Research Article: Graphene oxide in zinc alginate films: Antibacterial activity, cytotoxicity, zinc release, water sorption/diffusion, wettability and opacity

Date Published: March 7, 2019

Publisher: Public Library of Science

Author(s): Belén Frígols, Miguel Martí, Beatriz Salesa, Carolina Hernández-Oliver, Olav Aarstad, Ann-Sissel Teialeret Ulset, Gerd Inger Sӕtrom, Finn Lillelund Aachmann, Ángel Serrano-Aroca, David Y.W. Ng.


Alginate is considered an exceptional biomaterial due to its hydrophilicity, biocompatibility, biodegradability, nontoxicity and low-cost in comparison with other biopolymers. We have recently demonstrated that the incorporation of 1% graphene oxide (GO) into alginate films crosslinked with Ca2+ cations provides antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, and no cytotoxicity for human keratinocyte HaCaT cells. However, many other reports in literature have shown controversial results about the toxicity of GO demanding further investigation. Furthermore, the synergic effect of GO with other divalent cations with intrinsic antibacterial and cytotoxic activity such as Zn2+ has not been explored yet. Thus, here, two commercially available sodium alginates were characterised and utilized in the synthesis of zinc alginate films with GO following the same chemical route reported for the calcium alginate/GO composites. The results of this study showed that zinc release, water sorption/diffusion and wettability depended significantly on the type of alginate utilized. Furthermore, Zn2+ and GO produced alginate films with increased water diffusion, wettability and opacity. However, neither the combination of GO with Zn2+ nor the use of different types of sodium alginates modified the antibacterial activity and cytotoxicity of the zinc alginates against these Gram-positive pathogens and human cells respectively.

Partial Text

Alginate is considered a very promising material with exceptional hydrophilicity, biocompatibility, biodegradability, nontoxicity and low-cost in comparison with other biopolymers [1]. Its linear structure of (1–4)-linked β-d-mannuronic acid (M) and α-l-guluronic acid (G) residues is arranged in a block wise fashion with M and G present in different proportions and sequences depending on the source of alginate [2,3]. Divalent metallic cations such as Ca2+ and Zn2+ can interact with G-blocks to form, respectively, calcium and zinc alginate hydrogels arranged according to the classical egg-box model [4]. Calcium alginate exhibits negligible antibacterial and cytotoxic activity[5]. However, zinc alginates have shown strong antibacterial activity against a wide range of microorganisms [6–9] due to its inhibition of conserved metabolic pathways involved in synthesis of essential biomolecules or antioxidant depletion[10], and it is well-known that Zn2+ may produce toxic effects in human cells [11]. Alternative materials such as graphene oxide (GO), which from the graphene family shows the easiest processing, larger scale production and less expensive cost [12], has recently exhibited antibacterial capacity and negligible mammalian cytotoxicity in calcium alginate [5]. Thus, some researchers have paid particular attention to the incorporation of GO into polymers as promising candidates for the next generation of antibacterial agents [13–16]. Furthermore, nanocomposites such as polyvinyl-N-carbazole (PVK)-graphene oxide (GO) showed higher antimicrobial activity than pristine GO and no significant cytotoxicity to fibroblast cells [13]. The antimicrobial action of GO is usually associated with membrane disruption, bacteria wrapping, electron transfer mechanism and induction of oxidative stress by reactive oxygen species (ROS)[14,17]. However, the antibacterial activity and cytotoxicity of GO is still an opened question which demands further investigation because there are many controversial results under different conditions in literature. Thus, GO dispersions in isotonic saline solution in direct contact with bacterial cells showed strong antibacterial activity[18]. However, other studies with GO dispersions have shown no antibacterial activity [19] or even faster growth due to bacterial growth stimulation by GO surface for attachment and proliferation[20]. Furthermore, there are many studies that have stated that this carbon nanomaterial is toxic for some human cells[21,22].

Two commercial sodium alginates were characterized and used to synthesize zinc alginate films with and without 1% w/w graphene oxide. These advanced materials exhibited very strong antibacterial activity against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis only due to the presence of Zn2+. Several properties of these hydrophilic materials such as zinc release, water sorption/diffusion, wettability and opacity of these materials showed to be significantly affected by the type of sodium alginate utilised and/or the incorporation of 1% w/w of GO. However, neither the incorporation of GO nor the use of different types of sodium alginates increased the cytotoxicity of the films in human keratinocyte HaCaT cells.




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