examined against human pathogenic bacterias Shigella flexneri (MTCC-2197), Escherichia coli (MTCC-4213), Pseudomonas aeruginosa (MTCC-3131), Klebseilla pneumoniae (MTCC-1214), and Staphylococcus aureus (MTCC-3123). The hydroxyapatite nano biomaterial doped with Mg2+ demonstrates remarkable antibacterial, antifungal, and antioxidant properties. The HeLa cell lines exhibited significant cytotoxicity when exposed to magnesium ion-doped hydroxyapatite nanoparticles.

Direct laser microprinting of hydroxyapatite-clad structures by photoreduction-triggered nanomaterial deposition

Hydroxyapatite-based micropatterns were fabricated via near-infrared femtosecond laser irradiation. The micropatterns had a hierarchical cross-section comprising an Ag-based core and an overlying thick layer of non-photosensitive hydroxyapatite nanoparticles. Such micropatterns were continuously formed by the translation of the laser focus in hydroxyapatite nanoparticle-containing AgNO3 solution. A pattern more than quadruple in width was obtained by adding nanoparticles to the solution, despite the same laser irradiation conditions. Raman spectroscopy indicated that the hydroxyapatite nanoparticles retained their crystalline nature even after laser printing. Furthermore, we demonstrate the fabrication of hydroxyapatite-clad patterns on the inner walls of glass capillaries using laser printing.

Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA-pyroptosis pathway in cancer

In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive “cold” tumor types into immuno-responsive “hot” ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

Targetedly Attenuating Cancer Stemness and Plasticity by Homologous Cancer Stem Cell‐Inherited Fusion Membrane Nanoeffectors against Cancer Metastasis

Cancer stem cells (CSCs) are highly related to initiate metastasis and drive tumor relapse/propagation, and the induced cancer stemness and plasticity render cancer intractable to various therapeutic approaches. To address them, a CSC membrane‐based fusion strategy is presented to target and attenuate cancer stemness and plasticity, and accordingly homogenous CSC‐inherited fusion membrane‐coated biomimetic nanoeffectors based on doxorubicin‐loaded hydroxyapatite nanoparticles are engineered. Such biomimetic nanoeffectors coated with fusion membrane consisting of CSCs and cancer cells can not only specifically target the solid breast tumor cells, but also target the latent CSCs. Systematic experiments validate that the constructed nanoeffectors disrupt energy metabolism, trigger lethal mitochondrial apoptosis, remarkably inhibit tumor proliferation, and downregulate the expressions of some target proteins associated with cancer stemness and metastasis to attenuate cancer stemness and the induced plasticity. Contributed by them, such nanoeffectors have been demonstrated to successfully hinder the progression of breast cancer, and decrease lung metastasis in two cancer metastasis mouse models. Such CSCs membrane‐based fusion membrane strategy provides a new candidate avenue rather than the currently dominant immune‐related pathway to repress cancer metastasis via targeting and attenuating cancer stemness.

A Comparative Study on Physicochemical Properties and In Vitro Biocompatibility of Sr-Substituted and Sr Ranelate-Loaded Hydroxyapatite Nanoparticles.

Synthetic hydroxyapatite nanoparticles (nHAp) possess compositional and structural similarities to those of bone minerals and play a key role in bone regenerative medicine. Functionalization of calcium phosphate biomaterials with Sr, i.e., bone extracellular matrix trace element, has been proven to be an effective biomaterial-based strategy for promoting osteogenesis in vitro and in vivo. Functionalizing nHAp with Sr2+ ions or strontium ranelate (SrRAN) can provide favorable bone tissue regeneration by locally delivering bioactive molecules to the bone defect microenvironment. Moreover, administering an antiosteoporotic drug, SrRAN, directly into site-specific bone defects could significantly reduce the necessary drug dosage and the risk of possible side effects. Our study evaluated the impact of the Sr source (Sr2+ ions and SrRAN) used to functionalize nHAp by wet precipitation on its in vitro cellular activities. The systematic comparison of physicochemical properties, in vitro Sr2+ and Ca2+ ion release, and their effect on in vitro cellular activities of the developed Sr-functionalized nHAp was performed. The ion release tests in TRIS-HCl demonstrated a 21-day slow and continuous release of the Sr2+ and Ca2+ ions from both Sr-substituted nHAp and SrRAN-loaded HAp. Also, SrRAN and Sr2+ ion release kinetics were evaluated in DMEM to understand their correlation with in vitro cellular effects in the same time frame. Relatively low concentration (up to 2 wt %) of Sr in the nHAp led to an increase in the alkaline phosphatase activity in preosteoblasts and expression of collagen I and osteocalcin in osteoblasts, demonstrating their ability to boost bone formation.

