Zoya Hadzhieva

Pathogenic air and water contaminations present major health issues nowadays. Filter-based protective devices have been commonly utilized to capture airborne or waterborne microorganisms and viruses in order to reduce or inhibit the transmission of infectious diseases. Some approaches to extend the functionality of filtering devices and to further enhance their capability to inactive pathogens include the application of antimicrobial coatings on the filter surface. In this regard, the current work aims to develop innovative coatings with antiviral and antibacterial properties composed of a chitosan matrix incorporating bioactive glass (BG) nanoparticles or silver nitrate (AgNO₃) on metallic filters by using electrophoretic deposition. The so-produced chitosan/BG- and chitosan/AgNO₃-coated filters were characterized in terms of their morphology, chemical composition, filtering capability, antibacterial properties against Staphylococcus aureus, and antiviral activity against coronavirus OC43, rhinovirus, adenovirus, and influenza virus. The results confirmed that chitosan/AgNO₃ and chitosan/BG coatings exhibited no blockage of the filter pores. The bubble point values for both coating types were similar to the measurements of uncoated filters, suggesting intact filtration capability after the application of the coatings. The antibacterial assay showed the antibacterial activity of >99% for both chitosan/AgNO₃ and chitosan/BG coatings against S. aureus. Finally, chitosan/AgNO₃-coated filters showed antiviral activity against three out of the four tested viruses (HCoV-OC43, HRV-A1, and IFV-AH3N2) and exerted a partial antiviral action against AdV-5. On the other hand, chitosan/BG-coated filters were active against all tested respiratory viruses. The outcomes of this study evidenced that the developed multimaterial coatings could serve as a suitable platform to produce antimicrobial filtering systems for a broad-spectrum application.

The application of divalent bioactive metal ions, such as Cu²⁺, Zn²⁺, and Mn²⁺, emerges as a growth factor-free approach for bone defect regeneration. Delivery of those ions can be achieved by organic or inorganic phases through desirable rapid or sustainable release in order to stimulate specific cell responses. In this work, bioactive ions were incorporated into both phases, chitosan (Cht), via chelation reactions, and mesoporous bioactive glass nanoparticles (MBGNs), by doping. The BG/Cht composites with undoped and Cu-, Zn-, or Mn-doped MBGNs were produced as spherical microparticles with a narrow size distribution and an average size of 42-45 μm via electrohydrodynamic atomization. Swelling studies showed enhanced water uptake in the complete cell culture medium with values between 2.5 and 3.1 compared to phosphate-buffered saline (2.2-2.5). Ion release experiments in phosphate-buffered saline revealed a pronounced release of silicon and calcium up to 7 days for all samples. A sustained release of manganese ions from the MnBG/Cht sample was detected for up to 14 days. A precipitated layer of calcium phosphates on all composites, except on the MnBG/Cht samples, confirmed the materials' bioactivity after 21 days in simulated body fluid. Indirect cytotoxicity tests indicated that the materials were generally nontoxic to human osteosarcoma (MG-63) cells at concentrations below 1 mg/mL. However, direct contact assays with MG-63 and human dermal fibroblast (HDFa) cells revealed concentration-dependent cytotoxic effects, particularly for MnBG/Cht microparticles at a concentration of 0.5 mg/mL. Vascular endothelial growth factor (VEGF) expression analysis on MG-63 and HDFa cells demonstrated that only a higher concentration of MnBG/Cht significantly enhanced the angiogenic response in MG-63 cells, likely due to the decreased cell viability and oxidative stress generated by the redox activity of Mn²⁺ ions. Our results show that composite microparticles have good potential in the design of microparticulate systems with tailored properties through the combination of bioactive metal ions.

Increased demand for advanced biomaterials in tissue engineering has driven research to develop innovative solutions based on smart material combinations. Mesoporous bioactive glass nanoparticles (MBGNs) have emerged as attractive materials because of their angiogenic and regenerative properties. This study explores the incorporation of boron-doped mesoporous bioactive glass nanoparticles (B-MBGNs) into poly(ε-caprolactone) (PCL) and poly(propylene succinate-co-glycerol succinate) (PPSG) fibers to enhance their biodegradation and bioactivity. B-MBGNs were synthesized via a microemulsion-assisted sol-gel method and characterized through morphology, pore size distribution, composition, and surface area. PCL/PPSG nanofibers were fabricated using an alternative combination of solvents, formic acid, and acetic acid. B-MBGNs were incorporated into PCL/PPSG solutions at concentrations of 5, 10, and 15 wt % and electrospun into nanofiber mats under a flow rate of 0.2 mL/h at 22 °C and 40% relative humidity, while the voltage applied at the needle tip was 18 kV and -2 kV at the rotating drum. The addition of 10 wt % of B-MBGNs resulted in nanofibers that exhibited a high degradation rate in PBS with a weight loss of 44% in 30 days, significant hydrophilicity with a contact angle of 33°, and improvements in cell viability tested with normal human dermal fibroblasts (NHDF). In addition, the study highlights the effect of the concentration of B-MBGNs on the morphology of the fibers, which can agglomerate and form undesired beads. Although the particles improved cellular activity, the changes in morphology caused tension points that reduced the elasticity of the fibers. Overall, this work contributes to the innovative use of green polyesters combined with boron ions in electrospun fibrous scaffolds, expanding the opportunities for applications in tissue regeneration, for example, to treat chronic wounds in diabetic patients.

