Electrophoretic Deposition of Calcium Phosphates on Carbon-Carbon Composite Implants: Morphology, Phase/Chemical Composition and Biological Reactions.

Despite a long period of application of metal implants, carbon-carbon medical composites are also widely used for bone defect prosthesis in surgery, dentistry, and oncology. Such implants might demonstrate excellent mechanical properties, but their biocompatibility and integration efficiency into the host should be improved. As a method of enhancing, the electrophoretic deposition of fine-dispersed hydroxyapatite (HAp) on porous carbon substrates might be recommended. With electron microscopy, energy dispersion X-ray and Raman spectroscopy, and X-ray diffraction, we found that the deposition and subsequent heat post-treatment (up to the temperature of 400 °C for 1 h) did not lead to any significant phase and chemical transformations of raw non-stoichometric HAp. The Ca/P ratio was ≈1.51 in the coatings. Their non-toxicity, cyto- and biocompatibility were confirmed by in vitro and in vivo studies and no adverse reactions and side effects had been detected in the test. The proposed coating and subsequent heat treatment procedures provided improved biological responses in terms of resorption and biocompatibility had been confirmed by histological, magnetic resonance and X-ray tomographic ex vivo studies on the resected implant-containing biopsy samples from the BDF1 mouse model. The obtained results are expected to be useful for modern medical material science and clinical applications.

A pilot study of anti-nephrin antibodies in podocytopaties among adults.

AIM: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are podocytopathies characterized by damage to the glomerular filtration barrier, leading to proteinuria and nephrotic syndrome. The production of anti-podocyte antibodies has been proposed as potential circulating factors contributing to the development of these conditions. The aim of the study is to evaluate the levels of anti-nephrin antibodies in patients with podocytopathies and healthy subjects. METHODS: In this study, a total of 77 patients with active glomerulopathy and 11 healthy subjects were included. Forty one patients were diagnosed with FSGS, 11 with MCD, and 25 with MN. To measure the levels of anti-nephrin antibodies, enzyme-linked immunosorbent assay was used. RESULTS: The levels of antibodies to nephrin were significantly higher in patients with MCD 61.2 [28.9-66.3] ng/mL and FSGS 32.5 [17.2-58.4] ng/mL compared to MN 20.3 [14.4-38.4] and healthy individuals 15.3 [12-18.9] ng/mL, p < .05. In patients with primary FSGS, the levels of antibodies to nephrin were significantly higher 45.2 [20-64.3] ng/mL compared to patients with secondary FSGS 26.7 [11.2-44.1] ng/mL, p < .05. There were no significant differences in the remission rate between the anti-nephrin antibodies positive and negative groups (log-rank test: p = .158). CONCLUSION: The level of anti-nephrin antibodies was found to be significantly higher in patients with MCD and pFSGS compared to those with sFSGS, MN, and healthy subjects. Anti-nephrin antibodies in MCD and primary FSGS may be associated with the severity of podocytopathies, however they did not have an impact on the response to therapy.

Preliminary study of anti-CD40 and ubiquitin proteasome antibodies in primary podocytopaties.

Background: Minimal change disease and focal segmental glomerulosclerosis are primary podocytopathies that are clinically presented in adults presenting with severe nephrotic syndrome. The pathogenesis of these diseases is not clear and many questions remain to be answered. A new concept about the role of changes in the antigenic determinant of podocytes and the production of anti-podocyte antibodies that cause podocyte damage is being developed. The aim of the study is to evaluate the levels of anti-CD40 and anti-ubiquitin carboxyl-terminal hydrolase L1 (anti-UCH-L1) antibodies in patients with podocytopathies in comparison with other glomerulopathies. Methods: One hundred and six patients with glomerulopathy and 11 healthy subjects took part in the study. A histological study revealed primary FSGS in 35 patients (genetic cases of FSGS and secondary FSGS in the absence of NS were excluded), 15 had MCD, 21 - MN, 13 - MPGN, 22 patients - IgA nephropathy. The effect of steroid therapy was evaluated in patients with podocytopathies (FSGS and MCD). The serum levels of anti-UCH-L1 and anti-CD40 antibodies were measured by ELISA before steroid treatment. Results: The levels of anti-UCH-L1 antibodies were significantly higher in MCD patients and anti-CD40 antibodies were higher in MCD and FSGS than in the control group and other groups of glomerulopathies. In addition, the level of anti-UCH-L1 antibodies was higher in patients with steroid-sensitive FSGS and MCD, and anti-CD40 antibodies were lower than in patients with steroid-resistant FSGS. An increase in anti-UCH-L1 antibody levels above 6.44 ng/mL may be a prognostic factor of steroid-sensitivity. The ROC curve (AUC = 0.875 [95% CI 0.718-0.999]) for response to therapy showed a sensitivity of 75% and specificity of 87.5%. Conclusion: An increase in the level of anti-UCH-L1 antibodies is specific for steroid-sensitive FSGS and MCD, while an increase in anti-CD40 antibodies - for steroid-resistant FSGS, compared with other glomerulopathies. It suggests that these antibodies could be a potential factor for differential diagnosis and treatment prognosis.

