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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.

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.

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.

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.

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.

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.

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.

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.

Nano-fertilizers are innovative materials created by nanotechnology methodologies that may potentially replace traditional fertilizers due to their rapid absorption and controlled distribution of nutrients in plants. In the current study, phosphorous-containing hydroxyapatite nanoparticles (nHAP) were synthesized as a novel phosphorus nano-fertilizer using an environmentally friendly green synthesis approach using pomegranate peel (PPE) and coffee ground (CE) extracts. nHAPs were physicochemically characterized and biologically evaluated utilizing the analysis of biochemical parameters such as photosynthetic activity, carbohydrate levels, metabolites, and biocompatibility changes in Punica granatum L. Cytocompatibility with mammalian cells was also investigated based on MTT assay on a Vero cell line. Dynamic light scattering (DLS) and zeta potential analysis were used to characterize the nHAPs for size and surface charge as well as morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The nHAPs were found to have different shapes with average sizes of 229.6 nm, 120.6 nm (nHAPs_PPE) and 167.5 nm, 153 nm (nHAPs_CE) using DLS and TEM, respectively. Overall, the present results showed that the synthesized nHAPs had a negative impact on the selected biochemical, cytotoxic, and genotoxic parameters, indicating that the evaluation of nHAP synthesized by this approach has a wide range of applications, especially as a nano-fertilizer.

Effective biosafe management strategies are used to decrease world crop damage produced by plant-parasitic nematodes. This study evaluated the efficiency of hydroxyapatite nanoparticles (n-HAP) and mycorrhizal fungi to control the Meloidogyne incognita infecting tomato plants. Application of n-HAP significantly increased the juveniles’ mortality (195.67%) and egg hatching inhibition percentage (80.71%) compared to the untreated control, in vitro. Mycorrhizal and/or n-HAP treatments increased the plant growth parameters (root and shoot length, dry weight, and leaf area) and reduced the negative consequence of nematode infection. This may be due to indirect mechanisms through increasing plant nutrient uptake efficiency and increasing the internal plant resistance against nematode infection. In dual-treated plants, phosphorus, nitrogen, and calcium content recorded the highest value in the nematode-infected plants. Whereas the dual inoculation significantly increased mineral contents in tomato plants compared with control, this may induce the strength of the cell wall of the epidermal layer and cortex and consequently increase the plant resistance against nematode infection. Our results revealed that the application of the plant resistance-stimulants enhanced the plant growth parameters and internal nutrient content and reduced the nematode’s criteria. Consequently, the internal plant resistance against nematode infection was induced.

Hydroxyapatite (HAP) has been the gold standard in the biomedical field due to its composition and similarity to human bone. Properties such as shape, size, morphology, and ionic substitution can be tailored through the use of different synthesis techniques and compounds. Regardless of the ability to determine its physicochemical properties, a conclusion for the correlation with the biological response it is yet to be found. Hence, a special focus on the most desirable properties for an appropriate biological response needs to be addressed. This review provides an overview of the fundamental properties of hydroxyapatite nanoparticles and the characterization of physicochemical properties involved in their biological response and role as a drug delivery system. A summary of the main chemical properties and applications of hydroxyapatite, the advantages of using nanoparticles, and the influence of shape, size, functional group, morphology, and crystalline phase in the biological response is presented. A special emphasis was placed on the analysis of chemical and physical interactions of the nanoparticles and the cargo, which was explained through the use of spectroscopic and physical techniques such as FTIR, Raman, XRD, SEM, DLS, and BET. We discuss the properties tailored for hydroxyapatite nanoparticles for a specific biomolecule based on the compilation of studies performed on proteins, peptides, drugs, and genetic material.

The creation of artificial biocomposites consisting of biocompatible materials in combination with bioactive molecules is one of the main tasks of tissue engineering. The development of new materials, which are biocompatible, functional, and also biodegradable in vivo, is a specific problem. Two types of products can be formed from these materials in the processes of biodegradation. The first types of substances are natural for a living organism and are included in the metabolism of cells, for example, sugars, lactic, glycolic, and β-hydroxybutyric acids. Substances that are not metabolized by cells represent the other type. In the latter case, such products should not be toxic, and their concentration when entering the bloodstream should not exceed the established maximum permissible level. The composite materials based on a mixture of biodegradable synthetic and natural polymers with the addition of hydroxyapatite nanoparticles, which acts as a stabilizer of the dispersed system during production of the composite, and which is a biologically active component of the resulting matrix, were obtained and studied. The indirect effect of the shape, size, and surface charge of hydroxyapatite nanoparticles on the structure and porosity of the formed matrix was shown. An in vivo study showed the absence of acute toxicity of the developed composites.

