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Editorial
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| Nanostructured substrates for biomedical applications | ||||||
| Valentina Mussi | ||||||
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Institute of Microelectronics and Microsystems, National Research Council, Rome, Italy
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| Mussi V. Nanostructured substrates for biomedical applications. Edorium Open 2018;1:4–8. |
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The starting point for a discussion on biomedical applications of nanostructured substrates may well be the obvious observation that properties of materials change dramatically down to the nanoscale, so that a change of methodologies is required for their production and assembly, a change of analytical instruments is needed for their characterization, and novel tools can be designed with special way of functioning. In fact, nanostructured materials are able to probe and influence processes at cellular and molecular level, and their application is potentially able to deeply modify the way in which we perform environmental and clinical monitoring, tissue engineering, biomarking, drug delivery. In particular, biomedical applications of nanostructured systems rely on the development of innovative devices and materials able to interact with sub cellular elements with a high degree of specificity, so to maximize the diagnostic/therapeutic effect but with minimal invasiveness. Clearly, such different perspective requires a complex reshuffling and mixing of diverse disciplines and expertise in order to work at the frontier between physics, biology, chemistry and engineering, as already envisioned by Feynman in 1963*. Microparticles and nanoparticles realized with various materials (metals, silica, polymers, carbon nanotubes, proteins, lipids) have been until now the most frequently suggested and studied diagnostic and therapeutic agent, even if, apart from few exceptions [1], a translation to commercial clinical use has not yet occurred. This is mainly due to difficulties in obtaining a sufficient size and shape uniformity (strongly affecting the overall properties), in optimizing pharmacokinetic behaviour, and in overcoming general concerns about toxicity, biodegradation and excretion [2]. However, a different strategy can be pursued because industrial nanofabrication methods permit nowadays to control the surface texture of materials at the nanoscale, enabling to realize nanostructured substrates to investigate, understand and manipulate cell and molecular response. When surface topographical features become comparable with those of cellular surface components (microvilli, filopodia) and extra-cellular matrix elements (ECM), they can influence cell adhesion [3] and proliferation [4], cell morphology [5] and alignment [6], cell differentiation [7] and migration [8], but can also affect actin formation [9] and cause alkaline phosphatase [10] and gene upregulation [11]. Man-made nanotopography has thus enormous potential application in implant design and tissue engineering, allowing to realize scaffolds and biodegradable structures mimicking microscale and nanoscale natural tissue organization and enhancing vascularization and in vivo tissue regeneration [12]. In this context, some interesting attempts have been recently made to push further forward the similarity with naturally occurring structures [13]. In taking inspiration from insect wings, bioinspired randomly oriented anisotropic nanostructures have been produced by reactive ion etching on titanium to impart an additional bactericide property to the scaffold, improving the performance for orthopedic in vivo applications [14]. In tissue engineering applications, a relevant role seems to be played also by a certain degree of nanoscale disorder which appears to be able to stimulate cell differentiation at such a degree that the use of osteogenic media could be avoided, with implications for cell therapies [15][16]. The order-disorder transition has the clear advantage of reducing fabrication costs and enhancing production throughput, thus increasing the overall interest on nanostructuring processes for commercial realization of biomedical devices. For example, the combination of bioactive ingredients to be released, such as antimicrobial, antibacterial and anti-inflammatory agents, with fibrous nanostructured materials is considered for next generation of smart wound dressings and healing [17][18], while 3D anisotropic Silicon nanostructures produced by wet chemical etching have been inserted into microfluidic platforms to efficiently capture circulating tumor cells (CTC) from whole blood samples, with the aid of a proper target-oriented functionalization, the key elements being an increased CTC-substrate contact frequency and duration [19]. Even more appealing appears the possibility to produce capturing nanostructures on soft polymeric substrates by means of template assisted methods [20], or replica molding manufacturing [21]. In this last case, nano-cavities on PDMS surface has been successfully used to enhance the adsorption of miRNA molecules, usually present in low concentration in biological fluids, even in the absence of surface functionalization with specific probes. Considering the ascertained role of miRNA as biomarker for several degenerative, contagious or inflammatory illnesses, a similar topography-based trapping mechanism can have a notable application in the field of diagnostic tools for early and not invasive disease detection. Actually, the same elastic properties of polymeric deformable materials can be exploited to tune the nanometric dimension of the realized structures in order to obtain advanced manipulation and sensing capabilities, up to single molecule level [22][23]. A separate discussion must be devoted to approaches where ‘active properties’ of nanostructured substrates are involved. Laser excitation of nanoscale roughened metal surfaces (typically gold or silver) is able to give rise to strong localized surface plasmon resonances that can cause a considerable enhancement of the electromagnetic field. When a target molecule lies in close proximity to the metal surface, a correspondingly large increase of the scattered Raman signal can be observed. This surface enhancement Raman scattering effect (SERS) makes it possible to analyse low concentration samples without the need for fluorescent labelling. Several biosensing frameworks based on SERS substrates have been proposed, both for chemical analysis of cells in routine diagnostic monitoring and for molecular recognition [24], but obtained through different strategies: direct growth of a nanostructured metal film [25][26], by decorating surface nanostructures with metal nanoparticles [27][28], or by covering a nanopatterned layer with a thin metal film [29]. This last solution appears particularly promising because, being based on a low cost-low temperature CVD fabrication process of disordered nanowires, it is compatible with industrial Si based technology, it can be coupled with others analytical methodologies in multi-transduction devices (i.e. Raman plus electrochemical sensing), and it can be applied on polymeric and glass supports to be exploited in standard and endoscopic read-out devices. In fact, multifunctional platforms could play an important role for less invasive biomedical applications, combining imaging, diagnostic and therapeutic capabilities [30]. For instance, as recently demonstrated [31][32], metal covered or decorated nanostructures (gold on silicon nanowires, Au-SiNWs) can also generate significant amount of heat upon irradiation in the near-infrared (NIR) region, where biological tissues and systems are almost transparent, which can be successfully used for inducing thermal drug release or cell death. In principle, it is therefore possible to design and develop specific endoscopic devices based on fiber optic integrated nanostructured interface for NIR photothermal treatment of cancer cells and simultaneous SERS monitoring of the process evolution [33], or to use layered structures for capture and plasmonic phothermal therapy of circulating tumour cells [34]. After all, it can be foreseen that exactly the integration of morphological, mechanical and multifuctional ‘active’ properties will be the future of nanostructured substrates for biomedical applications, as proposed to realize a sort of electronic skin made of wearable or implantable nanostructured devices and sensors for continuous diagnostic monitoring and therapeutic activity [35][36][37]. An open challenge for all those who want to contribute to future progress in this incredible field of research. *If our small minds, for some convenience, divide this glass of wine, this universe, into parts—physics, biology, geology, astronomy, psychology, and so on—remember that nature does not know it!, The Feynman Lectures on Physics, volume I; lecture 3, “The Relation of Physics to Other Sciences”; section 3–7. Keywords: Biomedicine, Cells, Nanostructures, Substrate, Surface enhancement Raman scattering effect (SERS), Tissues |
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REFERENCES
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Author Contributions
Valentina Mussi – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published |
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Guarantor of Submission
The corresponding author is the guarantor of submission. |
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Source of Support
None |
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Conflict of Interest
Authors declare no conflict of interest. |
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Copyright
© 2018 Valentina Mussi. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information. |
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