Functionalization of Octacalcium Phosphate Bone Graft with Cisplatin and Zoledronic Acid: Physicochemical and Bioactive Properties.

Bones are the fourth most frequent site of metastasis from malignant tumors, including breast cancer, prostate cancer, melanoma, etc. The bioavailability of bone tissue for chemotherapy drugs is extremely low. This requires a search for new approaches of targeted drug delivery to the tumor growth zone after surgery treatment. The aim of this work was to develop a method for octacalcium phosphate (OCP) bone graft functionalization with the cytostatic drug cisplatin to provide the local release of its therapeutic concentrations into the bone defect. OCP porous ceramic granules (OCP ceramics) were used as a platform for functionalization, and bisphosphonate zoledronic acid was used to mediate the interaction between cisplatin and OCP and enhance their binding strength. The obtained OCP materials were studied using scanning electron and light microscopy, high-performance liquid chromatography, atomic emission spectroscopy, and real-time PCR. In vitro and in vivo studies were performed on normal and tumor cell lines and small laboratory animals. The bioactivity of initial OCP ceramics was explored and the efficiency of OCP functionalization with cisplatin, zoledronic acid, and their combination was evaluated. The kinetics of drug release and changes in ceramics properties after functionalization were studied. It was established that zoledronic acid changed the physicochemical and bioactive properties of OCP ceramics and prolonged cisplatin release from the ceramics. In vitro and in vivo experiments confirmed the biocompatibility, osteoconductivity, and osteoinductivity, as well as cytostatic and antitumor properties of the obtained materials. The use of OCP ceramics functionalized with a cytostatic via the described method seems to be promising in clinics when primary or metastatic tumors of the bone tissue are removed.

Zn-Doped Calcium Magnesium Phosphate Bone Cement Based on Struvite and Its Antibacterial Properties.

The development of magnesium calcium phosphate bone cements (MCPCs) has garnered substantial attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behavior of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0 wt.%-substituted powders. Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter of up to 8 mm. Biological assays confirmed that the developed cement is cytocompatible and promising as a potential bone substitute in reconstructive surgery.

Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages.

SCOPE: Betalain pigments are increasingly highlighted for their bioactive and anti-inflammatory properties, although research is lacking to demonstrate contributions of individual betalains. The work herein aimed to compare effects of four main betalains on inflammatory and cell-protective markers and to highlight potential structure-related relationships of the two main subgroups: betacyanins vs betaxanthins. METHODS AND RESULTS: Murine RAW 264.7 macrophages were stimulated with bacterial lipopolysaccharide following incubation with betacyanins (betanin, neobetanin) and betaxanthins (indicaxanthin, vulgaxanthin I) in concentrations from 1 to 100 µM. All betalains suppressed expression of pro-inflammatory markers IL-6, IL-1ß, iNOS, and COX-2 with tendency for stronger effects of betacyanins compared to betaxanthins. In contrast, HO-1 and gGCS showed mixed and only moderate induction, while more emphasized effects were observed for betacyanins. While all betalains suppressed mRNA levels of NADPH oxidase 2 (NOX-2), a superoxide generating enzyme, only betacyanins were able to counteract hydrogen peroxide induced reactive oxygen species (ROS) generation, in alignment with their radical scavenging potential. Furthermore, betaxanthins exerted pro-oxidant properties, elevating ROS production beyond hydrogen peroxide stimulation. CONCLUSION: In summary, all betalains display anti-inflammatory properties, although only betacyanins demonstrate radical scavenging capacities, indicating potential differing responses under oxidative stress conditions, which requires further research.

