The presented study aimed to investigate the effects of Fe3O4 nanoparticles and static magnetic field on osteoblast and osteoclasts' metabolic activity.

Healing of osteoporotic defects is challenging and requires innovative approaches to elicit molecular mechanisms promoting osteoblasts-osteoclasts coupling and bone homeostasis.

This study reports an impact of structure (XRPD, FT-IR) and surface morphology (SEM-EDS) of imatinib-functionalized galactose hydrogels, loaded and unloaded with nHAp, on osteosarcoma cell (Saos-2 and U-2OS) viability, levels of free oxygen radicals, and nitric oxide, levels of BCL-2, p53, and caspase 3 and 9, as well as glycoprotein-P activity. It was investigated how the rough surface of the crystalline hydroxyapatite-modified hydrogel affected amorphous imatinib (IM) release. The imatinib drug effect on cell cultures has been demonstrated in different forms of administration-directly to the culture or the hydrogels. Administration of IM and hydrogel composites could be expected to reduce the risk of multidrug resistance development by inhibiting Pgp.

Osteoporosis results in a severe decrease in the life quality of many people worldwide. The latest data shows that the number of osteoporotic fractures is becoming an increasing international health service problem. Therefore, a new kind of controllable treatment methods for osteoporotic fractures is extensively desired. For that reason, we have manufactured and evaluated nanohydroxyapatite (nHAp)-based composite co-doped with iron oxide (IO) nanoparticles. The biomaterial was used as a matrix for the controlled delivery of miR-21-5p and miR-124-3p, which have a proven impact on bone cell metabolism.

The research has been carried out with a focus on the assessment of the antimicrobial efficacy of pure nanohydroxyapatite, Cu2+-doped nanohydroxyapatite, ozonated olive oil-loaded nanohydroxyapatite, and Cu2+-doped nanohydroxyapatite, respectively. Their potential antimicrobial activity was investigated against Streptococcus mutans, Lactobacillus rhamnosus, and Candida albicans. Among all tested materials, the highest efficacy was observed in terms of ozonated olive oil. The studies were performed using an Ultraviolet-Visible spectrophotometry (UV-Vis), electron microscopy, and statistical methods, by determining the value of Colony-Forming Units (CFU/mL) and Minimal Inhibitory Concentration (MIC).

In response to the demand for new multifunctional materials characterized by high biocompatibility, hydrogel (HG) nanocomposites as a platform for bioactive compound delivery have been developed and fabricated. A specific crosslinking/copolymerization chemistry was used to construct hydrogels with a controlled network organization. The hydrogels were prepared using 3,6-anhydro-α-l-galacto-β-d-galactan (galactose hydrogel) together with resveratrol (trans-3,5,4'-trihydroxystilbene) and calcium hydroxyapatite nanoparticles. The resveratrol was introduced in three different concentrations of 0.1, 0.5, and 1 mM. Nanosized calcium hydroxyapatite was synthesized by a microwave-assisted hydrothermal technique, annealed at 500 °C for 3 h, and introduced at a concentration 10% (m/v). The morphology and structural properties of Ca10(PO₄)₆(OH)₂ and its composite were determined by using XRPD (X-ray powder diffraction) techniques, as well as the absorption and IR (infrared) spectroscopy. The average nanoparticle size was 35 nm. The water affinity, morphology, organic compound release profile, and cytocompatibility of the obtained materials were studied in detail. The designed hydrogels were shown to be materials of biological relevance and of great pharmacological potential as carriers for bioactive compound delivery. Their cytocompatibility was tested using a model of human multipotent stromal cells isolated from adipose tissue (hASCs). The biomaterials increased the proliferative activity and viability of hASCs, as well as reduced markers of oxidative stress. In light of the obtained results, it has been thought that the designed materials meet the requirements of the tissue engineering triad, and may find application in regenerative medicine, especially for personalized therapies.

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.

