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A reliable method for fabricating biomimetic scaffolds with a controllable mineral gradient to facilitate the surgical repair of tendon-to-bone injuries and the regeneration of the enthesis is reported. The gradient in mineral content is created by sequentially spin-coating with hydroxyapatite/poly(ε-caprolactone) suspensions containing hydroxyapatite nanoparticles in decreasing concentrations. To produce pores and facilitate cell infiltration, the spin-coated film is released and patterned with an array of funnel-shaped microchannels by laser machining. The unique design provided both mechanical (i.e., substrate stiffness) and biochemical (e.g., hydroxyapatite content) cues to spatially control the graded differentiation of mesenchymal stem cells. Immunocytochemical analysis of human mesenchymal stem cell-seeded scaffolds after 14 days of culture demonstrated the formation of a spatial phenotypic cell gradient from osteoblasts to mineralized chondrocytes based on the level of mineralization in the scaffold. By successfully recreating compositional and cellular features of the native tendon enthesis, the biomimetic scaffolds offer a promising avenue for improved tendon-to-bone repair.
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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.
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Diferenciação Celular , Durapatita , Células-Tronco Embrionárias Murinas , RNA Interferente Pequeno , Animais , Camundongos , Durapatita/química , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , RNA Interferente Pequeno/genética , Inativação Gênica , Materiais Biocompatíveis/química , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Nanopartículas/química , Transdução Genética , Interferência de RNA , Técnicas de Silenciamento de GenesRESUMO
The catalytic performance of modified hydroxyapatite nanoparticles, Ca10-xFex-yWy(PO4)6(OH)2, was applied for the degradation of methylene blue (MB), fast green FCF (FG) and norfloxacin (NOR). XPS analysis pointed to the successful partial replacement of Ca by Fe. Under photo-electro-Fenton process, the catalyst Ca4FeII1·92W0·08FeIII4(PO4)6(OH)2 was combined with UVC radiation and electrogenerated H2O2 in a Printex L6 carbon-based gas diffusion electrode. The application of only 10 mA cm-2 resulted in 100% discoloration of MB and FG dyes in 50 min of treatment at pH 2.5, 7.0 and 9.0. The proposed treatment mechanism yielded maximum TOC removal of â¼80% and high mineralization current efficiency of â¼64%. Complete degradation of NOR was obtained in 40 min, and high mineralization of â¼86% was recorded after 240 min of treatment. Responses obtained from LC-ESI-MS/MS are in line with the theoretical Fukui indices and the ECOSAR data. The study enabled us to predict the main degradation route and the acute and chronic toxicity of the by-products formed during the contaminants degradation.
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Eletrodos , Peróxido de Hidrogênio , Ferro , Azul de Metileno , Nanopartículas , Poluentes Químicos da Água , Catálise , Peróxido de Hidrogênio/química , Ferro/química , Azul de Metileno/química , Nanopartículas/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Norfloxacino/química , Durapatita/química , Corantes/química , Processos Fotoquímicos , Raios UltravioletaRESUMO
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.
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Alendronato , Osso e Ossos , Colecalciferol , Micelas , Nanoestruturas , Colecalciferol/química , Nanoestruturas/química , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Alendronato/química , Polietilenoglicóis/química , Humanos , Sistemas de Liberação de Medicamentos , Luminescência , Nanopartículas/química , Portadores de Fármacos/química , Pontos Quânticos/químicaRESUMO
Aim The study aims to characterize Fe and Mg co-substituted hydroxyapatite nanoparticles (FeMgHAPn) and assess the antimicrobial properties of FeMgHAPn-incorporated orthodontic composite. Materials and methods FeMgHAPn was synthesized using the sol-gel method, and the prepared nanoparticle powder was characterized using Fourier Transform Infrared Spectroscopy (FTIR), energy-dispersive X-ray analysis (EDX)) and scanning electron microscopic (SEM) analysis. The FeMgHAPn was incorporated into a commercially available orthodontic composite in two concentrations (40 and 20 µL), and the structure was examined using SEM. The FeMgHAPn-incorporated composite was tested for its antimicrobial efficacy against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli using the agar-well diffusion method. The zones of inhibition (ZOI) were measured in millimeters (mm). Results The characterization of the FeMgHAPn indicated the successful formation of the nanoparticle without any impurities or byproducts. The high concentration (40 µL) of FeMgHAPn-incorporated orthodontic composite showed the maximum ZOI against all three microbes, followed by the low concentration (20 µL) and the control group. Conclusion The FeMgHAPn-incorporated orthodontic composite showed promising antimicrobial activity against caries-causing S. mutans, S. aureus, and E. coli.