Commercial articulated collaborative in situ 3D bioprinter for skin wound healing.

In situ bioprinting is one of the most clinically relevant techniques in the emerging bioprinting technology because it could be performed directly on the human body in the operating room and it does not require bioreactors for post-printing tissue maturation. However, commercial in situ bioprinters are still not available on the market. In this study, we demonstrated the benefit of the originally developed first commercial articulated collaborative in situ bioprinter for the treatment of full-thickness wounds in rat and porcine models. We used an articulated and collaborative robotic arm from company KUKA and developed original printhead and correspondence software enabling in situ bioprinting on curve and moving surfaces. The results of in vitro and in vivo experiments show that in situ bioprinting of bioink induces a strong hydrogel adhesion and enables printing on curved surfaces of wet tissues with a high level of fidelity. The in situ bioprinter was convenient to use in the operating room. Additional in vitro experiments (in vitro collagen contraction assay and in vitro 3D angiogenesis assay) and histological analyses demonstrated that in situ bioprinting improves the quality of wound healing in rat and porcine skin wounds. The absence of interference with the normal process of wound healing and even certain improvement in the dynamics of this process strongly suggests that in situ bioprinting could be used as a novel therapeutic modality in wound healing.

A cross-sectional study of antibodies to ubiquitin proteasome system in different glomerulopathies.

BACKGROUND: Recently, evidence has emerged that the ubiquitin system, which is involved in extracellular protein degradation, is most susceptible to damage in podocytes in cases of podocytopathies. We studied anti-ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) antibodies in glomerulopathies with proteinuria. MATERIALS AND METHODS: 71 patients with glomerulopathy and 11 healthy subjects were included in our study. 44 patients had nephrotic syndrome, and 27 did not. Serum levels of anti-UCHL1 antibodies were measured by ELISA. RESULTS: The levels of anti-UCHL1 antibodies were significantly higher in focal segmental glomerulosclerosis (FSGS) patients than in minimal change disease (MCD), IgA nephropathy, membranous nephropathy, or membranoproliferative glomerulonephritis patients and control group. The levels of UCHL1 antibodies in serum did not correlate with 24-hour proteinuria, blood pressure, glomerulosclerosis percentage, or area of tubulointerstitial fibrosis, but did correlate with serum creatinine and estimated glomerular filtration rate (eGFR). During the development of the ROC curve (AUC = 0.766 (95% CI 0.634 - 0.897)) for FSGS vs. other forms of glomerulopathies, a readjustment of the sensitivity of 75% and specificity of 61% were established. A former increase in anti-UCHL1 antibody levels above 1.93 ng/mL may be a marker of FSGS OR 3.617 (95% CI 1.051 - 12.447), p = 0.041. CONCLUSION: An increase in the level of anti-UCHL1 antibodies in the serum was noted in FSGS, which suggests that these antibodies could be a potential biomarker for FSGS patients.

Strontium Substituted ß-Tricalcium Phosphate Ceramics: Physiochemical Properties and Cytocompatibility.

Sr2+-substituted ß-tricalcium phosphate (ß-TCP) powders were synthesized using the mechano-chemical activation method with subsequent pressing and sintering to obtain ceramics. The concentration of Sr2+ in the samples was 0 (non-substituted TCP, as a reference), 3.33 (0.1SrTCP), and 16.67 (0.5SrTCP) mol.% with the expected Ca3(PO4)2, Ca2.9Sr0.1(PO4)2, and Ca2.5Sr0.5(PO4)2 formulas, respectively. The chemical compositions were confirmed by the energy-dispersive X-ray spectrometry (EDX) and the inductively coupled plasma optical emission spectroscopy (ICP-OES) methods. The study of the phase composition of the synthesized powders and ceramics by the powder X-ray diffraction (PXRD) method revealed that ß-TCP is the main phase in all compounds except 0.1SrTCP, in which the apatite (Ap)-type phase was predominant. TCP and 0.5SrTCP ceramics were soaked in the standard saline solution for 21 days, and the phase analysis revealed the partial dissolution of the initial ß-TCP phase with the formation of the Ap-type phase and changes in the microstructure of the ceramics. The Sr2+ ion release from the ceramic was measured by the ICP-OES. The human osteosarcoma MG-63 cell line was used for viability, adhesion, spreading, and cytocompatibility studies. The results show that the introduction of Sr2+ ions into the ß-TCP improved cell adhesion, proliferation, and cytocompatibility of the prepared samples. The obtained results provide a base for the application of the Sr2+-substituted ceramics in model experiments in vivo.