Medical implant use is associated with a risk of infection caused by bacteria on their surface. Implants with a surface that has both bone growth-promoting properties and antibacterial properties are of interest in orthopedics. In the current study, we fabricated a bioactive coating of hydroxyapatite nanoparticles on polyether ether ketone (PEEK) using the sonocoating method. The sonocoating method creates a layer by immersing the object in a suspension of nanoparticles in water and applying a high-power ultrasound. We show that the simple layer fabrication method results in a well-adhering layer with a thickness of 219 nm to 764 nm. Dropping cefuroxime sodium salt (Cef) antibiotic on the coated substrate creates a layer with a drug release effect and antibacterial activity against Staphylococcus aureus. We achieved a concentration of up to 1 mg of drug per cm2 of the coated substrate. In drug release tests, an initial burst was observed within 24 h, accompanied by a linear stable release effect. The drug-loaded implants exhibited sufficient activity against S. aureus for 24 and 168 h. Thus, the simple method we present here produces a biocompatible coating that can be soaked with antibiotics for antibacterial properties and can be used for a range of medical implants.

Hydroxyapatite is one of the most studied biomaterials in the medical and dental field, because of its biocompatibility; it is the main constituent of the mineral part of teeth and bones. In dental science, hydroxyapatite nanoparticles (HAnps) or nano-hydroxyapatite (nano-HA) have been studied, over the last decade, in terms of oral implantology and bone reconstruction, as well in restorative and preventive dentistry. Hydroxyapatite nanoparticles have significant remineralizing effects on initial enamel lesions, and they have also been used as an additive material in order to improve existing and widely used dental materials, mainly in preventive fields, but also in restorative and regenerative fields. This paper investigates the role of HAnps in dentistry, including recent advances in the field of its use, as well as their advantages of using it as a component in other dental materials, whether experimental or commercially available. Based on the literature, HAnps have outstanding physical, chemical, mechanical and biological properties that make them suitable for multiple interventions, in different domains of dental science. Further well-designed randomized controlled trials should be conducted in order to confirm all the achievements revealed by the in vitro or in vivo studies published until now.

The Nutrient Use Efficiency in intensive agriculture is lower than 50% for macronutrients. This feature results in unsustainable financial and environmental costs. Nanofertilizers are a promising application of nanotechnology in agriculture. The use of nanofertilizers in an efficient and safe manner calls for knowledge about the actual effects of nanoproducts on the plant metabolism and eventually on the carrier release kinetics and nutrient accumulation. Hydroxyapatite (Ca10(PO4)6(OH)2) nanoparticles (nHA) have an interesting potential to be used as nanofertilizers. In this study, the effects of different nHA solutions stabilized with carboxymethylcellulose (CMC) were evaluated on germination, seedling growth, and metabolism of Solanum lycopersicum L., used as model species. Our observations showed that the percentage germination of S. lycopersicum is not influenced by increasing concentrations of nHa, while root elongation is strongly stimulated. Tomato plants grown in hydroponics in the presence of nHA have not suffered phytotoxic effects. We conclude that nHA had nontoxic effects on our model plant and therefore it could be used both as a P supplier and carrier of other elements and molecules.