To be able to support the complex process of wound closure, a biocompatible material is required that combines suitable adhesiveness and stability with the ability to withstand certain biological challenges such as biofouling while avoiding undesired side effects i.e., hemolysis. Here, we present an asymmetrically designed, cellulose-based bilayer film that satisfies all those requirements and can be produced in a simple and environmentally friendly manner. The wound-facing side of this film features excellent adhesive properties brought about by a biocompatible catechol functionalization of carboxymethyl cellulose and promotes blood coagulation while avoiding hemolysis. In contrast, the outer side of the film has bacteria-repellent properties, which are established by the anti-bacterial glycoprotein mucin, integrated into a fibrous cellulose matrix, that can be covalently crosslinked. In addition, the construct can act as a drug reservoir and decomposes in a wet environment. These properties render the bilayer film a promising candidate for applications in wound closure, particularly for lesions encountered in intestinal or ocular tissues.

Peri-implant infection is rapidly becoming an – if not the most – important clinical challenge for indwelling medical devices. To alleviate the global rise in antibiotic use for the treatment of such infections, a plethora of biomaterials/bioengineering-based antimicrobial strategies are emerging to restrict or ideally to eliminate microbial adhesion and biofilm formation on implant surfaces. Yet, the development of such approaches faces specific challenges, like biocompatibility concerns, reduced antimicrobial effectiveness, long-term stability issues and antibiotic resistance development, which limit translation to the clinic. This review provides insights into the antimicrobial activity of current state-of-the-art biomaterial-based approaches to address the aforementioned issues. Translational research strategies and regulatory framework are also emphasised as key elements facilitating clinical implementation of anti-infective biomaterials. This review closes with the vision that the integration of computational tools and experimental databases using artificial intelligence (AI) would provide new insights for the accelerated development of next-generation biomaterial-based antimicrobial strategies.

Cu- and Mg-doped mesoporous sol-gel bioactive glasses (MSGG) were developed and their microstructure was investigated. Selected biological tests were also performed to assess their suitability for the functionalization of polymer zein coatings. The electrophoretic deposition (EPD) conditions to obtain composite coatings on Ti-13Nb-13Zr substrates were determined. The coatings with excellent adhesion to the substrates were macroscopically uniform, exhibiting open porosity and high roughness. The surfaces of the samples coated with MSGG/zein coatings became more hydrophilic than the titanium alloy substrates. However, with increase of the volume fraction of glass particles in the coatings, the contact angle increased. The coated alloy showed enhanced resistance to electrochemical corrosion in Ringer’s solution. The chemical composition of the glass used in the coating affected the parameters of wettability and resistance to electrochemical corrosion. Both coating types showed an increase in the antibacterial properties against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria compared to pure zein. However, no significant differences were observed after a 24 h-long test.

Tumor recurrence is a major problem during the treatment of giant cell tumors of bone (GCTB). We recently identified tumor cell-specific cytotoxic effects of bioactive glasses (BGs) toward neoplastic stromal cells derived from GCTB tissue (GCTSCs) in vitro. Since these data indicated a promising role of BGs in the adjuvant treatment of GCTBs, we aimed to investigate the transferability of the in vitro data into the more complex in vivo situation in the current study. We first analyzed the cytotoxicity of three different BGs in vitro by WST-1 assay after co-cultivation with primary GCTSC cell lines. The effects of BGs on tumor engraftment and growth were analyzed by chicken chorioallantoic membrane (CAM) assays and subsequent quantification of tumor take rates and tumor volumes. In vitro, all tested BGs displayed a cytotoxic effect on GCTSCs that was dependent on BG composition, concentration, and particle size. Comparable effects could be observed within the in vivo environment resulting in reduced tumor take rates and tumor volumes in BG-treated samples. These data indicate a possible clinical application of BGs in the context of GCTB therapy, mediating a reduction of recurrence rates with the simultaneous promotion of bone regeneration.

Even though antibiotic treatment remains one of the most common tools to handle bacterial infections, the excessive antibiotic concentration at the target site may lead to undesired effects. Aiming at the fabrication of antibiotic-free biomaterials for antibacterial applications, in this work, we propose the synthesis of gallium (III)—chitosan (Ga (III)-CS) complexes with six different gallium concentrations via an in situ precipitation method. Fourier Transform infrared spectroscopy indicated the chelation of chitosan with Ga (III) by peak shifts and changes in the relative absorbance of key spectral bands, while energy-dispersive X-ray spectroscopy indicated the homogenous distribution of the metal ions within the polymer matrix. Additionally, similar to CS, all Ga (III)-CS complexes showed hydrophobic behavior during static contact-angle measurements. The antibacterial property of the complexes against both Gram-negative and Gram-positive bacteria was positively correlated with the Ga (III) concentration. Moreover, cell studies confirmed the nontoxic behavior of the complexes against the human osteosarcoma cell line (MG-63 cells) and mouse embryonic fibroblasts cell line (MEFs). Based on the results of this study, new antibiotic-free antibacterial biomaterials based on Ga (III)-CS can be developed, expanding the scope of CS applications in the biomedical field.