The rate of human mortality from infectious diseases caused by antibiotic-resistant bacteria is a major public concern. Currently, the search for new strategies to treat infections and overcome antimicrobial resistance is a challenge. Nanoparticles (NPs) offer an alternative approach to biocide design that involves antibacterial mechanisms other than antibiotics. The attention is primarily attracted due to the large surface area, diverse physical and chemical properties, variety of precursor materials, and the ability to form hybrid structures. Of particular interest are metal and metal oxide NPs that can survive in harsh conditions without losing their colloidal stability. They provide long-term antibacterial activity and can destroy bacterial biofilms. This review summarizes and discusses recent progress in understanding the antibacterial mechanisms of metal/metal oxide NPs, highlighting three key aspects: physical interaction with the cell wall, release of metal ions, and the generation of reactive oxygen species (ROS). Unlike antibiotics with a single mode of action, NPs can simultaneously exhibit multiple mechanisms with a synergistic effect. This leads to the destruction of cell membranes, damage to DNAs and proteins, inactivation of enzymes, oxidation of cellular components, and ultimately, cell death. The activity of NPs against bacterial biofilms is also considered. In addition, this review focuses on the current state of the most widely used metal-containing NPs with a comprehensive discussion of the specific mechanisms for each type (Ag, Au, Cu/CuO, TiO2, ZnO, Fe2O3/Fe3O4). Finally, the review discusses approaches to enhancing the biocidal efficacy of NPs through modification and composite formation, as well as the use of light and magnetic field.

Photocrosslinkable hydrogels based on hyaluronic acid are promising biomaterials high in demand in tissue engineering. Typically, hydrogels are photocured under the action of UV or blue light strongly absorbed by biotissues, which limits prototyping under living organism conditions. To overcome this limitation, we propose the derivatives of well-known photosensitizers, namely chlorin p6, chlorin e6 and phthalocyanine, as those for radical polymerization in the transparency window of biotissues. Taking into account the efficiency of radical generation and dark and light cell toxicity, we evaluated water miscible pyridine phthalocyanine as a promising initiator for the intravital hydrogel photoprinting of hyaluronic acid glycidyl methacrylate (HAGM) under irradiation near 670 nm. Coinitiators (dithiothreitol or 2-mercaptoethanol) reduce the irradiation dose required for HAGM crosslinking from similar to 405 J cm-2 to 80 J cm-2. Patterning by direct laser writing using a scanning 675 nm laser beam was performed to demonstrate the formation of complex shape structures. Young's moduli typical of soft tissue (similar to 270-460 kPa) were achieved for crosslinked hydrogels. The viability of human keratinocytes HaCaT cells within the photocrosslinking process was shown. To demonstrate scaffolding across the biotissue barrier, the subcutaneously injected photocomposition was crosslinked in BALB/c mice. The safety of the irradiation dose of 660-675 nm light (100 mW cm-2, 15 min) and the non-toxicity of the hydrogel components were confirmed by histomorphologic analysis. The intravitally photocrosslinked scaffolds maintained their shape and size for at least one month, accompanied by slow biodegradation. We conclude that the proposed technology provides a lucrative opportunity for minimally invasive scaffold formation through biotissue barriers.

Maxillofacial defects, arising from trauma, oncological disease or congenital abnormalities, detrimentally affect daily life. Prosthetic repair offers the aesthetic and functional reconstruction with the help of materials mimicking natural tissues. 3D polymer printing enables the design of patient-specific prostheses with high structural complexity, as well as rapid and low-cost fabrication on-demand. However, 3D printing for prosthetics is still in the early stage of development and faces various challenges for widespread use. This is because the most suitable polymers for maxillofacial restoration are soft materials that do not have the required printability, mechanical strength of the printed parts, as well as functionality. This review focuses on the challenges and opportunities of 3D printing techniques for production of polymer maxillofacial prostheses using computer-aided design and modeling software. Review discusses the widely used polymers, as well as their blends and composites, which meet the most important assessment criteria, such as the physicochemical, biological, aesthetic properties and processability in 3D printing. In addition, strategies for improving the polymer properties, such as their printability, mechanical strength, and their ability to print multimaterial and architectural structures are highlighted. The current state of the prosthetic retention system is presented with a focus on actively used polymer adhesives and the recently implemented prosthesis-supporting osseointegrated implants, with an emphasis on their creation from 3D-printed polymers. The successful prosthetics is discussed in terms of the specificity of polymer materials at the restoration site. The approaches and technological prospects are also explored through the examples of the nasal, auricle and ocular prostheses, ranging from prototypes to end-use products.