A non-randomized comparative study of olfactory and gustatory functions in children who recovered from COVID-19 (1-year follow-up).

The experimental group included 68 children over 6 years of age who had recovered from COVID-19. The control group included 22 children over 6 years of age who have never had COVID-19. Research methods included neurological examination, verification of cognitive status, examination by an otolaryngologist, and smell and taste assessment. The examination was performed 6-8 weeks after COVID-19 recovery and after 1 year in some patients. Children who recovered from COVID-19 had a reduction in their ability to smell compared to children who had never had COVID-19. The olfactory thresholds and taste identification scores after recovery from COVID-19 were identical, whether the parents had reported anosmia in their children during COVID-19 or not, and irrespective of hyperthermia level and the presence or absence of headache and hyperhidrosis during COVID-19. Analysis of correlation with neuropsychiatric symptoms showed no differences in the olfactory thresholds in children irrespective of the presence of neuropsychiatric symptoms (tics, tremors, enuresis, compulsive movements, seizures, speech disorders, attention deficit, and easy fatigability) both in general, and in particular among subjects performing or not any compulsive movements, and experiencing or not a combination of easy fatigability and daytime sleepiness. Evidence suggests that in children and adolescents, partial hyposmia is associated with depressive symptoms, varying in severity from low to high, but symptoms of depression were not caused by COVID-19 infection itself. Analysis in subgroups with different degrees of state and trait anxiety did not reveal any significant differences in the olfactory threshold. A re-examination of 21 children was performed after 1 year. An objective olfactometric examination showed that the sensitivity to odorants increased significantly. In 1 year, we compared the thresholds of smell in children who had COVID-19 and those who did not have this disease: olfactory sensitivity after COVID-19 in children is restored to normal values. Schulte correction test showed that none of 14 children with asthenic manifestations in the form of fluctuations or exhaustion when performing the test immediately after COVID-19 had these manifestations after 1 year. Thus, asthenization of cognitive activity was recorded within the next 1.5 months after suffering from COVID-19 but was absent after 1 year.

Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells.

The present study aimed to compare the absorption and transport patterns of three main betalains, betanin, vulgaxanthin I and indicaxanthin, into intestinal epithelial cells and to assess their distinct molecular effects on inflammatory and redox-related cell signalling in association with their radial scavenging potencies. All three betalains showed anti-inflammatory effects (5-80 µM), reflected by attenuated transcription of pro-inflammatory mediators such as cyclooxygenase-2 and inducible NO-synthase. Concomitant increases in antioxidant enzymes such as heme oxygenase-1 were only observed for betanin. Moreover, betanin uniquely demonstrated a potent dose-dependent radical scavenging activity in EPR and cell-based assays. Results also indicated overall low permeability for the three betalains with Papp of 4.2-8.9 × 10-7 cm s-1. Higher absorption intensities of vulgaxanthin and indicaxanthin may be attributed to smaller molecular sizes and greater lipophilicity. In conclusion, betanin, vulgaxanthin I and indicaxanthin have differentially contributed to lowering inflammatory markers and mitigating oxidative stress, implying the potential to ameliorate inflammatory intestinal disease. Compared with two betaxanthins, the greater efficacy of betanin in scavenging radical and promoting antioxidant response might, to some extent, compensate for its poorer absorption efficiency, as demonstrated by the Caco-2 cell model.

Multipurpose made colorimetric materials for amines, pH change and metal ion detection.

