HA NPs Research Articles

Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of −15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC50 values reduced by 6.13-fold and 3.58-fold, respectively. PTX@zein-PEG/HA NPs induced the highest expression levels of apoptotic proteins, particularly PARP, in SKOV3 cells compared to PTX@zein-PEG NPs and free PTX. In summary, PTX@zein-PEG/HA NPs demonstrated potential as a delivery system for PTX in ovarian cancer.

Bone-mimicking scaffold based on silk fibroin incorporated with hydroxyapatite and titanium oxide as enhanced osteo-conductive material for bone tissue formation: fabrication, characterization, properties, and in vitro testing

Bone-mimicking scaffolds based on silk fibroin (SF) mixed with hydroxyapatite nanoparticles (HA NPs) and titanium oxide (TiO2) nanoparticles were created as materials for bone formation. Six scaffold groups were fabricated: S1 (SF), S2 (Silk + (HA: TiO2; 100: 0)), S3 (Silk, (HA: TiO2; 70: 30)), S4 (Silk + (HA NPs: TiO2; 50: 50)), S5 (Silk + (HA: TiO2; 30: 70)), and S6 (Silk + (HA NPs: TiO2; 0:100)). Scaffolds were characterized for molecular formation, structure, and morphology by Fourier transform infrared spectroscopy, element analysis, and X-ray diffraction. They were tested for physical swelling and compressive modulus. Scaffolds were cultured with MC3T3 and tested in vitro to evaluate their biological performance. The results showed that scaffolds with HA and TiO2 demonstrated molecular interaction via amide I and phosphate groups. These scaffolds had smaller pore sizes than those without HA and TiO2. They showed more swelling and higher compressive modulus than the scaffolds without HA and TiO2. They exhibited better biological performance: cell adhesion, viability, proliferation, alkaline phosphatase activity, and calcium content than the scaffolds without HA and TiO2. Their porous walls acted as templates for cell aggregation and supported synthesis of calcium secreted from cells. S3 were the most suitable scaffolds. With their enhanced osteo-conductive function, they are promising for bone augmentation for oral and maxillofacial surgery.

Do silver/hydroxyapatite and zinc oxide nano-coatings improve inflammation around titanium orthodontic mini-screws? In vitro study

Overcoming the failure percentage of orthodontic mini-screws (OMSs), which is about 30% of overall orthodontic cases, especially in malocclusion treatment that requires orthopaedic heavy forces, is a great challenge. Bacterial infections, soft tissue and bone inflammation, and weak connections between bones and the OMS surface are among the main causalities of this failure. The aim of the study is to evaluate in vitro the microbiological activities of the deposited nanomaterials (Silver/hydroxyapatite nanoparticles (Ag/HA NPs) and zinc oxide nanoparticles (ZnO NPs)) in terms of microbial inhibition. In addition, the in-vitro cytotoxicity and cytocompatibility of the synthesized nano-coatings prior to their in-vivo application in animal models were tested on four types of cells, namely, fibroblasts, osteocytes, osteoblasts, and oral epithelial cells. Ag/HA NPs and ZnO NPs were built up onto the surface of titanium OMSs by electrochemical deposition. This electrochemical deposition was performed on 50 orthodontic mini screws and the deposited materials were characterized with the aid of scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) analysis, X-ray Diffraction (XRD) and nano-scratch test. In addition, the microbiological activities of the deposited nanomaterials were explored in vitro in terms of microbial inhibition. Furthermore, the cytotoxicity and cytocompatibility were tested on four types of cells, namely, fibroblasts, osteocytes, osteoblasts and oral epithelial cells. SEM images revealed spherical Ag NPs in the range of 40-70nm in diameter, rod-shaped HA NPs and porous scaly ZnO NPs on the surface of the OMSs. XRD analysis confirmed the crystal structures of AgNPs, HA NPs, and ZnO NPs. ZnO NPs coated OMS had the highest antimicrobial activity than Ag/HA coated OMS against Gram-positive, Gram-negative and fungal strains. Moreover, after incubation, the decrease in the number of bacterial colonies was significant with ZnO and Ag/HA nanoparticles (with the greatest decrease for the former), due to the potent antibacterial effect of nanoparticles against Escherichia coli and Enterococcus faecalis. Moreover, ZnO NPs-coated OMSs showed a better cytocompatibility with oral epithelium, bone cells, and fibroblasts compared to Ag/HA NPs. The suggested nanocoating is a promising strategy to overcome the development of an inflammatory zone around the fixed OMSs.

