Multifunctional nano scale drug delivery particles based on vitamin D3-loaded hydroxyapatite in bone tissue engineering

Specific group of controlled drug delivery systems in bone tissue engineering are multifunctional nanoparticle systems (MNPs) based on hydroxyapatite coated with drug loadedbioresorbable polymer. This study illustrates the possibility for controlled synthesis of multifunctional nanoparticulate forms based on hydroxyapatite as a system for local delivery of vitamin D3 and secondary delivery of defect filler hydroxyapatite. The results were two type of nanoparticle powder of controlled shapes, sizes and properties: hydroxyapatite nano particles as vitamin D3 carriers (HAp/D3) and vitamin D3-loaded hydroxyapatite coated with poly-D,Llactide-co-glycolide (HAp/D3/PLGA) with particle sizes of d50=68 nm and d50=71 nm, respectively. Simultaneously, biocompatibility of the materials was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. Biocompatibility tests carried out on cell cultures have shown intact monolayers of epithelial cells in contact with both materials and no negative effects on the cell viability. The aim of this work was application in living/human systems, and it has been tested in vivo; artificially made bone defects of a mandible damaged by osteoporosis have been reconstructed with both types of materials. The best results were achieved 24 weeks after implantation of vitamin D3-loaded hydroxyapatite coated with poly-D,L-lactide-co-glycolide. Accelerated angiogenesis, vascularization, osteogenesis and bone structure differentiation has been achieved in the presence of specific islet-like forms of ossification centers

Multifunctional nano particulate systems based on hydroxyapatite as systems for local delivery of vitamin D3

Multifunctional drug delivery system based on hydroxyapatite may be a research challenge in the treatment and reconstruction of bone tissue. Vitamin D3 has a positive effect on osteogenesis as it increases osteoblast differentiation and mineralization of bone tissue. The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new multifunctional nanoparticulate system for local delivery of vitamin D3 suitable for applications in bone engineering. The synthesis, characterization and application of three nano particle systems was shown: hydroxyapatite, hydroxyapatite/vitamin D3 and hydroxyapatite/PLGA/vitamin D3. The obtained vitamin D3-loaded nanoparticles based on hydroxyapatite. Characterization was performed with wide-angle X-ray structural analysis (XRD), infrared spectroscopy (FT-IR), field-emission scanning electron microscopy (FESEM), zeta potential (ZP) and particle sized distribution (PSD) methods. Basic in vitro studies were performed implantation of materials in rats. XRD and FT-IR analyses confirmed that the vitamin D3 is loaded hydroxyapatite and PLGA. Different values of zeta potential may refer to different phenomenological processes during in vivo studies

Comparative study of the effects of different nanomaterials on the viability of human osteoblast-like cells

The aim of this study was to compare the effects of two types of nanomaterials, cobalt-exchanged hydroxyapatite (CoHAp) and calcium phosphate/poly-(DL-lactide-co-glycolide) (CP/PLGA), on the viability of Saos-2 osteoblast-like cells, using MTT test. We have examined the suspension of this materials in the following concentrations: 1.6, 8, 40, 200, 1000 and 2500 μg/ml, as well as extracts in concentration range from 2,5% to 100%. Both materials showed cytotoxic effect at higher concentrations of suspension and extract, respectively, but they were not cytotoxic at lower concentrations. CP/PLGA acted stronger cytotoxic compared to CoHAp, regardless of whether it is examined suspension or extract. CoHAp in small concentrations of suspension and extract acted slightly stimulatory on cells. This suggests that CoHAp may have advantage for use in the in vivo systems

Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties

Composite biomaterials based on nano-hydroxyapatite have an enormous potential for natural bone tissue reparation, filling and augmentation. Multifunctional nanoparticulate systems based on HAp coated with biocompatible and bioresorbable polymers make a separate group of filler systems in bone tissue engineering [1,2]. Chitosan has many physicochemical (reactive OH and NH2 groups) and biological (biocompatible, biodegradable) properties that make it an attractive material for use in bone tissue engineering. However, chitosan may induce thrombosis and it is therefore unsuitable as blood – contacting biomaterial. One of the strategies to improve the biocompatibility of chitosan is combination of this biopolymer with compounds that exhibit complementary properties. In our studies, we present the synthesis, characterization, in vitro and in vivo research of a particulate form of nano HAp-coated polymer systems. We synthesized nanoparticulate HAp coated with chitosan (Ch) and a chitosan-poly-D,L-lactide-co-glycolide (Ch-PLGA) polymer blend obtained via the solvent/non-solvent method and freeze-drying processing. We also examined the possibility of using Thermo-Gravimetric Analysis/Differential-Thermal Analysis (DTA/TGA) coupled on-line with mass spectrometry (MS) as a finger print for identification purposes in coating processes. The quantitative antimicrobial test has shown that HAp/Ch-PLGA have some antibacterial properties (MIC (mg/mL): Pseudomonas aeruginosa – 6.40, Staphylococcus aureus – 6.40, Staphylococcus epidermidis – 3.20). MTT assay was used to test cytotoxicity and cell viability. By using HAp/Ch-PLGA in the form of a filler a high level of reparatory ability, with the presence Haversian canals and cement lines in reconstructed of bone defect, was achieved in vivo. [1] N. Ignjatovic, C. Liu, J. Czernuszka, D. Uskokovic, Micro and nano/injectable composite biomaterials containing calcium phosphate coated with poly(dl-lactide-co-glycolide), Acta Biomaterialia, 3 (2007) 927-935 [2] N. Ignjatović, V. Uskoković, Z. Ajduković, D. Uskoković, Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol, Materials Science and Engineering: C 33 (2013) 943–95

Joint effects of vitamin D and nanobiomaterial in the jaw bone regeneration

Systems for targeted delivery of drugs with high affinity for specific organs, tissues, and cells were introduced at the beginning of the twentieth century. Recently, this concept is attracting much attention. These systems have shown most effective in reducing adverse effects of drugs. In recent years, scientists have created a system of nanoparticles for delivery of vitamin D. Special attention is paid to the role of vitamin D in the division and differentiation of osteoblasts and thus, in its role in osteogenesis. In this regard it was interesting to observe the local effects of the active form of vitamin D3 in osteogenesis, as a part of the system for local delivery. These effects were observed on an experimental model. Three types of nanobiomaterial were implanted in the artificially made defects in rats’ mandibular bone. Six weeks after implantation of hydroxyapatite, hydroxyapatite-coated vitamin D3 and hydroxyapatite nanoparticles coated with vitamin D3 mixed with the polymer, the animals were sacrificed, and the samples of mandibular alveolar bone were taken. The samples were adequately prepared and subjected to histopathological analysis. The best results in regeneration of osteoporotic jaw bone were obtained in the experimental group of animals where the implant was hydroxyapatite-coated vitamin D3 mixed with the polymer. The results show that nanobiomaterials with local delivery of active form of vitamin D3, used in this study, may be materials of the future in the area of weakened jaw bone tissue regeneration

Evaluation of glassionomer cement application for permanent binding of prosthetic dentures

Fixed dentures are created in order to rehabilitate the function of orofacial system, to correct disordered interdental relation, as well as the relation between jaws and to do esthetic correction. Binding of fixed dentures to the teeth carriers is done with a layer of binding biomaterials from the group of dental cements. Cement as the choice of dental biomaterials has to be the best cement for the most frequent, routine management for these type of works and most frequently used materials – metal, acrylate, ceramics. Cement must be safe to use with patients. Ideally, it must have longtime advantages such as to be for various uses, to find the right balance between results and simplicity of application, which are the most important for routine management. There are many types of cement. In this study, Zn-phosphate and glassionomer cement were used. In modern dental technology, production of cement is well developed and the most concerns are about non-toxicity, biocompatibility, bioinertion, biofunction. In some cases acidic balance disorder of saliva medium can bring to release of low doses of heavy metal ions after the reaction of cement and heavy metal ions from dental compounds. In this study, the best results were achieved with glassionomer cement, because the lowest percent of released heavy metal ions in saliva medium was noticed after cementing of fixed dentures by glassionomer cement. Because of its characteristics, glassionomer cement can be the choice material for permanent cementing of fixed prosthetic dentures

Examination of the influence of nanomaterials calcium phosphate/poly(DL-lactide-co-glycolide) and cobalt-exchanged hydroxyapatite on the viability of Saos-2 cells

We have examined the effect of extracts of the calcium phosphate/poly(DL-lactide-co-glycolide) (CP/PLGA) and cobalt-exchanged hydroxyapatite (CoHAp), on the viability of Saos2 osteoblastlike cells. Extracts were prepared by incubation for 3 days at 37°C in the cultivation medium. Conductivity and pH value of extracts were measured before viability assay. Cell viability was estimated by MTT test performed after 24 h incubation of cells with various concentrations of extracts. Extract of CP/PLGA acted more cytotoxic on osteoblasts than the extract of CoHAp. This difference in the effect of examined extracts can be explained by their different pH value and conductivity

