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Evaluation of biofunctional composite cement: integrating magnesium phosphate and alginate hydrogel

The characteristic of injectability is crucial within the realm of biofunctional materials, enhancing their application in minimally invasive surgical procedures. In this context, bone cements, particularly magnesium phosphate cement (MPC), are prominently utilized due to their excellent resorption rates, high mechanical strength, and quick curing times, positioning them as strong competitors against traditional ceramic cements. Nonetheless, MPC is not without its challenges, including issues of brittleness, paste susceptibility to washout, and difficulties with injectability. This investigation focuses on the advantages of integrating alginate hydrogel into MPC, with the goal of improving its operational effectiveness and overall performance characteristics.

The synthesis of ceramic cement was executed through the combination of magnesium oxide and potassium dihydrogen phosphate (4:1 Mg/P molar ratio), incorporating varying concentrations of sodium alginate (SA) solutions as the liquid phases and adjusting powder-to-liquid ratios accordingly. The hydrogel was formed through a delayed cross-linking reaction using CaCO₃/GDL. Subsequently, the cement pastes were shaped and incubated under standardized conditions. Comprehensive assessments were performed, including evaluations of setting time and temperature, microstructure, chemical and phase composition, mechanical strengths, injectability, biodegradation, and cytocompatibility.

A novel dual-setting biocomposite cement was effectively created. The production of well-crystallized k-struvite crystals, showing significant variances in size and growth patterns, in conjunction with the cross-linked SA, was confirmed. Our analyses demonstrate numerous advantages of these new cements, such as decreased setting times, diverse microstructural configurations, improved biodegradability, and enhanced paste cohesion and injectability. Nevertheless, these advancements negatively impacted the composite's mechanical strength. Notwithstanding elevated bioreactivity, the cements retained cytocompatibility across most evaluated groups.

Acknowledgments
This research was supported by the Gdańsk University of Technology by the DEC-3/2022/IDUB /III.4.3/Pu grant under the PLUTONIUM 'Excellence Initiative – Research University program.

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Advancements in biofunctional dual-setting bone cements: The potential of pHEMA hydrogel enhancement for magnesium phosphate cement

Bone regeneration capabilities are inherent to skeletal tissue. However, the integration of specialized biomaterials is frequently necessary, enhancing and sometimes being crucial to the bone healing process. Bone cements are particularly notable within this context as they exhibit biofunctionality. Specifically, magnesium phosphate cement (MPC) is recognized for its quick setting, high mechanical strength, and osteogenic benefits, despite issues like brittleness and injection complications. This study presents a novel MPC-based cement enhanced with poly(2-hydroxyethyl methacrylate) (HEMA) hydrogel, aimed at overcoming these limitations.

The novel cement formulation includes a powder mix of tri-magnesium phosphate and di-ammonium hydrogen phosphate at a 4:1 ratio, combined with HEMA solutions (15-25%). Polymerization, initiated by APS/TEMED, with different premixing times, facilitates hydrogel formation. Specimen preparation involved mixing the above components at a 2.5 g/mL ratio, subsequently putting the obtained paste into molds, and curing them (24h, 37°C, >90% humidity). Evaluations covered setting time, SEM microstructure, XRD and FTIR analyses, mechanical strengths, porosity, degradation rate, and cytocompatibility with human osteoblasts.

Key findings indicate that incorporating HEMA hydrogel markedly impacts the primary properties of MPC. Specifically, alterations in the concentration of HEMA and the duration of premixing significantly influence the creation of hydrogel aggregates within the cement matrix, contributing to enhanced mechanical properties and facilitating controlled degradation. Importantly, although the modified cement demonstrated advantageous functional and mechanical properties, future research should prioritize exploring alternative hydrogel formulations or modifications to the HEMA polymerization process.

Acknowledgment: This research was partially supported by the Gdańsk University of Technology by the DEC-3/2022/IDUB /III.4.3/Pu grant under the PLUTONIUM 'Excellence Initiative – Research University program.