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OBJECTIVE: The objective of this study was to evaluate the antimicrobial potential of nanocomposites containing vitamin K2, hydroxyapatite nanoparticles (nHAP), and chitosan (Chito)-coated dental implants against clinically relevant microbial strains. MATERIALS AND METHODS: Four test compounds were prepared: vitamin K2 + nHAP, K2 + Chito + nHAP, vitamin K2, and vitamin K2 + Chito. Agar well diffusion test was conducted to assess the antimicrobial activity of these compounds against Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), Enterococcus faecalis (E. faecalis), and Candida albicans (C. albicans). Results: The vitamin K2 + nHAP nanocomposite exhibited antimicrobial activity against all tested microorganisms, with E. faecalis showing the highest sensitivity (25 mm zone of inhibition at 100 µL concentration). The K2 + Chito + nHAP nanocomposite demonstrated potent antimicrobial activity with C. albicans displaying the highest sensitivity (28 mm zone of inhibition at 100 µL concentration). Pure vitamin K2 showed limited antimicrobial activity, vitamin K2 combined with chitosan exhibited significant susceptibility to C. albicans, resulting in a substantial inhibition zone of 24 mm diameter at a concentration of 100 µL. CONCLUSION: The synergistic effects of vitamin K2 with nHAP and chitosan highlight the potential of these nanocomposites for biomedical applications. These findings contribute to the development of effective nanocomposites to address antimicrobial resistance and improve infection control in various biomedical fields.
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In this study, Hydroxyapatite nanoparticles (HANPs), derived from eggshell waste, were employed to reinforce chitosan biopolymer-based films through the solvent-casting method. The impact of varying HANPs content (1%, 3%, 5%, and 10 wt %) in bionanocomposites was investigated. The influence of HANPs addition on the final film properties was comprehensively analyzed using Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), mechanical (tensile) testing, and Water Vapor Permeability (WVP). The morphological aspects of bionanocomposites and the dispersion of nanoparticles within the matrix were studied using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD). The structural changes in the films were probed using Fourier-Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) techniques. Results indicated that the addition of 1% and 3% of HANPs exhibited a higher glass transition temperature and improved thermal stability in bionanocomposites. Films with 3% HANPs content exhibited a notable increase in tensile strength, showing a 61.54% increase, while films with 1% HANPs content displayed a 52% reduction in WVP compared to pristine chitosan films. These findings underscore the significant potential of chitosan-hydroxyapatite bionanocomposite films for applications in food packaging applications.
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Quitosana , Nanopartículas , Animais , Quitosana/química , Durapatita , Casca de Ovo , Resistência à Tração , Nanopartículas/químicaRESUMO
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.
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Materiais Biocompatíveis , Durapatita , Durapatita/farmacologia , Durapatita/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Osteogênese , Íons/farmacologiaRESUMO
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.
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Lasers de Estado Sólido , Nanopartículas , Humanos , Lasers de Estado Sólido/uso terapêutico , Durapatita/farmacologia , Durapatita/uso terapêutico , Esmalte Dentário , Dureza , Nanopartículas/uso terapêuticoRESUMO
Purified calcium serine metalloprotease from Stenotrophomonas maltophilia strain SMPB12 exhibits highest enzyme activity at pH 9 and temperature range between 15 °C-25 °C. Enzyme supplemented with 40 µM Ca-Hap-NP (NP-protease) showed maximum elevated activity of 17.29 µmole/min/ml (1.9-fold of original protease activity). The thermostability of the enzyme was maintained for 1 h at 60 °C over an alkaline pH range 7.5-10, as compared to the NP untreated enzyme whose activity was of 8.97 µmole/min/ml. A significant loss of activity with EDTA (1.05 µmole/min/ml, 11.75 %), PMSF (0.93 µmole/min/ml, 10.46 %) and Hg2+ (3.81 µmole/min/ml, 42.49 %) was also observed. Kinetics study of NP-protease showed maximum decreases in Km (28.11 %) from 0.28 mM (NP untreated enzyme) to 0.22 mM (NP-protease) along with maximum increase in Vmax (42.88 %) from 1.25 µmole/min/ml to 1.79 µmole/min/ml at varying temperatures. The enhanced activity of NP-protease was able to efficiently degrade recalcitrant solid wastes like feather to produce value-added products like amino acids and helps in declogging recalcitrant solid wastes. The nano-enabled protease may be utilized in a smaller amount for degrading in bulk recalcitrant solid proteinaceous waste at 15 °C temperature as declogging agents providing an eco-friendly efficient process.
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Durapatita , Plumas , Animais , Plumas/metabolismo , Durapatita/metabolismo , Resíduos Sólidos , Peptídeo Hidrolases/metabolismo , Bactérias/metabolismo , Temperatura , Florestas , Concentração de Íons de Hidrogênio , Estabilidade EnzimáticaRESUMO
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. STATEMENT OF SIGNIFICANCE: 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.
