Applications of fabricated micro- and nanostructures in biomedicine

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Introduction Micro- and nanostructures are widely found in nature, although by virtue of their size, they are individually invisible to the naked eye. The utility of these structures, however, are often manifested in their cumulative effect, which may be optical (butterfly wing),1 adhesive (gecko feet),2 or mechanical (muscle)3 in nature. Another class of natural micro-/nanostructures with profound influence in the development and maintenance of organisms, but which is even less apparent, is structures that affect cell behavior and function. This class of “biological structures” is of great relevance with regard to application in areas of biology and medicine and will thus receive greater emphasis in the present review. By understanding how fabricated structures interact with their biological counterparts of the same length scale, one can gain an understanding of how laser-based fabrication may be effectively applied in biomedicine.

Importance of nanostructured features in biology and medicine In examining the importance of micro- and nanostructures in nature in relation to those that are fabricated, it is instructive to first look at the different length scales of biological objects

(Figure 1). At the lower end of the spectrum (2–10 nm), one finds the basic unit of heredity, DNA, as well as other biological molecules such as proteins, polysaccharides, and glycoproteins. Moving one notch higher on the length scale (10–200 nm), we find the subcellular structures, such as the cell membrane, protein complexes (gap junctions, focal adhesion complexes), and intracellular organelles, the latter of which may span several microns. At a length scale of 1–25 μm, the major biological structure is the cell. Micro-tissue structures, such as tubules, follicles, cysts, and glands, are seen at length scales of several hundred microns, while other tissues and organs are formed at mm length scales and larger. Fabricated structures of a particular length scale correlate with natural structures of the corresponding dimensions and interact accordingly to produce the designed response. As an illustration, consider a culture of cells on a two-dimensional (2D) extracellular matrix (ECM)-micropatterned substrate, where the ECM-free areas are non-cell adhesive (Figure 2). Such micropatterns can be formed using focused lasers at dimensions that allow only a single cell to occupy and adhere to each micropattern (Figure 2a). The microstructure consists of components at two length scales—the ECM molecules

Tseng Ming Hsieh, Institute of Bioengineering and Nanotechnology, Singapore; [email protected] Andrew C.A. Wan, Institute of Bioengineering and Nanotechnology, Singapore; [email protected] Jackie Y. Ying, Institute of Bioengineering and Nanotechnology, Singapore; [email protected] DOI: 10.1557/mrs.2011.268

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MRS BULLETIN • VOLUME 36 • DECEMBER 2011 • www.mrs.org/bulletin

© 2011 Materials Research Society

APPLICATIONS OF FABRICATED MICRO- AND NANOSTRUCTURES IN BIOMEDICINE

Figure 1. The length scales of biological objec