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Bismuth apatites as the basis of biomaterials for bone tissue regeneration
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Compounds with apatite structures containing bismuth, of the compositions Ca10-2xBixNax(PO4)6F2 (x = 1, 2, 3, 4), Ca8BiNa(PO4)6O and Ca8BiNa(PO4)5,5(VO4)0,5O, were synthesized by a solid-phase reaction for the first time. The phase identity and crystal structure features of the substances were studied by X-ray diffraction analysis (Rietveld method) and IR spectroscopy. It was found that calcium, bismuth and sodium ions are distributed on cationic positions of the apatite crystal structure, not statistically, but taking into account coordination possibilities. Thus, sodium ions, possessing high values of coordination numbers, are located in the centers of three-caped triangular bipyramids (CN = 9, Wyckoff position 4f), and bismuth ions are located in in the centers of two-caped triangular bipyramids (CN = 8, Wyckoff position 6h). Calcium is distributed uniformly over the positions. Such peculiarity of the crystal structure of substances causes strong binding of bismuth ions, and, therefore, prevents their exit from the structure. The phase stability (stability) of the substances in water, phosphate-salt buffer and trypsin was confirmed by X-ray phase and elemental analyses, which confirmed the prediction of behavior made on the basis of structural data. The absence of cytotoxicity of the materials was confirmed directly in the standard MTT test. For the Ca8BiNa(PO4)6F2 and Ca6Bi2Na2(PO4)6F2 compositions, an increase in cell proliferation was observed. This phenomenon can be explained by the fact that these substances are formed as spheroidal particles during synthesis, which facilitates their penetration through the cell membrane. In addition, it was found that Ca8BiNa(PO4)6O and Ca8BiNa(PO4)5,5(VO4)0,5O do not possess bactericidal activity against S. aureus and E. coli cultures, which also agrees with the previously mentioned conclusions. Thus, new non-cytotoxic materials based on bismuth apatite were obtained.

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Fabrication of a Hydroxyapatite coating reinforced with Functionalized graphene oxide deposited on a NiTi implant alloy: A bioactivity and electrochemical property analysis

The majority of the challenges within the broad application of titanium alloys used as biomedical implants are related to their interfacial properties; thus, surface modification represents a proper solution to overcome these issues. Surface functionalization by coating deposition is an appropriate choice for metallic implant surface modification [1]. In particular, inorganic ceramic coatings such as hydroxyapatite (HAp, Ca10(PO4)6(OH)2) have been widely employed to improve this incompatibility [2]. Nevertheless, the brittle nature and poor strength of HAp coatings are a problem, especially when the implant needs to work under load-bearing conditions. Therefore, the incorporation of nanoparticles as secondary bioactive fillers enhances their characteristics [3]. This work aims to investigate the effect of graphene oxide (GO) nanolayers functionalized with therapeutic cations as an active/passive filler to increase the bioactivity of an HAp coating and hinder the access of corrosive species to the metallic substrate. The release ability of functionalized graphene oxide (FGO) makes it a desirable candidate as a bioactive additive for bone regeneration. The flake morphology of these nanoparticles can enhance the barrier performance and the toughness of the HAp coating [4].

For this purpose, GO nanoparticles have been synthesized via the modified Hummer method and have been functionalized through absorption of strontium and gallium cations. Then, an HAp coating loaded with Sr/Ga-functionalized GO nanoparticles was deposited on nitinol samples. The effect of FGO incorporation on the anticorrosion behaviour of HAp-coated nitinol samples was studied via polarization and electrochemical impedance spectroscopy (EIS). Furthermore, the bioactivity and antibacterial performance of the composite coatings applied on implant samples have also been investigated.

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Surface decoration of PEEK implants with IGF-1 via polydopamine enhances osseointegration and osteogenic differentiation

Polyetheretherketone (PEEK) is a promising biomedical material in orthopedic and dental applications owing to its excellent mechanical properties, near absent immune toxicity, and X-radiolucency, but suffers from bio-inertness and inferior osteoconduction. Surface modification of PEEK can effectively solve this problem, retaining most of its advantageous properties. In this study, porous structures were fabricated using concentrated sulfuric acid, and the interface was bio-functionalized by IGF-1 immobilization on the porous surface via a polydopamine coating. The surface characteristics of modified PEEK were evaluated via scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The pore size was generally distributed between 0.3 and 0.8 µm and was evaluated using ImageJ software. The hydrophilicity and BSA protein adsorption capacity were significantly enhanced after dopamine coating. IGF-1 was successfully immobilized onto the porous surface via the polydopamine coating and the immobilization efficiency was determined via ELISA. The tensile mechanics study showed that although the surface porous structure maintained a Young's modulus similar to that of human bone, the elongation at break and the maximum yield strength decreased. The in vitro studies revealed that PEEK immobilized with IGF-1 could remarkably improve the attachment, spreading, proliferation, extracellular matrix secretion, and alkaline phosphatase (ALP) activity of MC3T3-E1 pro-osteoblasts. These findings indicate that IGF-1 modification on the surface of PEEK implants using pDA as an intermediate layer can significantly enhance the osseointegration and osteogenic differentiation potential of PEEK, which has great potential for clinical applications.