The progress in the field of tissue engineering is largely driven by the development of 3D laser printing technologies, which allow precise creation of hydrogel scaffolds containing cells (the so-called tissue-engineered constructs), using photoinduced radical reactions of polymerization and crosslinking. The review considers the main mechanisms and features of such reactions, presents the most common materials for photocompositions, including natural and synthetic polymers and precursors, and describes various mechanisms for photoinitiator activation. Advances in the field of photopolymerization enable application of modern laser 3D printing techniques based on extrusion and stereolithography to design tissueengineered constructs in a wide range of sizes and shapes with a finely organized architecture. The integration of such methods with the methods of bioengineering and cell technology is discussed, including for the creation of tissue-specific and in vivo polymerized constructs. The bibliography includes 225 references.

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.

Biocompatible hydrogels have gained much attention in tissue engineering, preferably as scaffolds providing the cell attachment and viability in the hydrogel bulk. This requires fabrication of the hydrogels with pores, the sizes of which are in the range of 100-300 mu m, most optimal for cell growth. The composition of hydrogels or method of fabrication may affect the formation of porous structure. We prepared hydrogels via photoinduced crosslinking of hyaluronic acid modified with glycidyl methacrylate under irradiation at different wavelengths using two photoinitiators. The hydrogel structure was varied by blending hyaluronic acid derivative with other modified polymers of natural origin (gelatin and pullulan) with grafted vinyl moieties or using filler (sucrose). The most optimal pore sizes for cell growth were obtained for hydrogels derived from modified hyaluronic acid, with the addition of sucrose or processed with the single freeze-thaw cycle. The produced hydrogels demonstrated lack of with HaCaT cells inside bulk.

Upconversion nanoparticle (UCNP)-driven polymerization attracts great attention due to the ability of near-infrared light to penetrate deeper into biological media and synthetic materials than ultraviolet or visible light. Despite significant progress, the limitation of near-infrared light-triggered polymerization is associated with a key element of the photocurable composition, a UCNP/photoinitiator complex or a nanoinitiator. To determine the impact of resonance energy transfer from UCNPs to photoinitiator (PI) and its effect on polymerization, we developed two different photocurable compositions consisting of the polyethylene glycol diacrylate (PEG-DA), ultraviolet- and blue-emitting NaYF4: Yb3+, Tm3+ UCNPs with hydrophobic surface combined with water-soluble or insoluble PI. We found that transfer energy in these nanoinitiators proceeds differently: in UCNP/water-soluble PI (lithium phenyl-2,4,6-trimethylbenzoylphosphinate or LAP), it occurs through the photon-mediated transfer while in UCNP/water-insoluble PI (2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone or Irgacure 369), it takes place via the non-radiative resonant energy transfer. The impact of these processes in homolytic decomposition of initiator is extremely important in terms of the precisely controlled fabrication of polymer structures. PEG-DA facilitates the affinity between hydrophilic and hydrophobic components of the photocurable composition, which provides UCNP-driven cross-linking of biopolymers such as methacrylated hyaluronic acid and gelatin. 3D structures were prototyped to demonstrate the one-step rapid procedure of nanoinitiator preparation and emphasize the control of the energy transfer in UCNP/PI complexes for further development of UCNP-driven polymerization.

Protein nanoparticles (NPs) based on endogenous biopolymers are promising platform for bioimaging and advanced therapy since they are biocompatible, biodegradable and have low systematic toxicity with high loading capacity. In this work we studied albumin NPs loaded with three cyanine dyes: ICG, IR-806 and IR-820 for colloidal and optical properties. We demonstrated that cross-linked albumin nanoparticles functionalized with IR dyes were promising for optical bioimaging in biotissue transparency window (700-1700 nm). The proposed dye-loaded NPs were of low toxicity in vitro and could be promising for in vivo applications.

As an alternative to antibiotics, antimicrobial photodynamic therapy method leads to the treatment on microorganisms and does not cause the development of resistance. This work demonstrates the use of flavin mononucleotide (FMN), which acts as a photosensitizer capable of generating singlet oxygen and other reactive oxygen species, that have a phototoxic effect to bacteria. The effectiveness of its action increases in the case of the use of silver nano particles with antibacterial activity. This study presents the development of approaches for the controlled increase in the effectiveness of antimicrobial photodynamic therapy using FMN-silver nanoparticle complexes. The formation of the complex is accompanied by the generation of radicals upon 365 nm irradiation, that has extreme dependence and also leads to a change in the fluorescence kinetics. The introduction of triethanolamine activator to FMN into the system leads to the generation of radicals. The method of synthesis of silver nanoparticles also significantly affects the optical properties of the formed complex.

