The purpose of this work is to establish the influence of the nature of solid alginate gels (alginic acid, AAG; calcium alginate, CAG) and the conditions of methylene blue (MB) introduction to alginate matrices upon its release into aqueous media. MB is an active photosensitizer, which is used in the photodynamic therapy of tumors and purulent wounds. Solid alginate gels based on AAG and CAG were obtained by adding hydrochloric acid and calcium chloride to sodium alginate. The dye was introduced into the matrix either at the stage of gelation or by immersing the gel in an aqueous solution of the dye. It has been shown that the strength of the dye’s attachment to AAG is higher than that of CAG, which leads to a higher rate of MB release from CAG into aqueous media. It has also been shown that, when introduced at the stage of gel formation, MB is released into both the water and buffer solutions. When MB is introduced by gel immersion into an MB solution, the dye may be released only into salt solutions. An alginate gel with immobilized MB can be used as a solid photosensitizing system with the controlled release of the photoactive agent into the wound cavity for photodynamic treatment.

В современной регенеративной медицине существует тенденция к переходу от металлических и керамических имплантируемых конструкций к биорезорбируемым полимерным имплантам, постепенно замещающимся собственными тканями организма. Интересным преимуществом таких полимерных конструкций является возможность их наполнения биологически активными веществами, высвобождающимися по мере деструкции матрицы, так что имплант становится пролонгированным источником препарата, оказывающего точечное локальное воздействие.

The influence of amphiphilic polymers (APs): poly-N-vinylpyrrolidone, polyethylene glycol and pluronics F127, F108, as well as sodium alginate (SA) on the activity of methylene blue (MB) in the photogeneration of singlet oxygen 1 О 2 , specifically, in a model photooxidation reaction of tryptophan in water was studied. It was shown that in the presence of all the above-mentioned AP, an increase in the effective rate constant ( k eff ) of tryptophan photooxidation is observed. It was suggested that the observed effect is associated with the interaction of MB with APs, which leads to disaggregation of dye associates. Such disaggregation leads to an increase in the optical density and intensity of MB luminescence. It was also shown that the photocatalytic activity of MB decreases by a factor of 1.5–3.5 in the presence of SA, which is due to the ionic interaction of the cationic MB with polyanionic SA. The interaction of MB with polysaccharide is confirmed by changes in the absorption and fluorescence spectra of the dye. The introduction of APs into a solution containing MB and SA prevents the interaction between MB and polysaccharide, which leads to an increase in the k eff values of tryptophan photooxidation in the presence of MB-AP-SA system, as well as to an increase in the optical density and fluorescence intensity of MB when AP and SA are added. The existence of weak interactions between the hydrophobic groups of MB molecules and the AP (polyvinylpyrrolidone) is also evidenced by the data obtained through 1 H-NMR spectroscopy and the degree of MB fluorescence anisotropy. The AFM method shows the change in the surface structure of a thin film obtained by evaporating an aqueous solution of MB-F108-SA compared to the corresponding structure of a film obtained by evaporating an aqueous solution of MB-SA. MB-AP and MB-AP-SA systems may be promising for practical application in the aPDT treatment of chronic microbial superficial infections.

BackgroundThere is an urgent clinical need for targeted strategies aimed at the treatment of bone defects resulting from fractures, infections or tumors. 3D scaffolds represent an alternative to allogeneic MSC transplantation, due to their mimicry of the cell niche and the preservation of tissue structure. The actual structure of the scaffold itself can affect both effective cell adhesion and its osteoinductive properties. Currently, the effects of the structural heterogeneity of scaffolds on the behavior of cells and tissues at the site of damage have not been extensively studied.MethodsBoth homogeneous and heterogeneous scaffolds were generated from poly(L-lactic acid) methacrylated in supercritical carbon dioxide medium and were fabricated by two-photon polymerization. The homogeneous scaffolds consist of three layers of cylinders of the same diameter, whereas the heterogeneous (gradient pore sizes) scaffolds contain the middle layer of cylinders of increased diameter, imitating the native structure of spongy bone. To evaluate the osteoinductive properties of both types of scaffold, we performed in vitro and in vivo experiments. Multiphoton microscopy with fluorescence lifetime imaging microscopy was used for determining the metabolic states of MSCs, as a sensitive marker of cell differentiation. The results obtained from this approach were verified using standard markers of osteogenic differentiation and based on data from morphological analysis.ResultsThe heterogeneous scaffolds showed improved osteoinductive properties, accelerated the metabolic rearrangements associated with osteogenic differentiation, and enhanced the efficiency of bone tissue recovery, thereby providing for both the development of appropriate morphology and mineralization.ConclusionsThe authors suggest that the heterogeneous tissue constructs are a promising tool for the restoration of bone defects. And, furthermore, that our results demonstrate that the use of label-free bioimaging methods can be considered as an effective approach for intravital assessment of the efficiency of differentiation of MSCs on scaffolds.