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Changing of mechanical properties of Polylactic Acid-based materials during biodegradation

Arthrodesis is a surgical procedure whose aim is to fix an affected joint to compensate for the lost function of the limb. Nowadays, the common materials for these purposes are medical steel and titanium alloys. However, metal alloys have high mechanical characteristics compared to natural bone. This leads to stress shielding at the bone–implant contact. Also, these implants cannot provide joint fixation at a physiological angle for patients under anesthesia.

The current problems can be solved by developing a self-positioning individualized implant made of composite material with shape memory effect. The materials presented in this research are polylactic acid (PLA) filled with bioinert (SiO2) and bioactive (hydroxyapatite) particles. The mechanical properties of the composites are close to those of natural bone. Also, PLA is a biodegradable material, which means that the implant can gradually dissolve inside the body. This peculiarity leads to changing mechanical properties over time, but also helps to avoid repeated surgery. This research is focused on how different conditions of biodegradation affect the mechanical characteristics of PLA- SiO2 and PLA-HAp composites.

Composites with 10, 15 and 20% mass of fillers and pure PLA were produced by extrusion. The process of degradation was observed on flat samples (ISO 14125:1998) to determine the flexural properties of the materials. The samples were immersed in phosphate-buffered saline, blood serum and cell solution to compare the differences in biodegradation mechanisms. The samples were kept in solutions at 37℃ for 1, 2, 4 and 8 weeks. Then, they were tested by mass change, surface SEM and three-point bending.

The results demonstrated changes in the degree of crystallinity and a significant decrease in the mechanical properties of the samples during the process of biodegradation. These were caused by the paramount destruction of the amorphous phase of the polymer.

This study was performed with the support of Grant RNF № 24-23-00442.

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Green synthesis of Ag or Au nanoparticles for antimicrobial applications using wild consortia of SCOBY-based membranes

The green synthesis of bioactive nanoparticles (NPs) is biologically safe, cost-effective, and environment-friendly, and is becoming more attractive in various fields: the food industry, biotechnology, materials science, pharmaceuticals, and cosmeceuticals. Kombucha culture (named SCOBY—Symbiotic Culture of Bacteria and Yeasts) is a wild consortium of microorganisms naturally immobilized in a nanocellulose membrane. In this study, SCOBY-based membranes decorated with gold NPs (AuNPs) or silver NPs (AgNPs) were produced through an eco-friendly process. In the first stage, the microbial consortium immobilized in a nanocellulose membrane was grown by the fermentation of a black tea-based medium. AgNP and AuNP deposition on the SCOBY nanocellulose membrane (SNM) was achieved using only the washed, dried, and finely ground SNM and metal precursors. The biosynthesized AuNPs/SNM and AgNPs/SNM were characterized by Scanning Electron Microscopy (SEM) coupled with Energy-Dispersive Spectroscopy (EDS), X-ray diffraction (XRD), and Fourier-Transform Infrared (FTIR) Spectroscopy. SEM images show cellulose fibrils and the successful incorporation of Ag nanoparticles with an average size of 50 nm and Au nanoparticles (30 nm) into SNM. In XRD, the characteristic diffractograms of Iα and Iβ cellulose allomorphs appear and the representative patterns confirm the formation of AgNPs and AuNPs. The antimicrobial potential of the SNM enriched with nanoparticles was evaluated by the well-diffusion technique against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus. The metal-decorated SNM showed good antimicrobial potential, and the results highlight the increased antimicrobial performance of AuNPs/SNM and AgNPs/SNM compared to raw SNM. The results recommend Ag-decorated SNM (Ag-SNMs) and Au-decorated SNM (Au-SNMs) for multiple practical applications such as medical and food packaging fields. The antioxidant effect was determined by DPPH and ABTS tests. In the DPPH assay, the Au-NPs and Ag-NPs showed a higher antioxidant activity.

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BIOCOMPATIBLE BIODEGRADABLE MATERIALS BASED ON CHITOSAN MODIFIED WITH NANOSTRUCTURED TITANIUM DIOXIDE
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In light of current trends to reduce the ecological load, much attention is being paid to biopolymer-based materials - from the development of biomedical drugs, membranes for purification and packaging materials. Large-scale research in this direction is carried out using chitosan (CTS) due to its biocompatibility, biodegradability, and antimicrobial properties. The CTS limiting factor is its low physical-mechanical characteristics and thermal stability. The actual task is CTS modification by combining it with materials that are also biocompatible and non-toxic. One of the promising compounds is TiO2, which has a pronounced antimicrobial and photocatalytic activity. At the same time, the strengthening of useful properties of the composite material should be expected when TiO2 in nanostructured form is used.

