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Drug treatment of glioblastoma, the most aggressive and widespread form of brain cancer, is complicated due to the difficulty of penetration of chemotherapeutic drugs through the blood-brain barrier (BBB). Moreover, with surgical removal of tumors, in 90 % of cases they reappear near the original focus. To solve this problem, we propose to use hydrogel based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) (CNC-g-PNIPAM) as a promising material for filling postoperative cavities in the brain with the release of antitumor drugs. The CNC-g-PNIPAM is formed by "grafting to" method for precise control of molecular weight and grafting density. This colloidal system is liquid under injection conditions (at r. t.) and turns into a gel at human body temperature (when filling the postoperative area). It was shown for the first time that due to the rod-shaped of CNC, the gel has a fibrillar structure and, thus, mechanical properties similar to those of brain tissue, including nonlinear mechanics (strain-stiffening and compression softening). The biocompatibility of the hydrogel with primary brain cells is demonstrated. In addition, the release of the antitumor drug paclitaxel from the hydrogel and its antitumor activity is shown. The resulting nanocolloid system provides an innovative alternative approach to filling postoperative cavities and can be used for postoperative treatment due to the programmable release of drugs, as well as for in vitro modeling of tumor interaction with the BBB affecting drug transport in the brain., Competing Interests: Declaration of competing interest Sofia Morozova reports financial support was provided by Russian Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A fibrillar hydrogel was obtained by covalent crosslinking via Diels-Alder reaction of two types of cellulose nanocrystals (CNCs) with furan and maleimide groups. Gelation has been studied at various ratios of components and temperatures in the range from 20 to 60 °C. It was shown that the rheological properties of the hydrogel can be optimized by varying the concentration and ratio of components. Due to the rigid structure of the CNCs, the hydrogel could be formed at a concentration of at least 5 wt%; however, it almost does not swell either in water with pH 5 or 7 or in the HBSS buffer. The introduction of aldehyde groups into the CNCs allows for the conjugation of physiologically active molecules containing primary amino groups due to the formation of imine bonds. Here, we used benzocaine as a model drug for conjugation with CNC hydrogel. The resulting drug-conjugated hydrogel demonstrated the stability of formulation at pH 7 and a pH-sensitive release of benzocaine due to the accelerated hydrolytic cleavage of the imine bond at pH < 7. The developed drug-conjugated hydrogel is promising as wound dressings for local anesthesia.

Tuberculosis remains one of the major health problems worldwide. Besides the lungs, tuberculosis affects other organs, including bones and joints. In the case of bone tuberculosis, current treatment protocols include necrectomy in combination with conventional anti-tuberculosis therapy, followed by reconstruction of the resulting bone defects. In this study, we compared autografting and implantation with a biodegradable composite scaffold for bone-defect regeneration in a tuberculosis rabbit model. Porous three-dimensional composite materials were prepared by 3D printing and consisted of poly(ε-caprolactone) filled with nanocrystalline cellulose modified with poly(glutamic acid). In addition, rabbit mesenchymal stem cells were adhered to the surface of the composite scaffolds. The developed tuberculosis model was verified by immunological subcutaneous test, real-time polymerase chain reaction, biochemical markers and histomorphological study. Infected animals were randomly divided into three groups, representing the infection control and two experimental groups subjected to necrectomy, anti-tuberculosis treatment, and plastic surgery using autografts or 3D-composite scaffolds. The lifetime observation of the experimental animals and analysis of various biochemical markers at different time periods allowed the comparison of the state of the animals between the groups. Micro-computed tomography and histomorphological analysis enabled the evaluation of osteogenesis, inflammation and cellular changes between the groups, respectively.