Sensors are routinely developed for specific applications, but multipurpose sensors are challenging, due to stability and poor functional design. We report organic materials that operate in solution and gas phase. They show a strong response behaviour to at least three types of environmental changes: pH, amine and metal ion binding/detection. We have confirmed and validated our findings using various analytical and computational methods. We found that the changes in polarity of the solvent and pH not only red shift the tail of the absorption spectra, but also extend the peak optical absorption of these structures by up to 100 nm, with consequential effects on the optical gap and colour changes of the materials. Acid-base response has been studied by spectrophotometric titrations with trifluoroacetic acid (TFA) and triethyl amine (TEA). The experiments show excellent reversibility with greater sensitivity to base than acid for all compounds. Analysis into metal sensing using Zn(ii) and Cu(ii) ions as analytes show that the materials can successfully bind the cations forming stable complexes. Moreover, a strong suppression of signal with copper gives an operative modality to detect the copper ion as low as 2.5 × 10-6 M. The formation of the metal complexes was also confirmed by growing crystals using a slow diffusion method; subsequent single crystal X-ray analysis reveals the ratio of ligand to metal to be 2 to 1. To test sensitivity towards various amine vapours, paper-based sensors have been fabricated. The sensors show a detection capability at 1 ppm of amine concentration. We have employed CIE L*a*b* colour space as the evaluation method, this provides numeric comparison of the samples from different series and allows comparison of small colour differences, which are generally undetectable by the human-eye. It shows that the CIE L*a*b* method can assess both sensitivity to a particular class of analytes and a specificity response to individual amines in this subclass offering an inexpensive and versatile methodology.

Novel approach for purification of major betalains using flash chromatography and comparison of radical scavenging and antioxidant activities.

The present study focused on the development of a new purification protocol suitable for betanin and other major betalains, vulgaxanthin I, indicaxanthin and neobetanin, using flash chromatography which is a convenient and fast method to isolate unstable materials. Following preliminary tests, a gradient procedure using 0-60% acetonitrile, with 0.1% (v/v) formic acid as mobile phase, was selected for the purification. Different fractions were collected based on UV detection at 254 and 280 nm and purities were confirmed by reverse-phase HPLC analysis to be 97%, 95%, 79% and 52% for betanin, indicaxanthin, vulgaxanthin I, and neobetanin, respectively, with pigment yields ranging from 120 to 487 mg per 100 g of powdered raw material. Comparative assessment of antioxidant and radial scavenging properties of individual betalains indicated highest potential for betanin followed by neobetanin, vulgaxanthin I and indicaxanthin.

Serum levels of plasminogen activator urokinase receptor and cardiotrophin-like cytokine factor 1 in patients with nephrotic syndrome.

The pathogenesis of primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) remains unknown to date. Some circulating permeability factors are being discussed. This work assessed molecule candidates for permeability in serum samples of patients with nephrotic syndrome (NS). MATERIALS AND METHODS: 41 patients with chronic glomerulonephritis (CGN) were included in our study. 17 patients had FSGS, 7 patients had MCD, 5 patients had membranoproliferative glomerulonephritis (MPGN), 6 patients had IgA nephropathy, and 6 patients had membranous nephropathy (MN). The laboratory data were compared with the clinical and histological features of nephritis. Serum levels of plasminogen activator urokinase receptor (uPAR) and cardiotrophin-like cytokine factor 1 (CLCF-1)were measured by ELISA. RESULTS: The serum levels of uPAR were higher in FSGS patients before treatment than in patients with other morphological forms (MCD, IgA nephropathy, MN, and MPGN). The levels of uPAR in serum did not correlate with daily proteinuria, serum creatinine/eGFR, arterial hypertension, the number of sclerosed glomeruli, or tubulointerstitial fibrosis. No correlations were found between the levels of CLCF-1 in serum and creatinine levels/glomerular filtration rate, the percentage of sclerosed glomeruli, or the severity of tubulointerstitial fibrosis. There were no significant differences between the histological variants of nephritis. However, we found correlations between CLCF-1 levels and proteinuria and lipid levels. CONCLUSION: The data indicate an increase in the serum uPAR levels of FSGS before treatment. CLCF-1 levels in serum do not depend on histological forms of CGN, kidney function, or immunosuppressive treatment, but they correlate with proteinuria and serum lipids in patients with NS.

Mesoporous Iron(III)-Doped Hydroxyapatite Nanopowders Obtained via Iron Oxalate.