Ciprofloxacin-Loaded Zein/Hyaluronic Acid Nanoparticles for Ocular Mucosa Delivery.

Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite challenging. To tackle this, nanomedicine presents several advantages compared to conventional ophthalmic dosage forms. Herein, the flash nanoprecipitation technique was applied to produce zein and hyaluronic acid nanoparticles loaded with ciprofloxacin (ZeinCPX_HA NPs). ZeinCPX_HA NPs exhibited a hydrodynamic diameter of <200 nm and polydispersity index of <0.3, suitable for ocular drug delivery. In addition, the freeze-drying of the nanoparticles was achieved by using mannitol as a cryoprotectant, allowing their resuspension in water without modifying the physicochemical properties. Moreover, the biocompatibility of nanoparticles was confirmed by in vitro assays. Furthermore, a high encapsulation efficiency was achieved, and a release profile with an initial burst was followed by a prolonged release of ciprofloxacin up to 24 h. Overall, the obtained results suggest ZeinCPX_HA NPs as an alternative to the common topical dosage forms available on the market to treat conjunctivitis.

Effect of Sugarcane Juice Stabilized Synthesis of Hydroxyapatite Nanoparticles, Characterization and Morphology Studies

In the present work, synthesized sugarcane juice stabilized hydroxyapatite nanoparticles (HA NPs). The synthesis was carried out using different concentrations (5, 10, and 15 ml) of sugarcane juice. The HA-NPs were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope coupled with energy dispersive studies (SEM-EDAX). The morphology and elemental analysis were assessed by transmission electron microscope attached with selected area diffraction (TEM-SAED). The structure and morphology analysis of the synthesized HA-NPs indicate that the particles are crystalline in-phase and spherical. The morphology study of samples indicated that discrete and less agglomerated particles were produced at a high concentration (15 ml) of juice. This study reveals that sugarcane juice acts as a stabilizing agent as well as an organic modifier for the synthesis of HA-NPs.

α1-Acid Glycoprotein-Decorated Hyaluronic Acid Nanoparticles for Suppressing Metastasis and Overcoming Drug Resistance Breast Cancer.

Robust inflammation-suppressing nanoparticles based on α1-acid glycoprotein (AGP)-conjugated hyaluronic acid nanoparticles (AGP-HA NPs) were designed to regulate breast cancer cells’ sensitivity to chemotherapy and to suppress tumor metastasis. The successful conjugation between AGP and HA NPs was confirmed using FTIR, zeta potential, and UV–vis spectroscopy. In vitro studies on MCF-7 cells indicated the remarkable ability of AGP-HA NPs in suppressing migratory tumor ability by 79% after 24 h. Moreover, the efficacy study showed the high capability of AGP-HA NPs in modulating MDA-MB-231 cells and restoring cell sensitivity to the chemotherapeutic drug doxorubicin (DOX). Furthermore, the finding obtained by flow cytometry and confocal spectroscopy demonstrated that AGP-HA NPs enhanced DOX uptake/retention and aided it to reach cell nucleus within 4 h of incubation. Therefore, AGP-HA NPs represent a viable and effective treatment option to strengthen the anticancer effects of chemotherapeutic agents and potentially improve patients’ survival rates.

Hyaluronic Acid-Based Nanoparticles for Protein Delivery: Systematic Examination of Microfluidic Production Conditions.