The influence of chitosan (CS) and amphiphilic polymers (AP: pluronic F108 and polyvinylpyrrolidone (PVP)) on the photocatalytic activity of rose bengal (RB) in a model reaction of tryptophan photo-oxidation in phosphate-buffered saline (PBS) was studied. It was shown that in the presence of CS, the effective rate constant keff of tryptophan photo-oxidation catalyzed by RB in PBS solution decreases by a factor of two. This is due to the ionic interaction of the RB with the chitosan. Rose bengal in a slightly acidic environment (pH 4.5) passes into a neutral lactone form, which sharply reduces the photosensitizing properties of the dye. It was demonstrated that the introduction of AP into a solution containing RB and CS prevents direct interaction between RB and CS. This is evidenced by the presence of photocatalytic activity of the dye in the RB-AP-CS systems, as well as bathochromic shifts of the main absorption bands of the dye, and an increase in the optical density and luminescence intensity of the RB when AP is introduced into a buffer solution containing RB and chitosan. The presence of RB-CS and RB-AP interaction in aqueous and PBS media is confirmed by the increase in the degree of fluorescence anisotropy (r) of these binary systems. In an aqueous solution, the value of r for the RB-F108-CS system decreases by a factor of 3.5 (compared to the value of r for the RB-CS system), which is associated with the localization of the dye in pluronic micelles. In PBS, the fluorescence anisotropy is practically the same for all systems, which is related to the stability of the dye structure in this medium. The presence of interaction between RB and AP in aqueous solutions was confirmed by the proton NMR method. In addition, the formation of RB-F108 macromolecular complexes, which form associates during solution concentration (in particular, during evaporation), was shown by AFM. Such RB-AP-CS systems may be promising for practical application in the treatment of local foci of infections by aPDT.

Luminescent aerogels based on sodium alginate cross-linked with ions of rare earth elements (Eu3+, Tb3+, Sm3+) and containing phenanthroline, thenoyltrifluoroacetone, dibenzoylmethane, and acetylacetone as ligands introduced into the matrix during the impregnation of alginate aerogels (AEG), were obtained for the first time in a supercritical carbon dioxide medium. The impregnation method used made it possible to introduce organically soluble sensitizing ligands into polysaccharide matrices over the entire thickness of the sample while maintaining the porous structure of the aerogel. It is shown that the pore size and their specific area are 150 nm and 270 m2/g, respectively. Moreover, metal ions with content of about 23 wt.%, acting as cross-linking agents, are uniformly distributed over the thickness of the sample. In addition, the effect of sensitizing ligands on the luminescence intensity of cross-linked aerogel matrices is considered. The interaction in the resulting metal/ligand systems is unique for each pair, which is confirmed by the detection of broad bands with individual positions in the luminescence excitation spectra of photoactive aerogels.

A hydrophobic derivative of ciprofloxacin, hexanoylated ciprofloxacin (CPF-hex), has been used as a photoinitiator (PI) for two-photon polymerization (2PP) for the first time. We present, here, the synthesis of CPF-hex and its application for 2PP of methacrylate-terminated star-shaped poly (D,L-lactide), as well a systematic study on the optical, physicochemical and mechanical properties of the photocurable resin and prepared three-dimensional scaffolds. CPF-hex exhibited good solubility in the photocurable resin, high absorption at the two-photon wavelength and a low fluorescence quantum yield = 0.079. Structuring tests showed a relatively broad processing window and revealed the efficiency of CPF-hex as a 2PP PI. The prepared three-dimensional scaffolds showed good thermal stability; thermal decomposition was observed only at 314 °C. In addition, they demonstrated an increase in Young’s modulus after the UV post-curing (from 336 ± 79 MPa to 564 ± 183 MPa, which is close to those of a cancellous (trabecular) bone). Moreover, using CPF-hex as a 2PP PI did not compromise the scaffolds’ low cytotoxicity, thus they are suitable for potential application in bone tissue regeneration.

