The influence of mineral particles on fibroblast behaviour: A comparative study
Graphical abstract
Introduction
Cell fate depends strongly on the physical-chemical properties of the extracellular environment. Cells are able to sense cues from their vicinity and respond with processes such as protein expression, cell differentiation, migration, proliferation, and death [[1], [2], [3]]. Therefore, it is possible to control cell decision-making through the modification of the extracellular features. Current standard methods for cell culture do not facilitate such modifications nor mimic native extracellular environment. Thus, the development of a cell-instructive platform would allow further understanding of the mechanisms underlying cellular processes, and potentially reduce the gap between in vitro and in vivo studies.
Minerals are utilised to modify and improve physical-chemical properties of substrates, including those relevant for the cell machinery, such as surface energy, roughness or porosity. In a race to develop smart environments for cell growth, minerals can provide the means to control and regulate cell behaviour. As particles, minerals can be used as additives in matrices, as fillers, surface coatings or porous packed structures [4]. The versatility of minerals lies in the easiness to manipulate the resulting properties of a system through changes to particle size, shape, hydrophobicity, and surface structure. Size, in particular, is relevant for cell behaviour since nanoparticles can be internalised by cells and potentially exert a toxic response. It is also possible to functionalise mineral surfaces through the adsorption of molecules.
Traditionally, the largest use of minerals, such as calcium carbonates, calcium sulphates, silica, silicates, and titanium dioxide, is in the paper industry, as fillers and in paper coatings [5]. Nowadays, the biological applications of minerals is rapidly expanding. The osteogenic potential of calcium-based minerals is an advantage in bone engineering where they are used as fillers, coatings, implants or scaffolds [[6], [7], [8], [9], [10]]. As part in composites, calcium carbonate provides improved stability for long term use. In contrast, calcium sulphates have a fast resorption rate that, together with its pH-dependent solubility [11], increases locally the concentration of calcium, which is a crucial ion in cell signalling [12]. Additionally, both calcium-based minerals support the encapsulation of biomacromolecules and induce a controlled drug or gene delivery [[13], [14], [15]]. Silica is used in the delivery of biomolecules, cell labelling, cell growth coatings, bone engineering, cancer treatment and in drug tracking studies [[16], [17], [18], [19], [20]]. Natural silica (diatomite) has excellent capabilities for drug delivery and particle functionalisation due to their highly ordered multiporous structures [21,22]. Silicates such as kaolin and zeolite induce the haemostatic response in the body. They are used as clotting agents in commercial wound healing dressings to stop haemorrhagic bleeding [23]. Until recently, biocompatibility studies related to kaolin showed increased toxicity [[24], [25], [26]], yet nowadays kaolin is a promising material for novel drug delivery systems [27,28]. In contrast, literature regarding the influence of talc on cells is limited and/or outdated [[29], [30], [31], [32], [33], [34]] regardless of its unique properties such as high thermal stability, low conductivity, high oil absorptivity, high aerophilicity and hydrophobicity [35,36]. Lastly, the photocatalytic properties of titanium dioxide is applied in photodynamic cancer treatments, coating of implants, drug delivery, cell labelling, biosensing, and genetic modification of cells [37].
Despite the research available on minerals in a biological environment, there are no guidelines to predict how specific cell lines will respond to new samples. Hence, the principles behind the influence of mineral properties on cell behaviour remain to be explored. This article assesses and compares the effect of selected minerals and their properties on cell behaviour. The screening of the minerals helps to elucidate possible future applications in cell-instructive platforms such as the paper-based cell growth platform [[38], [39], [40]].
Section snippets
Materials and methods
Table 1 shows the label, commercial name, material supplier, and general description of the minerals selected for this research. The selected minerals were: calcium carbonates of various sizes, calcium sulphates with different hydrated states, silica of both natural and synthetic origin, several silicates, and titanium dioxide. Commercial grades of minerals often contain additives such as dispersing agents to improve their dispersability in aqueous systems [4]. These additives may affect the
Results and discussion
In this section, first the mineral particles are characterised according to their morphology. Then, the effect of the cell culture media on the minerals is assessed, followed by discussion of the role of the mineral properties on the cellular response of fibroblasts.
Conclusion
In this article, human dermal fibroblasts were treated with different samples of calcium carbonates, calcium sulphates, silica, silicates, and titanium dioxide. Minerals were characterised, and their influence on the fibroblasts behaviour was assessed and compared to their properties. Results show that a shared initial cellular response to the minerals is followed by enhanced proliferation, growth inhibition, or cell damage. Therefore, minerals were grouped according to the cellular response as
Acknowledgments
Doctoral Network of Material Sciences from Åbo Akademi University for the financial support. The FunMat Consortia, more specifically the Laboratory of Prof. John Eriksson for providing the facilities for the cellular studies. All the imaging was possible thanks to the Cell Imaging Core at the Turku Centre for Biotechnology in Turku, Finland.
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