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Neoplasias Ósseas , Proteína HMGB1 , Nanopartículas , Osteossarcoma , Ratos , Animais , Durapatita/farmacologia , Durapatita/química , Linfócitos T CD8-Positivos , Osteossarcoma/tratamento farmacológico , Nanopartículas/química , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Age-related musculoskeletal disorders, including osteoporosis, are frequent and associated with long lasting morbidity, in turn significantly impacting on healthcare system sustainability. There is therefore a compelling need to develop reliable preclinical models of disease and drug screening to validate novel drugs possibly on a personalized basis, without the need ofin vivoassay. In the context of bone tissue, although the osteocyte (Oc) network is a well-recognized therapeutic target, currentin vitropreclinical models are unable to mimic its physiologically relevant and highly complex structure. To this purpose, several features are needed, including an osteomimetic extracellular matrix, dynamic perfusion, and mechanical cues (e.g. shear stress) combined with a three-dimensional (3D) culture of Oc. Here we describe, for the first time, a high throughput microfluidic platform based on 96-miniaturized chips for large-scale preclinical evaluation to predict drug efficacy. We bioengineered a commercial microfluidic device that allows real-time visualization and equipped with multi-chips by the development and injection of a highly stiff bone-like 3D matrix, made of a blend of collagen-enriched natural hydrogels loaded with hydroxyapatite nanocrystals. The microchannel, filled with the ostemimetic matrix and Oc, is subjected to passive perfusion and shear stress. We used scanning electron microscopy for preliminary material characterization. Confocal microscopy and fluorescent microbeads were used after material injection into the microchannels to detect volume changes and the distribution of cell-sized objects within the hydrogel. The formation of a 3D dendritic network of Oc was monitored by measuring cell viability, evaluating phenotyping markers (connexin43, integrin alpha V/CD51, sclerostin), quantification of dendrites, and responsiveness to an anabolic drug. The platform is expected to accelerate the development of new drug aimed at modulating the survival and function of osteocytes.
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Osso e Ossos , Osteócitos , Colágeno/química , Hidrogéis , Dispositivos Lab-On-A-ChipRESUMO
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.
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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.
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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.
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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. STATEMENT OF SIGNIFICANCE: 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.
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Nanopartículas , Receptor 4 Toll-Like , Animais , Camundongos , Receptor 4 Toll-Like/metabolismo , Durapatita/farmacologia , Durapatita/metabolismo , Macrófagos/metabolismo , Adjuvantes Imunológicos/farmacologia , Ativação de MacrófagosRESUMO
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. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05685-4.
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Rapid advances in nanotechnology have led to the synthesis and development of various nanomaterials with complex structures and appropriate surface functionalization in recent years. Specifically designed and functionalized nanoparticles (NPs) are increasingly researched and hold great potential in biomedical applications (for example, imaging, diagnostics and therapeutics). Yet, the surface functionalization and biodegradability of NPs play a significant role in their application. Understanding the interactions occurring at the interface between the NPs and the biological components is thus crucial for predicting the fate of the NPs. In this work we study the effect of trilithium citrate functionalization of the hydroxyapatite NPs (HAp NPs) with and without cysteamine modification and their subsequent interaction with hen egg white lysozyme and corroborate the conformational changes of the protein with effective diffusion of the lithium (Li+) counter ion.
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Durapatita , Nanopartículas , Durapatita/química , Desnaturação Proteica , Nanopartículas/química , Proteínas , ÍonsRESUMO
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.
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OBJECTIVE: The purpose of this study was to prepare an orthodontic composite containing hydroxyapatite nanoparticles to prevent demineralization and create a suitable environment for mineral deposition around orthodontic brackets, and to investigate the mechanical and remineralizing properties of the experimental adhesive composite. METHODS: Experimental orthodontic composite were formulated using varying percentages of nano-hydroxyapatite particles. Assessments were based on four groups: a control group (3M™ Transbond™ XT) and experimental composites containing 2% (HA2), 5% (HA5) and 10% (HA10) hydroxyapatite. Vickers Microhardness test was performed to investigate the remineralizing effect in 3 stages: initial stage, after demineralization and after 4 weeks of exposure to artificial saliva. Scanning electron microscopy with energy dispersive X-ray spectroscopy analyser (SEM/EDAX) was used to evaluate hydroxyapatite precipitation and elemental composition of enamel surface. Shear Bond Strength tests were carried out using a universal testing machine and the debonding pattern was assessed using Adhesive Remnant Index (ARI). RESULTS: All groups showed clinically acceptable SBS values. The highest SBS was achieved in the HA2 group, followed by Transbond™ XT, HA5 and HA10. There was no significant difference in the ARI scores. In terms of microhardness properties, HA5 and HA10 demonstrated a significant increase after 4 weeks. The results of SEM analysis showed the precipitation of hydroxyapatite crystals and EDAX analysis indicated the increase of calcium and phosphate ion peaks compared to the demineralized sample. The data were analysed using one-way ANOVA and Tukey's Post-hoc test. CONCLUSIONS: Addition of hydroxyapatite nanoparticles to orthodontic composite can increase the mineral content and microhardness of the adjacent enamel. However, increasing the amount of nanoparticles reduces shear bond strength in a decreasing trend. The above-mentioned findings showed that incremental increase of nanoparticles of HA can be incorporated in composite to a certain extent and limitations are determined by mechanical properties (SBS) required for bracket bonding.