Mesoporous hydroxyapatite (HA) and iron(III)-doped HA (Fe-HA) are attractive materials for biomedical, catalytic, and environmental applications. In the present study, the nanopowders of HA and Fe-HA with a specific surface area up to 194.5 m2/g were synthesized by a simple precipitation route using iron oxalate as a source of Fe3+ cations. The influence of Fe3+ amount on the phase composition, powders morphology, Brunauer-Emmett-Teller (BET) specific surface area (S), and pore size distribution were investigated, as well as electron paramagnetic resonance and Mössbauer spectroscopy analysis were performed. According to obtained data, the Fe3+ ions were incorporated in the HA lattice, and also amorphous Fe oxides were formed contributed to the gradual increase in the S and pore volume of the powders. The Density Functional Theory calculations supported these findings and revealed Fe3+ inclusion in the crystalline region with the hybridization among Fe-3d and O-2p orbitals and a partly covalent bond formation, whilst the inclusion of Fe oxides assumed crystallinity damage and rather occurred in amorphous regions of HA nanomaterial. In vitro tests based on the MG-63 cell line demonstrated that the introduction of Fe3+ does not cause cytotoxicity and led to the enhanced cytocompatibility of HA.

Classic highlights in porphyrin and porphyrinoid total synthesis and biosynthesis.

Porphyrins feature prominently in nature, be it as enzymatic cofactors, electron and exciton shuffles, as photoactive dyes, or as signaling substances. Their involvement in the generation, storage and use of oxygen is pivotal to life, while their photochemical properties are central to the biochemical functioning of plants. When complexed to metals, porphyrins can engage in a multitude of contemporary applications ranging from solar energy generation to serving as catalysts for important chemical reactions. They are also able to function as useful theranostic agents, and as novel materials for a wide range of applications. As such, they are widely considered to be highly valuable molecules, and it almost goes without saying that synthetic organic chemistry has dramatically underpinned all the key advances made, by providing reliable access to them. In fact, strategies for the synthesis of functionalized porphyrins have now reached a state of refinement where pretty well any desired porphyrin can successfully be synthesized with the approaches that are available, including a cornucopia of related macrocycle-modified porphyrinoids. In this review, we are going to illustrate the development of this exciting field by discussing a number of classic syntheses of porphyrins. Our coverage will encompass the natural protoporphyrins and chlorophylls, while also covering general strategies for the synthesis of unsymmetrical porphyrins and chlorins. Various industrial syntheses of porphyrins will also be discussed, as will other routes of great practical importance, and avenues to key porphyrinoids with modified macrocycles. A range of selected examples of contemporary functionalization reactions will be highlighted. The various key syntheses will be described and analyzed from a traditional mechanistic organic chemistry perspective to help student readers, and those who are new to this area. The aim will be to allow readers to mechanistically appreciate and understand how many of these fascinating ring-systems are built and further functionalized.

The Influence of Co Additive on the Sintering, Mechanical Properties, Cytocompatibility, and Digital Light Processing Based Stereolithography of 3Y-TZP-5Al2O3 Ceramics.

Nanocrystalline 3 mol% yttria-tetragonal zirconia polycrystal (3Y-TZP) ceramic powder containing 5 wt.% Al2O3 with 64 m2/g specific area was synthesized through precipitation method. Different amounts of Co (0-3 mol%) were introduced into synthesized powders, and ceramic materials were obtained by heat treatment in the air for 2 h at 1350-1550 °C. The influence of Co addition on the sintering temperature, phase composition, microstructure, mechanical and biomedical properties of the obtained composite materials, and on the resolution of the digital light processing (DLP) printed and sintered ceramic samples was investigated. The addition of a low amount of Co (0.33 mol%) allows us to decrease the sintering temperature, to improve the mechanical properties of ceramics, to preserve the nanoscale size of grains at 1350-1400 °C. The further increase of Co concentration resulted in the formation of both substitutional and interstitial sites in solid solution and appearance of CoAl2O4 confirmed by UV-visible spectroscopy, which stimulates grain growth. Due to the prevention of enlarging grains and to the formation of the dense microstructure in ceramic based on the tetragonal ZrO2 and Al2O3 with 0.33 mol% Co the bending strength of 720 ± 33 MPa was obtained after sintering at 1400 °C. The obtained materials demonstrated the absence of cytotoxicity and good cytocompatibility. The formation of blue CoAl2O4 allows us to improve the resolution of DLP based stereolithographic printed green bodies and sintered samples of the ceramics based on ZrO2-Al2O3. The developed materials and technology could be the basis for 3D manufacturing of bioceramic implants for medicine.