Multifunctional nano scale drug delivery particles based on vitamin D3-loaded hydroxyapatite in bone tissue engineering

Specific group of controlled drug delivery systems in bone tissue engineering are multifunctional nanoparticle systems (MNPs) based on hydroxyapatite coated with drug loadedbioresorbable polymer. This study illustrates the possibility for controlled synthesis of multifunctional nanoparticulate forms based on hydroxyapatite as a system for local delivery of vitamin D3 and secondary delivery of defect filler hydroxyapatite. The results were two type of nanoparticle powder of controlled shapes, sizes and properties: hydroxyapatite nano particles as vitamin D3 carriers (HAp/D3) and vitamin D3-loaded hydroxyapatite coated with poly-D,Llactide-co-glycolide (HAp/D3/PLGA) with particle sizes of d50=68 nm and d50=71 nm, respectively. Simultaneously, biocompatibility of the materials was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. Biocompatibility tests carried out on cell cultures have shown intact monolayers of epithelial cells in contact with both materials and no negative effects on the cell viability. The aim of this work was application in living/human systems, and it has been tested in vivo; artificially made bone defects of a mandible damaged by osteoporosis have been reconstructed with both types of materials. The best results were achieved 24 weeks after implantation of vitamin D3-loaded hydroxyapatite coated with poly-D,L-lactide-co-glycolide. Accelerated angiogenesis, vascularization, osteogenesis and bone structure differentiation has been achieved in the presence of specific islet-like forms of ossification centers

The success rate of hydroxyapatite nanoparticles coated with bioresorbable polymers in a biological environment

Hydroxyapatite (HAp) nanoparticles coated with bioresorbable polymers have been successfully used as filler, carriers of antibiotics, vitamins and stem cells in bone tissue engineering. Interactions in the microenvironment of nanoparticulate hydroxyapatites and tissues are of a particular interest and present a challenge in regenerative medicine. The phenomena that influence the success of targeting and controlled operation or therapeutic nanosystems are numerous and complex: size, shape, surface charge, functional groups of nanoparticles, electrical double-layer formation, zeta potential, partial molar free energy, sorption molar free energy, isoelectric point of solid–liquid interface; receptor–ligand binding interactions of nano-bio interface etc. In our studies we present the synthesis, characterization, in vitro and in vivo research of nanoparticulate form of HAp-coated polymers systems. Synthesized nanoparticulate HAp coated with different types of bioresorbable polymers: poly(D,L-lactide-co-glycolide), chitozan and other similar by the solvent/non-solvent method. The physical and chemical analyses have confirmed that HAp particles are coated with bioresorbable polymers. Results of spectroscopic analysis suggests formation of hydrogen bonds between the surface groups of HAp and =O and –H groups in the polymer chain from bioresorbable polymers. By adding nanoparticulate HAp in the polymer matrix was achieved the changes in the partial molar free energy and sorption molar free energy of the system. In vitro results showed satisfactory biocompatibility of nanoparticulate HAp-coated polymers systems. The use of these systems in the form of filler was achieved a high quality osteogenesis in reconstruction of bone tissue, in vivo.The biodistribution of 125I-labeled HAp particles after intravenous injection in rats showed the potential use of these materials as a organ-targeting system: uncoated-HAp mostly targeted the liver, coated-HAp spleen and lungs

Application analysis of micro and nano composites in restoring of bone tissue of the jaw

Application of synthetic polymer biomaterials is very often used in biomedicine and dentistry. That’s why the need for creating the new polymer biomaterials is more and more obvious. Hydroxy-apatite, as a natural constituent of bone, has been already used for many years in all segments of dentistry. In order to develop better properties, hydroxy-apatite is combined with polymers. In this research, application of micro and nano composite biomaterials in reconstruction of osteoporosis damaged alveolar bone of rats is analyzed. Evaluation of regeneration of restored osteoporosis damaged alveolar bone of rats was done by histopathological analyses. The optimal results were after 24 weeks after implantation of calcium-phosphate/poly-D, L-lactide-co-glycolide (CP/DLPLG) composite biomaterials nano particles in comparison to micro particles. Regeneration and reparation of damaged alveolar bone with creation of new bone tissue which is very similar to mature bone, are much better on the place of nano CP/DLPLG implantation. Because of its very good osteoconductive effect, applied nano CP/DLPLG composite can totally renew lost bone tissue, so it can be the material of choice for the alveolar bone defect rehabilitation