The formation of complexes and crystals of bacterial nucleoid DNA inside bacterial cells in response to adverse external influences is of great interest both in biophysics and structural biology, and in various fields of industry. The main role in the condensation and crystallization of DNA in bacteria under stressful conditions (starvation, temperature, oxidative, and other types of stress) is played by DNA-binding proteins DPS. In this work, the dynamic behavior and structure of Escherichia coli DPS protein complexes in solution with short-chain DNA (25 base pairs) are studied using classical molecular dynamics in the all-atom approximation with a change in the concentration of the phenolic lipid 4-hexylresorcinol, which is a chemical analog of bacterial anabiosis inducers. The effect of changing the concentration of 4-hexylresorcinol from 0 to 50, 100 and 500 molecules on the DNA-DPS complex is being studied. By searching for the linear interaction energy, data were obtained on the free energies of DNA-protein binding without and in the presence of 4-hexylresorcinol. It has been shown that high concentrations of 4-hexylresorcinol promote the formation of DNA complexes with DPS. To identify the features of the dynamic behavior of DNA and protein, the principal component analysis was carried out. The spatial and energy characteristics of the complexes was obtained.

Wide application of chitosan in modern technologies is limited by the lack of reliable and low-cost techniques to prepare size-tuned constructs with a complex surface morphology, improved optical and mechanical properties. We report a new simple method for preparation of transparent thermoreversible chitosan alcogels from chitosan/H2O/ethanol ternary systems. This method, termed "low temperature thermally induced phase separation under non-freezing conditions" (LT-TIPS-NF), fine tunes gelation by adjusting only temperature (from 5 to -25 °C) and varying the initial content of chitosan (from 0.5 to 2.0 wt%) and ethanol (from 28.5 to 47.5 vol%). Transparent non-swelling final constructs of complex shape are prepared by fixing the pre-formed alcogels with a base solution. The size of the gel constructs is limited only by the dimensions of the mold and the cooling chamber. The LT-TIPS-NF is applicable both in injection molding and 3D printing techniques. The in vitro and in vivo experiments show the absence of prominent cytotoxicity and well-defined cell adhesion on the obtained hydrogels. Thus, this facile and scalable technique provides the multifunctional chitosan gel preparation with easily controlled properties exploiting inexpensive, renewable, and environmentally friendly source polysaccharide. These materials have prospects for a variety of uses, especially for biomedical applications.

Технология 3D-печати стала ключевой движущей силой в изменении парадигмы производственного процесса в различных отраслях промышленности. Новой вехой в 3D-печати может стать технология инфракрасной полимеризации, основанная на достижениях в области синтеза наноматериалов, способных эффективно преобразовывать излучение ближнего ИК-диапазона спектра в УФ-свет. Эта инновационная технология может проложить путь к разработке множества решений в промышленности и предвещает новые рубежи для фотоники, оптоэлектроники и биомедицины. В обзоре представлено краткое обобщение имеющихся достижений, а также ограничения, сдерживающие развитие технологии ИК-фотополимеризации.

Materials based on hyaluronic acid (HA) are extensively used in tissue engineering as scaffolds. Photoinduced crosslinking is one way to prepare them, and, for this, HA must be modified with vinyl groups, which are capable of participating in free-radical reactions upon exposure to light. The quantity of grafted vinyl groups, represented as the degree of substitution (DS), is an important parameter of modified HA (mHA) that is related to the mechanical, chemical, and biological properties of scaffolds. Here, we demonstrate the feasibility of tuning DS by varying the reaction parameters (composition and concentration of reaction components and reaction conditions) and investigate the effect of DS on the viscosity of mHA solutions. As example, we consider the photoinduced reaction of mHA in the presence of flavin mononucleotide as the initiator, which can be used in fabrication of noncytotoxic scaffolds by 3D printing. The growth behavior of fibroblasts on the scaffold surface is studied.