Influence of Al on the Structure and in Vitro Behavior of Hydroxyapatite Nanopowders.

Nanopowders of aluminum-substituted (0-20 mol %) hydroxyapatite (HA) with the average size of 40-60 nm were synthesized by the precipitation method from nitrate solutions. A series of samples were studied by various analytical tools to elucidate the peculiarities of Al introduction. Electron paramagnetic resonance and pulsed electron-nuclear double resonance data demonstrate that incorporation of Al resulted in a decrease in the concentration of impurity carbonate anions and lead to an increase in the number of protons in the distant environment of the impurity nitrogen species. Density functional theory calculations show that the Al3+ incorporation is accompanied by the local positional rearrangement and the distortion of anion channel geometry. An in vitro test conducted on MG-63 cells demonstrates the cytocompatibility and magnification of the surface matrix characteristics with Al doping.

Human Platelet Lysate Sustains the Osteogenic/Adipogenic Differentiation Potential of Adipose-Derived Mesenchymal Stromal Cells and Maintains Their DNA Integrity in vitro.

Human platelet lysate (HPL) is a promising alternative to fetal calf serum (FCS) for the expansion of adipose tissue mesenchymal stromal cells (AT-MSCs) for translational medicine applications. However, some biological effects of HPL are still to be elucidated. We aimed to compare complex characteristics, such as cell morphology, proliferative activity, differentiation potential, and especially monolayer recovery, DNA integrity, and the gene expression pattern, between AT-MSCs cultured with HPL or FCS. Primary AT-MSC cultures were expanded in medium containing FCS or pooled HPL. Cell growth and proliferation were estimated by cell doubling time and the monolayer formation rate, while migration was assessed by wound-healing assay. The capacity for adipogenic and osteogenic differentiation was evaluated by alkaline phosphatase and Oil Red O staining. DNA integrity was evaluated by comet assay, and analysis of gene expression by real-time PCR. Media supplemented with HPL or FCS provided a similar surface immunophenotype, cell morphology (except some cell dimensions and a bigger colony size in HPL), DNA integrity, and rate of wound healing. Meanwhile, AT-MSC proliferated more intensively in HPL-supplemented media (especially at 5% HPL) and had a reduced doubling population time. AT-MSC in HPL had increased adipogenic potential and similar osteogenic potential in comparison with FCS. Our results indicate the feasibility and evident prospects for the use of pooled HPL as an alternative to FCS and safe non-xenogenic growth supplement for ex vivo expansion of clinical-grade AT-MSCs for regenerative medicine purposes.

Fabrication of Hybrid Materials from Titanium Dioxide and Natural Phenols for Efficient Radical Scavenging against Oxidative Stress.

Oxidative stress caused by free radicals is one of the great threats to inflict intracellular damage. Here, we report a convenient approach to the synthesis, characterization, and evaluation of the radical activity of titanium-based composites. We have investigated the potential of natural antioxidants (curcumin, quercetin, catechin, and vitamin E) as radical scavengers and stabilizers. The titanium oxide composites were prepared via three steps including sol-gel synthesis, carboxylation, and esterification. The characterization of the titanium-phenol composites was carried out by FTIR, PXRD, UV-vis and SEM methods. The radical scavenging ability of the novel materials was evaluated using DPPH and an in vitro LPO assay using isolated rat liver mitochondria. The novel materials exhibit both a higher stability and an antioxidant activity in comparison to bare TiO2. It was found that curcumin and quercetin based composites show the highest antioxidant efficiency among the composites under study followed by catechin and vitamin E based materials. The results from an MTT assay carried out on the Caco-2 cell line indicate that the composites do not contribute to the cytotoxicity in vitro. This study demonstrates that a combination of powerful antioxidants with titanium dioxide can change its functional properties and provide a convenient strategy against oxidative stress.