The research aims to obtain CTS based materials modified with TiO2 nanoparticles (NPs); and study their biodegradation, physical-mechanical, thermal-physical and antibacterial properties. TiO2 NPs with average sizes ranging from 20 to 920 nm were prepared from Ti(OPri)4 by sol-gel technology. TiO2 NPs were incorporated into solutions of 3 wt.% CTS in acetic acid. The TiO2 concentration was varied from 0.5 to 10 wt.% (relative to CTS mass), acetic acid - from 1.2 to 6 wt.%. Transparent homogeneous materials with high physical-mechanical properties were obtained. The highest tensile strength and deformation - up to 100 MPa and 30% - are possessed by films containing up to 2 wt.% of TiO2 (< 50 nm). The effect decreases when the TiO2 NPs size and concentration increase. Thermal-physical characteristics of CTS with 2 wt.% of TiO2 NPs were studied by differential scanning calorimetry and dynamic mechanical analysis methods. It was found that the materials are degraded by Aspergillus niger by 50% within 4 weeks and exhibit antibacterial activity against Staphylococcus Aureus.

The work was financially supported by the Russian Science Foundation (project No. 23-74-10069).

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Investigation of Gelatin-Based Nanofibers for Tissue Regeneration: Degradation and Water Absorption Properties

Nanofibers exhibit considerable potential as materials for tissue regeneration, owing to their adjustable characteristics and compatibility with biological systems. In the present investigation, nanofibers were prepared by dissolving 27% gelatin in a solvent combination consisting of 70% acetic acid (AcA) and 9% dimethyl sulfoxide (DMSO) in a ratio of 95:5. After that, the obtained gelatin scaffolds were crosslinked with 25% glutaraldehyde (GA) due to the poor mechanical properties of gelatin in a physiological environment.

The nanofiber's water absorption capacity and degradation rate were assessed to determine its suitability for prospective application in the field of wound healing. The degradation rate of the nanofibers was monitored for a duration of 21 days, during which degradation rates were evaluated at regular intervals of 7 days. Furthermore, an assessment of the capacity for water uptake was conducted for a duration of 7 days. The results showed that the degradation rate increased from 34.27% after 7 days to 74.39% by day 21, showing a progressive process of disintegration. In addition, the nanofibers demonstrated a notable capacity for water absorption, with absorption rates peaking at 437.38% on the initial day and thereafter stabilizing at 286.43% over a period of 7 days. The results of this study highlight the promise of crosslinked gelatin-based nanofibers as a viable option for tissue engineering purposes, specifically in the context of wound healing. This is due to their ability to exhibit controlled degradation and high water absorption, which are highly favorable characteristics. Additional research is necessary to examine the biocompatibility and in vivo performance of nanofibers to confirm their effectiveness and safety for use in clinical applications.

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Development of Galatite-Eggshell membranes and bioactive glass scaffolds for their use in bone tissue engineering

Treatment of large bone defects is one of the most challenging tasks in orthopedics, an estimated of 2.2 million bone grafting procedures are performed worldwide per year. Bone tissue engineering has an increasing interest in the development and construction of analogous bone grafts with osteoconductive, bioactive, biodegradation, and mechanical properties. Bioactive glasses (BG) are being utilized as biocompatible, biodegradable materials and collagen (Col) represents more than 90 % of the bone organic matrix, both materials have shown excellent properties in bone repair. The galatite is frequently named artificial bone and is a thermostable polymer obtained with casein-formaldehyde.

The current study involves the fabrication of novel 3D scaffolds conformed by galatite (Gal) obtained from goat milk-casein, bioactive glass (BG) synthesized by sol-gel technique, and as a source of collagen (Col), they were used eggshell inner membranes. Scaffolds were elaborated by the solvent-casting technique and each phase was characterized by FTIR, XRD, and SEM evaluations; also bioactivity and biodegradability of the composites were in-vitro evaluated by immersion into simulated body fluid (SBF) and phosphate-buffered saline solution (PBS). Mechanical characterization under compression forces was taken in the CellScale Univert (R) equipment to observe the strain-stress curves. Obtained results, make the materials valuable in various biomedical applications, including bone tissue engineering, drug delivery systems, and implants.

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