One-dimensional (1D) necklace-like assembly of inorganic nanoparticles exhibits unique collective properties, which are critical to open up new and remarkable opportunities in the field of nanotechnology. This review focuses on the recent advances in the production of these types of assemblies employing two strategies: colloidal synthesis and self-assembly procedures. After a brief description of the forces guiding nanoparticles towards the assembly, the main features of both strategies are discussed. Examples of approaches, typically involved in colloidal synthesis, are highlighted. The peculiar properties of 1D nanostructures are strictly associated with the nanoparticle arrangement in the form of highly ordered assemblies, which are attained during the synthesis both in the solution and using a template, as well as under the action of an external force. The various 1D necklace-like structures, created through nanoparticle self-assembly, demonstrate aligned, oriented nanoparticle organization. Diverse nature, size and shape of preformed particles as building blocks, along with utilizing different linkers, templates or external field lead to fabrication of 1D chain nanostructures with properties responsible for their wide applications. The unique structure-property relationship, both in colloidal synthesis, and self-assembly, offers broad spectrum of 1D necklace-like nanostructure implementations, illustrated by their use in photonics, electronics, electrocatalysis, magnetics.

Formulation of promising anticancer herbal drug curcumin as a nanoscale-sized curcumin (nanocurcumin) improved its delivery to cells and organisms both in vitro and in vivo. We report on coupling nanocurcumin with upconversion nanoparticles (UCNPs) using Poly (lactic-co-glycolic Acid) (PLGA) to endow visualisation in the near-infrared transparency window. Nanocurcumin was prepared by solvent-antisolvent method. NaYF4:Yb,Er (UCNP1) and NaYF4:Yb,Tm (UCNP2) nanoparticles were synthesised by reverse microemulsion method and then functionalized it with PLGA to form UCNP-PLGA nanocarrier followed up by loading with the solvent-antisolvent process synthesized herbal nanocurcumin. The UCNP samples were extensively characterised with XRD, Raman, FTIR, DSC, TGA, UV-VIS-NIR spectrophotometer, Upconversion spectrofluorometer, HRSEM, EDAX and Zeta Potential analyses. UCNP1-PLGA-nanocurcumin exhibited emission at 520, 540, 660 nm and UCNP2-PLGA-nanocurmin showed emission at 480 and 800 nm spectral bands. UCNP-PLGA-nanocurcumin incubated with rat glioblastoma cells demonstrated moderate cytotoxicity, 60–80% cell viability at 0.12–0.02 mg/mL marginally suitable for therapeutic applications. The cytotoxicity of UCNPs evaluated in tumour spheroids models confirmed UCNP-PLGA-nanocurcumin therapeutic potential. As-synthesised curcumin-loaded nanocomplexes were administered in tumour-bearing laboratory animals (Lewis lung cancer model) and showed adequate contrast to enable in vivo and ex vivo study of UCNP-PLGA-nanocurcumin bio distribution in organs, with dominant distribution in the liver and lungs. Our studies demonstrate promise of nanocurcumin-loaded upconversion nanoparticles for theranostics applications.

Bioprinting emerges as a powerful flexible approach for tissue engineering with prospective capability to produce tissue on demand, including biomimetic hollow-core fiber structures. In spite of significance for tissue engineering, hollow-core structures proved difficult to fabricate, with the existing methods limited to multistage, time-consuming, and cumbersome procedures. Here, we report a versatile cell-friendly photopolymerization approach that enables single-step prototyping of hollow-core as well as solid-core hydrogel fibers initially loaded with living cells. This approach was implemented by extruding cell-laden hyaluronic acid glycidyl methacrylate hydrogel directly into aqueous solution containing free radicals generated by continuous blue light photoexcitation of the flavin mononucleotide/triethanolamine photoinitiator. Diffusion of free radicals from the solution to the extruded structure initiated cross-linking of the hydrogel, progressing from the structure surface inwards. Thus, the cross-linked wall is formed and its thickness is limited by penetration of free radicals in the hydrogel volume. After developing in water, the hollow-core fiber is formed with centimeter range of lengths. Amazingly, HaCaT cells embedded in the hydrogel successfully go through the fabrication procedure. The broad size ranges have been demonstrated: from solid core to 6% wall thickness of the outer diameter, which was variable from sub-millimeter to 6 mm, and Young's modulus ∼1.6 ± 0.4 MPa. This new proof-of-concept fibers photofabrication approach opens lucrative opportunities for facile three-dimensional fabrication of hollow-core biostructures with controllable geometry.

A unified analytical technology based on the integration of scanning probe nanotomography and optical microscopy (SPNT–OM) is presented, and the potential of the technology is demonstrated by the example of a multiparameter analysis of encoded microspheres. The presented SPNT–OM technology can become a powerful tool for multimodal nanocharacterization of a wide range of microparticles, composites, and hybrid polymers.