Hydroxyapatite nanoparticles (HAP-NP) are incorporated in oral care products such as toothpastes and mouthwashes to treat dental sensitivity or to promote enamel remineralisation. Despite the good performance of HAP-NP in this application, it is important to ensure its safety for consumers. For that reason, the Scientific Committee on Consumer Safety (SCCS) evaluated the safety of HAP-NP as an oral care ingredient, but the issued opinion was not completely conclusive and the SCCS recommended that additional tests should be performed. Here, we used a commercially available human gingival epithelium (HGE) as a non-animal alternative and MTT cell viability, LDH activity, and IL-1alpha production were evaluated after 3.1% HAP-NP treatment for 10 min, 1 h, and 3 h. Moreover, the absorption of HAP-NP in the gingival tissue was assessed by transmission electron microscopy (TEM) analysis. Finally, the dissolution behaviour of HAP-NP in simulated gastric fluid was also investigated. No deleterious effect was observed for HGE tissues incubated with HAP-NP for all time-points and parameters evaluated. Moreover, a complete dissolution of 3.1% HAP-NP in simulated gastric fluid was observed after 7.5 min at 37 °C. In conclusion, our results evidence the safety of HAP-NP for oral care products with the use of an in vitro replacement alternative for human gingival epithelium and a simulated gastric fluid assay.

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.

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.

Nano-fertilizers are innovative materials created by nanotechnology methodologies that may potentially replace traditional fertilizers due to their rapid absorption and controlled distribution of nutrients in plants. In the current study, phosphorous-containing hydroxyapatite nanoparticles (nHAP) were synthesized as a novel phosphorus nano-fertilizer using an environmentally friendly green synthesis approach using pomegranate peel (PPE) and coffee ground (CE) extracts. nHAPs were physicochemically characterized and biologically evaluated utilizing the analysis of biochemical parameters such as photosynthetic activity, carbohydrate levels, metabolites, and biocompatibility changes in Punica granatum L. Cytocompatibility with mammalian cells was also investigated based on MTT assay on a Vero cell line. Dynamic light scattering (DLS) and zeta potential analysis were used to characterize the nHAPs for size and surface charge as well as morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The nHAPs were found to have different shapes with average sizes of 229.6 nm, 120.6 nm (nHAPs_PPE) and 167.5 nm, 153 nm (nHAPs_CE) using DLS and TEM, respectively. Overall, the present results showed that the synthesized nHAPs had a negative impact on the selected biochemical, cytotoxic, and genotoxic parameters, indicating that the evaluation of nHAP synthesized by this approach has a wide range of applications, especially as a nano-fertilizer.

The creation of artificial biocomposites consisting of biocompatible materials in combination with bioactive molecules is one of the main tasks of tissue engineering. The development of new materials, which are biocompatible, functional, and also biodegradable in vivo, is a specific problem. Two types of products can be formed from these materials in the processes of biodegradation. The first types of substances are natural for a living organism and are included in the metabolism of cells, for example, sugars, lactic, glycolic, and β-hydroxybutyric acids. Substances that are not metabolized by cells represent the other type. In the latter case, such products should not be toxic, and their concentration when entering the bloodstream should not exceed the established maximum permissible level. The composite materials based on a mixture of biodegradable synthetic and natural polymers with the addition of hydroxyapatite nanoparticles, which acts as a stabilizer of the dispersed system during production of the composite, and which is a biologically active component of the resulting matrix, were obtained and studied. The indirect effect of the shape, size, and surface charge of hydroxyapatite nanoparticles on the structure and porosity of the formed matrix was shown. An in vivo study showed the absence of acute toxicity of the developed composites.

Medical implant use is associated with a risk of infection caused by bacteria on their surface. Implants with a surface that has both bone growth-promoting properties and antibacterial properties are of interest in orthopedics. In the current study, we fabricated a bioactive coating of hydroxyapatite nanoparticles on polyether ether ketone (PEEK) using the sonocoating method. The sonocoating method creates a layer by immersing the object in a suspension of nanoparticles in water and applying a high-power ultrasound. We show that the simple layer fabrication method results in a well-adhering layer with a thickness of 219 nm to 764 nm. Dropping cefuroxime sodium salt (Cef) antibiotic on the coated substrate creates a layer with a drug release effect and antibacterial activity against Staphylococcus aureus . We achieved a concentration of up to 1 mg of drug per cm 2 of the coated substrate. In drug release tests, an initial burst was observed within 24 h, accompanied by a linear stable release effect. The drug-loaded implants exhibited sufficient activity against S. aureus for 24 and 168 h. Thus, the simple method we present here produces a biocompatible coating that can be soaked with antibiotics for antibacterial properties and can be used for a range of medical implants.