Hyaluronic acid-based nanoparticles (HA NPs) can be used to deliver a protein cargo to cells overexpressing HA receptors such as CD44 since they combine the low toxicity of the carrier and the retention of the protein integrity with the receptor-mediated internalization. HA properties play a crucial but sometimes unclear role in managing the formation and stability of the meshwork, cell interactions, and ultimately the protein entrapment efficacy. Nowadays, microfluidic is an innovative technology that allows to overcome limits linked to the NPs production, guaranteeing reproducibility and control of individual batches. Taking advantage of this technique, in this research work, the role of HA weight average molecular weight (Mw) in NPs formation inside a microfluidic device has been specifically faced. Based on the relationship between polymer Mw and solution viscosity, a methodological approach has been proposed to ensure critical quality attributes (size of 200 nm, PDI ≤ 0.3) to NPs made by HA with different Mw (280, 540, 710 and 820 kDa). The feasibility of the protein encapsulation was demonstrated by using Myoglobin, as a model neutral protein, with an encapsulation efficiency always higher than 50%. Lastly, all NPs samples were successfully internalized by CD44-expressing cells.

Image-Guided TME-Improving Nano-Platform for Ca2+ Signal Disturbance and Enhanced Tumor PDT.

Dysfunction of the calcium balancing system and disruption of calcium distribution can induce abnormal intracellular calcium overload, further causing serious damage and even cell death, which provides a potential therapeutic approach for tumor treatment. Herein, a nano-platform, which includes UCNPs-Ce6@RuR@mSiO2 @PL-HA NPs (UCRSPH) and SA-CaO2 nanoparticles, is prepared for improving the tumor micro-environment (TME), Ca2+ signal disturbance as well as enhanced photodynamic tumor therapy (PDT). UCRSPH combined with SA-CaO2 can alter TME and relieve hypoxia of the tumor to realize self-reinforcing PDT under near-IR irradiation (980nm). The rutheniumred (RuR) in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles, target Ca2+ channel proteins on the endoplasmic reticulum and mitochondria, sarcoplasmic reticulum Ca2+ -ATPase (SERCA), and mitochondrial calcium uniporter (MCU). The combined participation of nanoparticles and RuR promotes Ca2+ imbalance and cytoplasmic calcium overload with the assistanceof CaO2 , and provides tumor cells higher sensitivity to PDT. Furthermore, the nano-platform also provides fluorescence imaging and calcification computed tomography imaging for in vivo treatment guidance. In conclusion, this image-guided nano-platform show potential for highly specific, efficient combined therapy against tumor cells with minimal side-effects to normal cells by integrating TME improvement, self-reinforcing PDT, and Ca2+ signal disturbance.

A Tumor-Microenvironment-Responsive Nanocomposite for Hydrogen Sulfide Gas and Trimodal-Enhanced Enzyme Dynamic Therapy.

Recently, enzyme dynamic therapy (EDT) has drawn much attention as a new type of dynamic therapy. However, the selection of suitable nanocarriers to deliver chloroperoxidase (CPO) and enhancement of the level of hydrogen peroxide (H2 O2 ) in the tumor microenvironment (TME) are critical factors for improving the efficiency of EDT. In this study, a rapidly decomposing nanocomposite is designed using tetra-sulfide-bond-incorporating dendritic mesoporous organosilica (DMOS) as a nanocarrier, followed by loading CPO and sodium-hyaluronate-modified calcium peroxide nanoparticles (CaO2 -HA NPs). The nanocomposite can effectively generate singlet oxygen (1 O2 ) for tumor therapy without any exogenous stimulus via trimodal-enhanced EDT, including DMOS-induced depletion of glutathione (GSH), H2 O2 compensation from CaO2 -HA NPs in mildly acidic TME, and oxidative stress caused by overloading of Ca2+ . As tetra-sulfide bonds are sensitive to GSH, DMOS can generate hydrogen sulfide (H2 S) gas as a new kind of H2 S gas nanoreactor. Additionally, the overloading of Ca2+ can cause tumor calcification to accelerate in vivo tumor necrosis and promote computed tomography imaging efficacy. Therefore, a novel H2 S gas, EDT, and Ca2+ -interference combined therapy strategy is developed.