Polylactide was modified by the reaction of urethane formation in supercritical carbon dioxide, forming its methacrylate derivatives. Photopolymerization of the modified polylactides gave spatially cross-linked materials that can be used for the production of implants in regenerative medicine and tissue engineering.

Multi-ligand phosphor complexes of neodymium acetylacetonate with phenanthroline are synthesized in polymer matrices (oligourethane methacrylate, fluoroplast, polycarbonate) in supercritical carbon dioxide medium. At the same time the role of one of the ligands in such complexes is played by fragments of the polymer matrix. The luminescence spectra of the obtained ternary systems are described. It was shown that the position of the luminescence maxima is bathochromically shifted relative to the binary systems Nd(Acac)3/polymer obtained in a similar way and the magnitude of the shift depends on the nature of the polymer matrix. It was shown that upon the introduction of these components into polymers from a solution, similar phosphor mixed-ligand neodymium complexes do not form. The formation of new structures Nd(Acac)3/Phen/polymer upon impregnation of oligourethane methacrylate with neodymium β-diketonate and phenanthroline in a supercritical CO2 medium was confirmed by the method of differential thermal analysis. The same method confirmed that with the introduction of these components from the solution of the above systems do not form.

Diverse-ligand phosphor complexes of neodymium acetylacetonate with phenanthroline have been synthesized in polymer matrices (oligourethanmethacrylate, fluoroplast, and polycarbonate) in the medium of supercritical carbon dioxide, while the role of one of the ligands in such complexes is performed by the polymer matrix fragments. The luminescence spectra of the obtained triple systems have been described and it has been shown that the position of the luminescence maxima is bathochromically shifted relative to the Nd(Acac)3/polymer double systems obtained in a similar way and the shift magnitude depends on the polymer matrix nature. It has been shown that when these components are introduced into polymers from a solution, such phosphor diverse-ligand neodymium complexes are not formed. The formation of new Nd(Acac)3/1,10-phenanthroline/polymer structures at the impregnation of oligourethane methacrylate by neodymium β-diketonate and phenanthroline in the supercritical CO2, which are not formed by the introduction of these components from solution, has been confirmed by differential thermal analysis.

A two-stage polylactide modification was performed in the supercritical carbon dioxide medium using the urethane formation reaction. The modification resulted in the synthesis of polymerizable methacrylate derivatives of polylactide for application in the spatial 3D structuring by laser stereolithography. The use of the supercritical carbon dioxide medium allowed us to obtain for the first time polymerizable oligomer-polymer systems in the form of dry powders convenient for further application in the preparation of polymer compositions for photocuring. The photocuring of the modified polymers was performed by laser stereolithography and two-photon crosslinking. Using nanoindentation, we found that Young’s modulus of the cured compositions corresponded to the standard characteristics of implants applied in regenerative medicine. As shown by thermogravimetric analysis, the degree of crosslinking and, hence, the local stiffness of scaffolds were determined by the amount of the crosslinking agent and the photocuring regime. No cytotoxicity was observed for the structures.

Phosphor polymers that exhibit luminescence in the blue region of the spectrum are produced by impregnating thermoplastic polymers with neodymium(III) acetylacetonate in a supercritical carbon dioxide medium. The spectral characteristics of the prepared systems are studied, and an interpretation of the observed change in the nature of luminescence is proposed.

Abstract Polymerizable (meth)acrylate groups were introduced into polylactide (PLA) in the methylene chloride or toluene medium. Polymer modification was carried out both on the carboxyl and hydroxyl groups of polylactide. The efficiency of this modification was studied depending on the type of reaction. It was found that the highest degree of polylactide modification by (meth)acrylate groups (86%) is achieved through the formation of PLA urethane derivatives in the presence of diisocyanates. Samples of photocured, three-dimensionally crosslinked after such a modification polylactides were obtained, their biocompatibility was determined. It was shown that such materials are promising for use in regenerative medicine and tissue engineering.

Hyperbranched 3-dimension (3D) oligophenylenes with a good electroluminescent external quantum efficiency (0.26%) in solution processed organic light-emitting devices were developed by a Ni0-catalyzed cross-coupling reaction of tribromo-substituted triphenylbenzene and triphenylamine.