In the present study, a nanoapatite-mediated delivery system for imatinib has been proposed. Nanohydroxyapatite (nHAp) was obtained by co-precipitation method, and its physicochemical properties in combination with imatinib (IM) were studied by means of XRPD (X-ray Powder Diffraction), SEM-EDS (Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy), FT-IR (Fourier-Transform Infrared Spectroscopy), absorption spectroscopy as well as DLS (Dynamic Light Scattering) techniques. The obtained hydroxyapatite was defined as nanosized rod-shaped particles with high crystallinity. The amorphous imatinib was obtained by conversion of its crystalline form. The beneficial effects of amorphous pharmaceutical agents have been manifested in the higher dissolution rate in body fluids improving their bioavailability. Imatinib-to-hydroxyapatite interactions on the surface were confirmed by SEM images as well as absorption and FT-IR spectroscopy. The cytotoxicity of the system was tested on NI-1, L929, and D17 cell lines. The effectiveness of imatinib was not affected by nHAp modification. The calculated IC50 values for drug-modified nHAp were similar to those for the drug itself. However, higher cytotoxicity was observed at higher concentrations of imatinib, in comparison with the drug alone.

A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp-Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp-Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.

The main aim of our research was to investigate antiadhesive and antibiofilm properties of nanocrystalline apatites doped and co-doped with noble metal ions (Ag+, Au+, and Pd2+) against selected drug-resistant strains of Enterococcus faecalis and Staphylococcus aureus. The materials with the structure of apatite (hydroxyapatite, nHAp; hydroxy-chlor-apatites, OH-Cl-Ap) containing 1 mol% and 2 mol% of dopants and co-dopants were successfully obtained by the wet chemistry method. The majority of them contained an additional phase of metallic nanoparticles, in particular, AuNPs and PdNPs, which was confirmed by the XRPD, FTIR, UV-Vis, and SEM-EDS techniques. Extensive microbiological tests of the nanoapatites were carried out determining their MIC, MBC value, and FICI. The antiadhesive and antibiofilm properties of the tested nanoapatites were determined in detail with the use of fluorescence microscopy and computer image analysis. The results showed that almost all tested nanoapatites strongly inhibit adhesion and biofilm production of the tested bacterial strains. Biomaterials have not shown any significant cytotoxic effect on fibroblasts and even increased their survival when co-incubated with bacterial biofilms. Performed analyses confirmed that the nanoapatites doped and co-doped with noble metal ions are safe and excellent antiadhesive and antibiofilm biomaterials with potential use in the future in medical sectors.

Due to its increased prevalence, osteoporosis (OP) represents a great challenge to health care systems and brings an economic burden. To overcome these issues, treatment plans that suit the need of patients should be developed. One of the approaches focuses on the fabrication of personalized biomaterials, which can restore the balance and homeostasis of disease-affected bone. In the presented study, we fabricated nanometer crystalline hydroxyapatite (nHAp) and iron oxide (IO) nanoparticles stabilized with APTES and investigated whether they can modulate bone cell metabolism and be useful in the fabrication of personalized materials for OP patients. Using a wide range of molecular techniques, we have shown that obtained nHAp@APTES promotes viability and RUNX-2 expression in osteoblasts, as well as reducing activity of critical proinflammatory cytokines while inhibiting osteoclast activity. Materials with APTES modified with nHAp incorporated with IO nanoparticles can be applied to support the healing of osteoporotic bone fractures as they enhance metabolic activity of osteoblasts and diminish osteoclasts' metabolism and inflammation.

Li+/Eu3+ dual-doped calcium apatite analogues were fabricated using a microwave stimulated hydrothermal technique. XRPD, FT-IR, micro-Raman spectroscopy, TEM and SAED measurements indicated that obtained apatites are single-phased, crystallize with a hexagonal structure, have similar morphology and nanometric size as well as show red luminescence. Lithium effectively modifies the local symmetry of optical active sites and, thus, affects the emission efficiency. Moreover, the hydrodynamic size and surface charge of the nanoparticles have been extensively studied. The protein adsorption (lysozyme, LSZ; bovine serum albumin, BSA) on the nanoparticle surface depended on the type of cationic dopant (Li+, Eu3+) and anionic group (OH-, Cl-, F-) of the apatite matrix. Interaction with LSZ resulted in a positive zeta potential, and the nanoparticles had the lowest hydrodynamic size in this protein medium. The cytotoxicity assessment was carried out on the human osteosarcoma cell line (U2OS), murine macrophages (J774.E), as well as human red blood cells (RBCs). The studied apatites were not cytotoxic to RBCs and J774.E cells; however, at higher concentrations of nanoparticles, cytotoxicity was observed against the U2OS cell line. No antimicrobial activity was detected against Gram-negative bacteria with one exception for P. aeruginosa treated with Li+-doped fluorapatite.