NIR Light‐Driven Bi2Se3‐Based Nanoreactor with “Three in One” Hemin‐Assisted Cascade Catalysis for Synergetic Cancer Therapy

AbstractPhotocatalytic semiconductor‐based nanoreactors, that convert nontoxic molecules into toxic ones for cancer therapy, have attracted great interest. However, its therapeutic efficiency is limited by the fast electron–hole recombination within a narrow bandgap, low oxidative damage of H2O2, and tumor hypoxia. Herein, aggregation‐limited hemin is introduced onto Bi2Se3 nanoparticles for successively solving these problems. The nanoreactor (Bi2Se3@hemin‐(G‐H)‐HA NPs) is obtained through adamantane modified hemin and β‐cyclodextrin modified hyaluronic acid complexing and wrapping on Bi2Se3 NPs via host–guest and electrostatic interaction. Once irradiated by NIR light, the hemin assists Bi2Se3 to separate electron–hole pairs and catalyze endogenous H2O to generate vast H2O2, resulting in a 3.9‐fold higher H2O2 generation than that of individual Bi2Se3. Subsequently, H2O2 is catalyzed by aggregation‐limited hemin to generate highly toxic •OH and •O2−, which improves the total reactive oxygen species generation of Bi2Se3@hemin‐(G‐H)‐HA by 10.8‐fold compared to that of Bi2Se3 NPs. Importantly, the cytotoxicity result exhibits a death rate of HepG2 cells of above 90%, even though in a simulated hypoxic environment. Additionally, the in vivo result indicates this nanoreactor realizes an synergetic anticancer effect with a tumor inhibition rate of 92.3%. Overall, such a nanoreactor with hemin‐assisted cascade catalysis is a promising candidate for improving therapeutic efficacy.

Simultaneous fabrication of carbon nanodots and hydroxyapatite nanoparticles from fish scale for biomedical applications.

Fish industries and markets produce large quantities of fish scales, skins, shells, and bone wastes post processing that contaminate the environment and cause health risks in humans. In this context, we have developed a novel and simple integrated process to valorize the Lethrinus lentjan fish scales by fabricate carbon nanodots (CDs) and hydroxyapatite nanoparticles (HA NPs) simultaneously. The fish scale treatment was carried out by hydrothermal method at 280°C that produced CDs and HA NPs simultaneously. Under hydrothermal treatment, organic and inorganic substances of fish scale is transformed to CDs and HA NPs respectively. As TEM images confirmed that fish scale derived CDs were spherically shaped and ~3 to 15nm in size. The CDs exhibited excitation-dependent emission in photoluminescence. The HA NPs were ~8 to 12nm in diameter and ~50 to 100nm in length with rod shape. Also, HA NPs possess spherical shape nanostructures with 15-50nm in diameter. Furthermore, we assessed the cytotoxic behavior of synthesized nanostructures using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. These results showed that synthesized CDs and HA NPs did not cause significant changes in cell viability and morphology, indicating biocompatibility. Additionally, the synthesized CDs and HA NPs were exploited as fluorescent probes for cellular imaging and osteogenic differentiation of stem cells respectively. Overall, the study results indicate that low-cost fish waste was valorized by producing CDs and HA NPs concurrently. The synthesized nanostructures can be applicable for bio-imaging and bone tissue engineering applications.

