engleski

Transition metal ions as a tool for modulating the properties of chitosan hydrogels

The synthesis of biologically active scaffolds is focused on the design of a cell-sensitive surface by applying cell adhesive proteins or bioceramic micro (nano) particles. The new strategy for controlling the biological properties is based on the modification by trace metals found in the living organism. Recently, the new approach focusing on the metallic ions that induce certain biological responses in the bone remodelling has emerged. Divalent metal ions such as Sr2+, Mg2+, Cu2+, Zn2+ etc. are essential for cell life during bone formation [1]. The aim of this work was to modulate the physical and biological properties of chitosan hydrogels by the addition of divalent metal ions at non-toxic concentration level. Chitosan is a biocompatible and biodegradable polymer which can be used as a scaffold in tissue engineering [2, 3]. Depending on the degree of deacetylation and molecular weight of polymer, hydrogels with specific structures can be produced by the addition of copper and zinc ions (Cu2+ and Zn2+). Zinc plays a critical role in synthesis of nucleic acids, inhibits osteoclast differentiation and exhibit anti-inflammatory and antibacterial effect [4]. On the other hand, copper is vital for normal functioning of human life through the interaction with enzymes [5]. Cu is known to be angiogenic agent increasing the expression of proangiogenic and growth factors such as VEGF or FGF-2 and stimulates the proliferation of endothelial cells [6]. As a potential method, the complexation can be used to prepare hydrogels of complex chitosan-metal ion with defined structure. Prepared hydrogels were transformed into xerogels by the lyophilisation method and characterised by Fourier transform infrared spectroscopic analysis (FTIR) and qualitative X-ray diffraction analysis (XRD). The morphology and microstructure of the samples was imaged by scanning electron microscopy (SEM), while swelling capacity was determined at physiological conditions (pH = 7.4 at 37 °C). The cytotoxicity of metal ion-chitosan xerogels was evaluated by MTT test performed on human embryonic kidney cells (Hek293) during three days of culture. Due to the strong affinity of metal ions towards amino groups of chitosan, defined and ordered structures of metal ion-chitosan hydrogels were obtained. The physical and biological properties of complex hydrogels varied in metal ion concentration-dependent manner. According to the cell culture with human embryonic kidney cells (Hek293), copper-chitosan systems exhibited higher cytotoxicity when increasing c(Cu2+) and more stable structure. On the contrary, zinc-chitosan complex hydrogels did show lower stability, but significantly higher biocompatibility with respect to the copper-containing hydrogels. Transition metal ions, Cu2+ and Zn2+, show good potential to be used in tailoring the hydrogels microstructure and biological response to the material. Depending on the metal ion type and concentration, structure of chitosan hydrogel is changed from randomly porous to well order tubular. Toxicity of copper-chitosan xergoels is limited by narrow range of concentration, while zinc-chitosan xerogels indicate positive influence of cell growth. However, the lack of extensive studies indicates the necessity for more detailed investigations on biological properties of transition metal ions.

chitosan ; metal ion ; complexation ; microstructure ; cytotoxicity

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