Hypothesis: Hydrogels based on cellulose nanocrystals (CNC) have attracted great interest because of their sustainability, biocompatibility, mechanical strength and fibrillar structure. Gelation of colloidal particles can be induced by the introduction of polymers. Existing examples include gels based on CNC and derivatives of cellulose or poly(vinyl alcohol), however, gel structure and their application for extrusion printing were not shown. Hence, we rationalize formation of colloidal gels based on mixture of poly(N-isopropylacrylamide) (PNIPAM) and CNC and control their structure and mechanical properties by variation of components ratio., Experiments: State diagram for colloidal system based on mixture of PNIPAM and CNC were established at 25 and 37 °C. Biocompatibility, fiber diameter and rheological properties of the gels were studied for different PNIPAM/CNC ratio., Findings: We show that depending on the ratio between PNIPAM and CNC, colloidal system could be in sol or gel state at 25 °C and at gel state or phase separated at 37 °C. Physically crosslinked hydrogels were thermosensitive and could reversibly change it transparency from translucent to opaque in biologically relevant temperature range. These colloidal hydrogels were biocompatible, had fibrillar structure and demonstrate shear-thinning behavior, which makes them a promising material for bioapplications related to extrusion printing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Synthetic poly(amino acids) are a unique class of macromolecules imitating natural polypeptides and are widely considered as carriers for drug and gene delivery. In this work, we synthesized, characterized and studied the properties of amphiphilic copolymers obtained by the post-polymerization modification of poly(α,L-glutamic acid) with various hydrophobic and basic L-amino acids and D-glucosamine. The resulting glycopolypeptides were capable of forming nanoparticles that exhibited reduced macrophage uptake and were non-toxic to human lung epithelial cells (BEAS-2B). Moreover, the developed nanoparticles were suitable for loading hydrophobic cargo. In particular, paclitaxel nanoformulations had a size of 170-330 nm and demonstrated a high cytostatic efficacy against human lung adenocarcinoma (A549). In general, the obtained nanoparticles were comparable in terms of their characteristics and properties to those based on amphiphilic (glyco)polypeptides obtained by copolymerization methods.

Macroporous monolithic columns with different mean pore size (from 360 to 2020 nm) and appropriate flow-through properties were synthesized using free radical in situ copolymerization of glycidyl methacrylate, 2-hydroxyethyl methacrylate and ethylene dimethacrylate. In order to predict the composition of porogen mixture to generate the pores in the interested size interval, the Hildebrand theory was used. Ribonuclease A and its specific low- and macromolecular substrates cytidine-2',3'-cyclic monophosphate sodium salt and RNA were applied as model system. The effect of mean pore size of macroporous monoliths used for enzyme immobilization on molecular recognition and biocatalytic characteristics was examined. The monitoring of RNA degradation was performed using anion-exchange HPLC on monolithic CIM DEAE analytical column. The high efficiency of heterogeneous biocatalysts obtained comparatively to the catalytic reaction of RNA degradation in solution was demonstrated. Additionally, the series of six monolithic immobilized enzyme reactors with different amount of biocatalyst was prepared and studied regarding to the biocatalytic properties at recirculation mode at two experimental variants, e.g. (i) fixed range of concentrations of circulated substrate solutions, and (ii) fixed range of substrate/enzyme molar ratios., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of sorbents for selective binding of cholesterol, which is a risk factor for cardiovascular disease, has a great importance for analytical science and medicine. In this work, two series of macroporous cholesterol-imprinted monolithic sorbents differing in the composition of functional monomers (methacrylic acid, butyl methacrylate, 2-hydroxyethyl methacrylate and ethylene dimethacrylate), amount of a template (4, 6 and 8 mol%) used for molecular imprinting, as well as mean pore size were synthesized by in situ free-radical process in stainless steel housing of 50 mm × 4.6 mm i.d. All prepared materials were characterized regarding to their hydrodynamic permeability and porous properties, as well as examined by BET and SEM methods. Imprinting factors, apparent dynamic dissociation constants, the maximum binding capacity, the number of theoretical plates and the height equivalent to a theoretical palate of MIP monoliths at different mobile phase flow rates were determined. The separation of a mixture of structural analogues, namely, cholesterol and prednisolone, was demonstrated. Additionally, the possibility of using the developed monoliths for cholesterol solid-phase extraction from simulated biological solution was shown., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)