Development of Novel Nano Hyaluronic Acid Carrier for Diagnosis and Therapy of Atherosclerosis

For an efficient atherosclerosis diagnosis and treatment, we have a persistent requirement of developing a carrier that can precisely carry agents into the pathological location. Herein we examined the ability of hyaluronic acid nanoparticles (HA NPs) as a carrier for the active aiming of atherosclerosis. To prepare HA NPs, 100 mg of Hyaluronic acid was added to 20 ml of formamide, and 61 mg of EDC followed by adding 36.4 mg of NHS in order to activate –COOH functionalities of HA. The resultant mixture was then added with 33.16 mg of aminated 5b-cholanic acid in 40 ml of DMF under contentious stirring at standard temperature conditions for about 12 h, followed by purification and lyophilization. The prepared NPs were examined to study their use in the treatment of atherosclerosis. The prepared HA NPs were studied by using different characterization techniques. By in vitro cellular acceptance investigation, it was exposed that the HA NPs were taken up selectively by over expressing the cells CD44 or stabilin-2. Conversely, the cellular acceptance of HA NPs was noticed to be decreased extremely by pretreating the cells with surplus quantity of free HA, indicating that the HA NPs was taken up by the receptor intervened endocytosis. In conclusion, HA NPs were prepared and confirmed by using different characterization techniques. Also, the prepared HA NPs possesses high ability to be a carrier for the atherosclerosis diagnosis and treatment.

Biosynthesis of Hydroxyapatite Nanoparticles, Characterization for the Treatment of Prostate Cancer in Nursing Care

Hydroxyapatite [Ca10(PO4)6(OH)2] is the one of the major inorganic constituents of natural bone, which has been broadly used in medical and biological applications. The present research work reports on the preparation of hydroxyapatite nanoparticles (HA NPs) via a green and eco-friendly approach based on the use of pectin. The crystalline size, purity and morphology of the as-fabricated HA NPs were studied by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray (EDAX) spectroscopic analysis and scanning electron microscopy (SEM), correspondingly. Further, cytotoxicity investigations showed a dose dependent cytotoxicity towards prostate cancer cells (PC3 cells). Overall, the results illustrated herein suggest that the as-developed HA NPs may offer prospects for the development of drugs for prostate cancer treatment in nursing care for children.

Ultrasonic assisted functionalization of MWCNT and synergistic electrocatalytic effect of nano-hydroxyapatite incorporated MWCNT-chitosan scaffolds for sensing of nitrofurantoin.

In the present work, we report the fabrication of stable composite of chitosan hydrogels (CHI) on multiwalled carbon nanotubes (MWCNT) using a simple ultrasonic-assisted method. Also, rod-like hydroxyapatite nanoparticles (HA NPs) were synthesised using a hydrothermal route and were incorporated into the highly conductive MWCNT-CHI scaffolds using an ultrasonication method. The functionalization of MWCNT and preparation of HA NPs on MWCNT-CHI nanocomposite were done using the sonication over the frequency of 37 kHz with the ultrasonic power capable of 150 W (Elmasonic Easy 60H bath sonicator). The resulting hybrid HA NPs/MWCNT-CHI nanocomposites have an excellent surface area and high surface to volume ratio, which leads to the sensitive detection of nitrofurantoin than pristine MWCNT and HA NPs. The complete elemental and morphological analyses of the HA NPs/MWCNT-CHI nanocomposites were characterised by XRD, FTIR, RAMAN, FESEM, TEM, EDX, and elemental mapping techniques. Electrochemical analysis of the HA NPs/MWCNT-CHI nanocomposites was carried out by cyclic voltammetry, electrochemical impedance spectroscopy and amperometry methods. The modified glassy carbon electrode (GCE) of HA NPs/MWCNT-CHI nanocomposites exhibit the nitrofurantoin detection activity at the linear range of 0.005-982.1 µM with the detection limit of 1.3 nM. The synergistic electrocatalytic activity of HA NPs/MWCNT-CHI nanocomposites modified GCE is correlated to the sensitivity of 0.16 µAµM-1 cm-2 with excellent precision and accuracy towards the sensing of nitrofurantoin.

