Here we show that the efficacy of the chitosan interaction with diglycidyl ethers of glycols significantly depends on pH and the nature of acid used to dissolve chitosan. In solutions of hydrochloric acid, cross-linking with diglycidyl ethers of ethylene glycol (EGDGE) and polyethylene glycol (PEGDGE) at room and subzero temperatures yields mechanically stable chitosan gels and cryogels, while in acetic acid solutions only weak chitosan gels can be formed under the same conditions. A combination of elemental analysis, FT-IR spectroscopy, and solid state 13 C and 15 N NMR spectroscopy was used to elucidate possible differences in the mechanism of chitosan cross-linking in alkaline and acidic media at room and subzero temperatures. We have proved that in acidic media diglycidyl ethers of glycols interacted with chitosan mainly via hydroxyl groups at the C6 position of the glucosamine unit. Besides, not only cross-linkages but also grafts were formed at room temperature. The cryo-concentration effect facilitates cross-linkages formation at −10 °C and, despite lower modification degrees compared to those of gels obtained at room temperature, supermacroporous chitosan cryogels with Young's moduli up to 90 kPa can be fabricated in one step. Investigations of chitosan cryogels biocompatibility in a mouse model have shown that a moderate inflammatory reaction around the implants is accompanied by formation of a normal granulation tissue. No toxic, immunosuppressive, and sensitizing effects on the recipient's tissues have been observed.

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Here, we suggest a theoretical approach to investigations of sorption kinetics based on determination of intrinsic characteristics of heterogeneous sorbents (affinity, quantity, and distribution of the sorption sites in the space of constants of sorption and desorption rates, distribution of the adsorbate on sorption sites at any arbitrary time, and the theoretical sorption isotherm) via calculation of the rate constant distribution (RCD) functions using experimental data obtained by the batch method. The effect of random errors in the experimental data on the stability of the calculated parameters was evaluated using simulation modeling that enables one to reduce time-and labor-consuming experimental procedures without loss in the reliability of sorbent characteristics. The applicability of the suggested approach to real experimental data was demonstrated on the sorption of transition metal ions on supermacroporous polyethylenimine cryogels. We have also shown how experimental conditions in the kinetics batch test affect determination of the sorption and desorption rates and calculation of the theoretical isotherm and how they can be optimized to yield reliable parameters to predict performance of supermacroporous monolith under dynamic conditions.

Macroporous scaffolds (cryogels) for the 3D cell culturing of colorectal cancer micro-tumors have been fabricated by cross-linking chitosan and carboxymethyl chitosan (CMC) with 1,4-butandiol diglycidyl ether (BDDGE) under subzero temperature. Due to the different intrinsic properties and reactivity of CMC and chitosan under the same cross-linking conditions, Young′s moduli and swelling of the permeable for HCT 116 cells cryogels varied in the broad range 3–41 kPa and 3500–6000%, respectively. We have demonstrated that the morphology of micro-tumors can be controlled via selection of the polymer for the scaffold fabrication. Although both types of the cryogels had low cytotoxicity and supported fast cell proliferation, round-shaped tightly packed HCT 116 spheroids with an average size of 104 ± 30 µm were formed in CMC cryogels (Young′s moduli 3–6 kPa), while epithelia-like continuous sheets with thickness up to 150 µm grew in chitosan cryogel (Young′s modulus 41 kPa). There was an explicit similarity between HCT 116 micro-tumor morphology in soft (CMC cryogel) or stiff (chitosan cryogel) and in ultra-low attachment or adhesive culture plates, respectively, but cryogels provided the better control of the micro-tumor’s size distribution and the possibility to perform long-term investigations of drug–response, cell–cell and cell–matrix interactions in vitro.

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