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.

Despite their broad biomedical applications in orthopedics and dentistry, metallic implants are still associated with failures due to their lack of surface biofunctionality, leading to prosthesis-related microbial infections. In order to address this issue, the current study focuses on the fabrication and characterization of a novel type of antibacterial coating based on gallium (III)-chitosan (Ga (III)-CS) complex layers deposited on metallic substrates via electrophoretic deposition (EPD). Aiming for the production of homogeneous and monophasic coatings, a two step-procedure was applied: the first step involved the synthesis of the Ga (III)-CS complex, followed by EPD from suitable solutions in an acetic acid–aqueous solvent. The influence of Ga (III) concentration on the stability of the suspensions was evaluated in terms of zeta potential. Fourier transform infrared (FTIR) and energy dispersive X-ray (EDX) spectroscopic analyses indicated the chelation of CS with Ga (III) within the coatings, while scanning electron microscopy (SEM) confirmed that no additional metallic gallium deposited during EPD. Furthermore, the results demonstrated that the wettability, mechanical properties, swelling ability, and enzymatic degradation of the coatings were affected by the quantity of Ga (III) ions. Colony forming unit (CFU) tests showed a strong synergistic effect between CS and Ga (III) in inhibiting Escherichia coli strain growth compared to control CS samples. An in vitro study with MG-63 cells showed that Ga (III)-containing coatings were not toxic after 24 h of incubation.

Zein coatings were obtained by electrophoretic deposition (EPD) on commercially pure titanium substrates in an as-received state and after various chemical treatments. The properties of the zein solution, zeta potential and conductivity, at varying pH values were investigated. It was found that the zein content and the ratio of water to ethanol of the solution used for EPD, as well as the process voltage value and time, significantly influence the morphology of coatings. The deposits obtained from the solution containing 150 g/L and 200 g/L of zein and 10 vol % of water and 90 vol % of ethanol, about 4–5 μm thick, were dense and homogeneous. The effect of chemical treatment of the Ti substrate surface prior to EPD on coating adhesion to the substrate was determined. The coatings showed the highest adhesion to the as-received and anodized substrates due to the presence of a thick TiO₂ layer on their surfaces and the presence of specific surface features. Coated titanium substrates showed slightly lower electrochemical corrosion resistance than the uncoated one in Ringer’s solution. The coatings showed a well-developed surface topography compared to the as-received substrate, and they demonstrated hydrophilic nature. The present results provide new insights for the further development of zein-based composite coatings for biomedical engineering applications.

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.

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.