Hydroxyapatite-poly(vinyl alcohol) core-shell nanoparticles for dual delivery of methotrexate and gemcitabine for bone cancer treatment

The delivery of multiple drugs with bone substitutes is the current strategy for the treatment of bone diseases. In this study, hydroxyapatite nanoparticles (HA NPs) as a core and poly(vinyl alcohol) (PVA) as the corona were developed for the dual delivery of anti-cancer drugs methotrexate (MTX) and gemcitabine (GEM). MTX was conjugated to PVA through ester linkages with a high payload of around 20%. GEM was then physically loaded onto the MTX conjugated-PVA-HA NPs with a loading efficiency of 83%. In vitro drug release studies of GEM-loaded-MTX conjugated-PVA-HA NPs in phosphate buffered saline (pH 7.4) showed a combined release of both MTX (25%) and GEM (60%) at the end of 10 days. Physically loaded MTX showed a burst release of around 50% compared to 16% by conjugated MTX within 24 h which supports the significance of conjugating drug molecules. Cell viability studies using osteosarcoma MG-63 cells confirmed that polymer grafted NPs were non-cytotoxic, while the drug-loaded NPs showed dose-dependent cytotoxicity. The synthesized NPs will be a promising bone-substitute material for the co-delivery of many therapeutic molecules for the treatment of bone diseases.

A chloroplast-inspired nanoplatform for targeting cancer and synergistic photodynamic/photothermal therapy.

Specific targeting capabilities and effective phototherapeutic functions are the key demands for precise cancer phototherapeutic agents. Herein, a bioinspired nanoplatform composed of Cu(ii)-chlorophyll-hyaluronic acid nanoparticles (Cu(ii)Chl-HA NPs) was developed for targeting cancer and synergistic photodynamic/photothermal therapy. Inspired by the photonic biosystem of the chloroplast, Cu(ii) chlorophyll was used as a photosensitive substituent to covalently connect with a hydrophilic HA tail rather than a natural phytol tail, and this conjugate further assembled into a nanoparticle-like morphology under non-covalent interaction. Time-dependent density functional theory calculations reveal that the Cu(ii) chlorophyll has a much smaller energy gap between an excited singlet and excited triplet, and theoretically leads to rapid electron intersystem crossing that would benefit the PDT effect. In addition, a series of experiments have proven that, under 650 nm laser irradiation, the nanoplatform of Cu(ii)Chl-HA can produce a high amount of singlet oxygen and exhibit an outstanding photothermal conversion capability. More interestingly, owing to the specific interactions between the HA component and the CD44 receptor on the cell membrane, the HA tails impart Cu(ii)Chl-HA NPs an excellent receptor-mediated targeting performance toward CD44-overexpressing cancer cells. Based on these features, the nanoplatform of Cu(ii)Chl-HA NPs presents active targeting and outstanding dual modality synergistic PDT/PTT performance of cancer both in vitro and in vivo. Thus, this work opens up a new strategy to fabricate a bioinspired multifunctional cancer phototherapy nanoplatform.

Synthetic anionic surfaces can replace microparticles in stimulating burst coagulation of blood plasma.

Biomaterials are frequently evaluated for pro-coagulant activity but usually in the presence of microparticles (MPs), cell-derived vesicles in blood plasma whose phospholipid surfaces allow coagulation factors to set up as functional assemblies. We tested the hypothesis that synthetic anionic surfaces can catalyze burst thrombin activation in human blood plasma in the absence of MPs. In a thromboelastography (TEG) assay with plastic sample cups and pins, recalcified human citrated platelet-poor plasma spontaneously burst-coagulated but with an unpredictable clotting time whereas plasma depleted of MPs by ultracentrifugation failed to coagulate. Coagulation of MP-depleted plasma was restored in a dose-dependent manner by glass microbeads, hydroxyapatite nanoparticles (HA NPs), and carboxylic acid-containing anionic nanocoatings of TEG cups and pins (coated by glow-discharge plasma-polymerized ethylene containing oxygen, L-PPE:O with 4.4 and 6.8 atomic % [COOH]). Glass beads lost their pro-coagulant activity in MP-depleted plasma after their surfaces were nanocoated with hydrophobic plasma-polymerized hexamethyl disiloxane (PP-HMDSO). In FXII-depleted MP-depleted plasma, glass microbeads failed to induce coagulation, however, FXIa was sufficient to induce coagulation in a dose-dependent manner, with no effect of glass beads. These data suggest that anionic surfaces of crystalline, organic, and amorphous solid synthetic materials catalyze explosive thrombin generation in MP-depleted plasma by activating the FXII-dependent intrinsic contact pathway. The data also show that microparticles are pro-coagulant surfaces whose activity has been largely overlooked in many coagulation studies to-date. These results suggest a possible mechanism by which anionic biomaterial surfaces induce bone healing by contact osteogenesis, through fibrin clot formation in the absence of platelet activation.

