Abstract
The adhesion, proliferation, and migration of cells over nanomaterials is regulated by a cascade of biochemical signals that originate at the interface of a cell with a substrate and propagate through the cytoplasm to the nucleus. The topography of the substrate plays a major role in this process. Cell adhesion molecules (CAMs) have a characteristic size of some nanometers and a range of action of some tens of nanometers. Controlling details of a surface at the nanoscale—the same dimensional over which CAMs operate—offers ways to govern the behavior of cells and create organoids or tissues with heretofore unattainable precision. Here, using electrochemical procedures, we generated mesoporous silicon surfaces with different values of pore size (PS ≈ 11 nm and PS ≈ 21 nm), roughness (Ra ≈ 7 nm and Ra ≈ 13 nm), and fractal dimension (Df ≈ 2.48 and Df ≈ 2.15). Using electroless deposition, we deposited over these substrates thin layers of gold nanoparticles. Resulting devices feature (i) nanoscale details for the stimulation and control of cell assembly, (ii) arrays of pores for drug loading/release, (iii) layers of nanostructured gold for the enhancement of the electromagnetic signal in Raman spectroscopy (SERS). We then used these devices as cell culturing substrates. Upon loading with the anti-tumor drug PtCl (O,O′-acac)(DMSO) we examined the rate of adhesion and growth of breast cancer MCF-7 cells under the coincidental effects of surface geometry and drug release. Using confocal imaging and SERS spectroscopy we determined the relative importance of nano-topography and delivery of therapeutics on cell growth—and how an unbalance between these competing agents can accelerate the development of tumor cells.
Highlights
Tissue engineering is a combination of techniques and materials for the fabrication of scaffolds and devices that, interacting with the cells, can lead to the formation of an analogue of tissues and organs that can improve, assist, or replace those already existing in the human body [1,2,3,4]
Tuning the parameters of the electrochemical etching, we obtained two different pore morphologies: (i) mesoporous silicon samples with a pore size that oscillates around the central value PS = 11 nm (MeP1 silicon with a pore size in the lower nanometer range) and (ii) mesoporous silicon samples with an average pore size PS = 21 nm (MeP2 silicon with a pore size in the higher nanometer range)
The porosity or void fraction is a measure of the void spaces in a material, it is a fraction of the volume of voids over the total volume, expressed here as a percentage between 0% and 100%: it was calculated following the image analysis algorithms reported in the Supporting Information 1 of Supplementary Materials
Summary
Tissue engineering is a combination of techniques and materials for the fabrication of scaffolds and devices that, interacting with the cells, can lead to the formation of an analogue of tissues and organs that can improve, assist, or replace those already existing in the human body [1,2,3,4]. The biomaterials to be used in tissue engineering should exhibit the most convenient combination of mechanical properties, macro-scale architecture, and nanoscale geometry, to influence the collective behavior of cells and induce cells to form efficient structures. Those structures should be biocompatible, energetically efficient, autonomous, computationally efficient, and should be organized in a way to optimize the exchange of biochemical signals, nutrients, and oxygen between the several different parts of the structures and the external environment [1,2,4,5]. This in turn enables to reproduce with an increased level of fidelity the natural microenvironment of cells [28]
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