Comparative evaluation of the effect of 2% graphene oxide and 5% hydroxyapatite nanoparticles in isolation and in combination on micro tensile bond strength of 5th generation adhesive

Graphene is the thinnest, strongest, and stiffest imaginable material. The biocompatible property of graphene oxide can initiate and facilitate cell adhesion, proliferation, and differentiation of periodontal ligament, osteogenic, and oral epithelial cells. Furthermore, the antibiofilm and anti-adhesion properties of graphene oxide in the prevention of dental biofilm infections, dental caries, and dental erosion as well as for implant surface modification and as an anti-quorum sensing agent. Composites are the most often utilized materials for restoration in the field of dentistry due to adhesive resins' improved mechanical and cosmetic properties. To safeguard the dentin and prevent dental cavities, dentin adhesives are utilized to affix hydrophobic resin composites to hydrophilic dentin tissue. Dental adhesives have a harder time adhering to dentin because it contains more water and is less mineralized than enamel. This makes the method more sensitive. As a result, it was chosen to assess and contrast the impact of 5% Hydroxyapatite nanoparticles and 2% Graphene oxide nanoparticles, both separately and together, on the Micro tensile bond strength of 5th generation adhesive. Graphene oxide is the most versatile form of Graphite in structural and functional configuration. Graphene oxide possesses extraordinary physical, chemical, optical, electrical and mechanical properties. Among the graphene family nanomaterials, the reduced form of Graphite adding the oxygenated functional group to the structure increases the surface area and therefore exhibits enviable excellent interaction ability with metal and ions as well as organic species. Graphene oxide in dentistry has provided outstanding results in antimicrobial action, regenerative dentistry, bone tissue engineering, drug delivery, physicochemical properties, enhancement of dental biomaterials and oral cancer treatment.

3D-printed TCP-HA scaffolds delivering MicroRNA-302a-3p improve bone regeneration in a mouse calvarial model

ObjectiveTo demonstrate hydroxyapatite nanoparticles modified with cationic functional molecules. 3-aminopropyltriethoxysilane (HA-NPs-APTES) carrying microRNA-302a-3p (miR) in the 3D-printed tricalcium phosphate/Hydroxyapatite (TCP/HA) scaffold can increase healing of the critical-sized bone defect.Materials and methods3D-printed TCP/HA were modified with HA-NPs-APTES by two methods (M1, M2). The dispersion of particles was visualized by fluorescent microscopy. Biocompatibility of the scaffolds was tested by alizarin assay. Delivery of miR to the cells and osteogenic gene expression were evaluated by qPCR. After selecting best method (M2), scaffolds, scaffolds+HA-NPs-APTES with or without miR were implanted in 4 mm mouse calvarium defect (n = 4 per group). After 2,4 and 6 weeks, bone regeneration were evaluated by microCT and histology sections.ResultsBoth M1 and M2 scaffolds were biocompatible with cell adhesion on its surface. M2 scaffold showed significant increase of miR, suggesting successful delivery, resulted in downregulation of its target mRNA COUP-TFII, and upregulation of RUNX2 mRNA. Calvarium defect with M2 scaffold also showed significantly higher BV/TV and higher number of filled spaces at all time points. Histomorphometry demonstrated new bone formed at the center of the HA-NPs-APTES-miR scaffold earlier than controls.ConclusionTCP/HA scaffold modified with HA-NPs-APTES facilitated delivery of miR and enhanced bone regeneration.