Antitumor Effect by Hydroxyapatite Nanospheres: Activation of Mitochondria-Dependent Apoptosis and Negative Regulation of Phosphatidylinositol-3-Kinase/Protein Kinase B Pathway.

Hydroxyapatite nanoparticles (HA NPs) have been acknowledged for their benign biocompatibility and proliferation inhibition effect on tumor cells, attracting considerable attention for tumor therapeutics without late effects. However, unnoticeable tumor cytotoxicity of HA NPs limited the final clinical therapeutic efficacy. Herein, a two-phase synthetic approach was developed to synthesize sphere-like HA NPs by varying the conventional growth habit of HA precipitate. We present our in vitro and in vivo experimental evidence that spherical HA NPs have surprisingly high inhibitory activities against tumor cells. We demonstrate further, based on our experimental data, that the underlying cause for the death of the tumor cells is related to two concurrent pathways, the mitochondria-dependent apoptosis pathway and negative regulation of the phosphatidylinositol-3-kinase/protein kinase B (PIK3/AKT) pathway. The present study indicated that HA nanospheres can be engineered as nontoxic specific inhibitors for efficient tumor therapeutics with nanobiomaterials.

In Vitro Uptake of Hydroxyapatite Nanoparticles and Their Effect on Osteogenic Differentiation of Human Mesenchymal Stem Cells.

There have been many applications in biomedical fields based on hydroxyapatite nanoparticles (HA NPs) over the past decades. However, the biocompatibility of HANPs is affected by exposure dose, particle size, and the way of contact with cells. The objective of this study is to investigate the effect of HA NPs with different sizes on osteogenesis using human mesenchymal stem cells (hMSCs). Three different-sized HA NPs (~50, ~100, and ~150 nm, resp.) were synthesized to study the cytotoxicity, cellular uptake, and effect on osteogenic differentiation of hMSCs. The results clearly showed that each size of HA NPs had dose-dependent cytotoxicity on hMSCs. It was found that HA NPs could be uptaken into hMSCs. The osteogenic differentiation of hMSCs was evaluated through alkaline phosphatase (ALP) activity measurement, ALP staining, immunofluorescent staining for osteopontin (OPN), and real-time polymerase chain reaction (RT-PCR) examination. As expected, HA NPs of all sizes could promote the differentiation of hMSCs towards osteoblast lineage. Among the three sizes, smaller-sized HA NPs (~50 and ~100 nm) appeared to be more effective in stimulating osteogenic differentiation of hMSCs.

Enhanced antibacterial activity, mechanical and physical properties of alginate/hydroxyapatite bionanocomposite film

The effect of hydroxyapatite nanoparticles (HA NPs) contents on the antibacterial activity, physical, and mechanical properties of sodium alginate (SA) film was scrutinized. The samples were prepared via incorporation of three different concentrations of HA NPs (1%, 3%, and 5%) into alginate solution at ambient temperature. In all SA/HA matrices, HA NPs demonstrated considerable bactericidal activity against foodborne pathogen during 12 days. The highest antibacterial effect of SA film was obtained in the presence of 5%HA NPs content and showed 3 CFU/mg reduction. In comparison to pristine alginate, different HA NPs additives enhanced elongation, tensile strength and moisture content of the nanocomposite films. Moreover, water solubility and water vapor permeability of the bionanocomposite were considerably reduced by 50% as the concentration of HA NPs content up to 5%.