Incorporation of Barium Ions into Biomaterials: Dangerous Liaison or Potential Revolution?

In the present manuscript, a brief overview on barium, its possible utilization, and the aftermath of its behavior in organisms has been presented. As a bivalent cation, barium has the potential to be used in a myriad of biochemical reactions. A number of studies have exhibited both the unwanted outcome barium displayed and the advantages of barium laden compounds, tested in in vitro and in vivo settings. The plethora of prospective manipulations covered the area of hydrogels and calcium phosphates, with an end goal of examining barium’s future in the tissue engineering. However, majority of data revert to the research conducted in the 20th century, without investigating the mechanisms of action using current state-of-the-art technology. Having this in mind, set of questions that are needed for possible future research arose. Can barium be used as a substitute for other biologically relevant divalent cations? Will the incorporation of barium ions hamper the execution of the essential processes in the organism? Most importantly, can the benefits outweigh the harm

Fusion and classification algorithm of octacalcium phosphate production based on XRD and FTIR data

The present manuscript tested an automated analysis sequence to provide a decision support system to track the OCP synthesis from -TCP over time. Initially, the XRD and FTIR signals from a hundredfold scaled-up hydrolysis of OCP from -TCP were fused and modeled by the curve fitting based on the significantly established maxima from the literature and nine features extracted from the fitted shapes. Afterward, the analysis sequence enclosed the machine learning techniques for feature ranking, spatial filtering, and dimensionality reduction to support the automatic recognition of the synthesis stages. The proposed analysis pipeline for OCP identification might be the foundation for a decision support system explicitly targeting OCP synthesis. Future projects will exploit the suggested methodology for pinpointing the OCP production over time (including the intermediary phases present in the OCP formation) and for evaluating whether biological variables might be merged with biomaterial properties to build a unified model of tissue response to the implant

Doxorubicin loaded octacalcium phosphate particles as controlled release drug delivery systems: Physico-chemical characterization, in vitro drug release and evaluation of cell death pathway

: Mastering new and efficient ways to obtain successful drug delivery systems (DDS) with controlled release became a paramount quest in the scientific community. Increase of malignant bone tumors and the necessity to optimize an approach of localized drug delivery require research to be even more intensified. Octacalcium phosphate (OCP), with a number of advantages over current counterparts is extensively used in bone engineering. The aim of the present research was to synthesize bioactive and biocompatible doxorubicin (DOX) containing OCP particles. DOX-OCP was successfully obtained in situ in an exhaustive range of added drug (1-20 wt%, theoretical loading). Based on XRD, above 10 wt% of DOX, OCP formation was inhibited and the obtained product was low crystalline α-TCP. In-vitro drug release was performed in pH 7.4 and 6.0. In both pH environments DOX had a continuous release over six weeks. However, the initial drug burst for pH 7.4, in the first 24 h, ranged from 15.9 ± 1.3 % to 33.5 ± 12 % and for pH 6.0 23.7 ± 1.5 % to 36.2 ± 12 %.The DOX-OCP exhibited an inhibitory effect on viability of osteosarcoma cell lines MG63, U2OS and HOS. In contrast, MC3T3-E1 cells (IC50 > 0.062 μM) displayed increased viability and proliferation from 3rd to 7th day. Testing of the DDS on ferroptotic markers (CHAC1, ACSL4 and PTGS2) showed that OCP-DOX does not induce ferroptotic cell death. Moreover, the evaluation of protein levels of cleaved PARP, by western blotting analysis, corroborated that apoptosis is the main pathway of programmed cell death in osteosarcoma cells induced by DOX-OCP

Octacalcium Phosphate-Laden Hydrogels on 3D-Printed Titanium Biomaterials Improve Corrosion Resistance in Simulated Biological Media

| openaire: EC/H2020/860462/EU//PREMUROSA Funding Information: Financial support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie ITN “Premurosa” (GA 860462) is gratefully acknowledged. The authors also acknowledge the access to the infrastructure and expertise of the BBCE—the Baltic Biomaterials Centre of Excellence (European Union’s Horizon 2020 research and innovation program under the grant agreement No. 857287). Publisher Copyright: © 2023 by the authors.The inflammatory-associated corrosion of metallic dental and orthopedic implants causes significant complications, which may result in the implant’s failure. The corrosion resistance can be improved with coatings and surface treatments, but at the same time, it might affect the ability of metallic implants to undergo proper osteointegration. In this work, alginate hydrogels with and without octacalcium phosphate (OCP) were made on 3D-printed (patterned) titanium alloys (Ti Group 2 and Ti-Al-V Group 23) to enhance their anticorrosion properties in simulated normal, inflammatory, and severe inflammatory conditions in vitro. Alginate (Alg) and OCP-laden alginate (Alg/OCP) hydrogels were manufactured on the surface of 3D-printed Ti substrates and were characterized with wettability analysis, XRD, and FTIR. The electrochemical characterization of the samples was carried out with open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS). It was observed that the hydrophilicity of Alg/OCP coatings was higher than that of pure Alg and that OCP phase crystallinity was increased when samples were subjected to simulated biological media. The corrosion resistance of uncoated and coated samples was lower in inflammatory and severe inflammatory environments vs. normal media, but the hydrogel coatings on 3D-printed Ti layers moved the corrosion potential towards more nobler values, reducing the corrosion current density in all simulated solutions. These measurements revealed that OCP particles in the Alg hydrogel matrix noticeably increased the electrical charge transfer resistance at the substrate and coating interface more than with Alg hydrogel alone.Peer reviewe

An integrative approach in developing scaffolds based on gellan gum and bioactive glass aimed for osteochondral tissue engineering

Bilayer scaffolds based on gellan gum (GG) and nanoparticulate bioactive-glass (BAG) were developed by an integrative approach based on engineering principles and characterization in biomimetic bioreactors. The osteo-inductive GG-BAG layer containing 2 % w/w GG and 2 % w/w BAG (composition: 70 n/n % SiO2, 30 n/n % CaO) was produced by gelation followed by freeze-drying to obtain open porosity in axial and radial directions. The chondral layer was obtained by dispensing a warm 2 % w/w GG solution at 60˚C over the frozen macroporous GG-BAG layer at -25˚C. The temperatures were optimized by applying a one-dimensional unsteady-state heat transfer model so to obtain a thin integration zone, 0.5 – 1 mm thick. The scaffolds were evaluated regarding bioactivity in a biomimetic bioreactor with specially designed chambers to provide supply of two media relevant for chondral and bone tissues. In the present experiment, simulated body fluid (SBF) was supplied countercurrently continuously during 14 days of the experiment (1.1 ml min-1 flowrate), while dynamic compression (5 % deformation, 0.68 Hz frequency, 337.5 µm s-1 loading rate, 1 h / day) was applied on the chondral layer, from day 7 to day 14. SEM analyses have confirmed the retained integrity of the scaffolds, as well as formation of hydroxyapatite (HAp) uniformly throughout the osteo-layer of the scaffolds.Significantly higher bioactivity under biomimetic conditions compared to static controls resulted in slightly but significantly increased compression modulus. These results indicated a high potential of the applied integrative strategy for the development of biomimetic bilayer scaffolds

Synthesis, solvatochromism, and biological activity of novel azo dyes bearing 2-pyridone and benzimidazole moieties

New azo dyes bearing 2-pyridone and benzimidazole moieties were prepared using diazotization of 4-(1H-benzo[d]imidazol-2-yl)aniline and coupling of the obtained diazonium salt with substituted 3-cyano-2-pyridones. Obtained compounds were characterized via UV-Vis, FT-IR, and H-1 and C-13 NMR spectroscopy as well as by elemental analysis data. The UV-Vis spectra of the synthesized dyes were measured in thirteen solvents of different properties at room temperature. Solvatochromism and tautomerism of novel azo dyes were discussed. An MTT (3,4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test was performed to prove the biocompatibility of the investigated dyes. The investigated dyes exhibited satisfying antiproliferative activities against both tumor cell lines, MDA-MB-231 and HCT-116, demonstrating the potent capacity for treatment of tumors

Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment

: Research on biomaterials typically starts with cytocompatibility evaluation, using the ISO 10993-5 standard as a reference that relies on extract tests to determine whether the material is safe (cell metabolic activity should exceed 70 %). However, the generalized approach within the standard may not accurately reflect the material's behavior in direct contact with cells, raising concerns about its effectiveness. Calcium phosphates (CaPs) are a group of materials that, despite being highly biocompatible and promoting bone formation, still exhibit inconsistencies in basic cytotoxicity evaluations. Hence, in order to test the cytocompatibility dependence on different experimental setups and material-cell interactions, we used amorphous calcium phosphate, α-tricalcium phosphate, hydroxyapatite, and octacalcium phosphate (0.1 mg/mL to 5 mg/mL) with core cell lines of bone microenvironment: mesenchymal stem cells, osteoblast-like and endothelial cells. All materials have been characterized for their physicochemical properties before and after cellular contact and once in vitro assays were finalized, groups identified as 'cytotoxic' were further analyzed using a modified Annexin V apoptosis assay to accurately determine cell death. The obtained results showed that indirect contact following ISO standards had no sensitivity of tested cells to the materials, but direct contact tests at physiological concentrations revealed decreased metabolic activity and viability. In summary, our findings offer valuable guidelines for handling biomaterials, especially in powder form, to better evaluate their biological properties and avoid false negatives commonly associated with the traditional standard approach