Transcript The use of materials patterned on a nano- and micro

The use of materials patterned on a nano- and micro-metric
scale in cellular engineering
C.D.W. Wilkinson, M. Riehle, M. Wood, J. Gallagher, A.S.G. Curtis
Department of Electrical Engineering and Centre for Cell Engineering, Glasgow G12 8QQ, Scotland, UK
Materials Science and Engineering C 19 2002.263–269
Objective
• Cells are organized in different patterns according to the function they serve
• This organization is dictated by chemical and physical signals such as
topographical cues from the environment
• Understanding cell response to topography is crucial for successful design of
bioengineered implants (e.g. artificial heart)
• This paper deals with cell response to topography at the micro- and nano-scale
Fabrication of patterned substrates
additive or subtractive (etching)
Nature Reviews Microbiology 5, 209-218
Master template can be used as mold to create several copies of patterned
substrate, thus reducing cost
Nature Reviews Microbiology 5, 209-218
Molding, embossing and soft lithography are some techniques used for pattern transfer
Studying cell response to topography:
Basic set-up
• Cells are grown on the patterned substrate placed in a petri dish in the
presence of aqueous growth medium consisting of glucose, potassium and
sodium salts and other factors
• Culture dish is maintained in a controlled, sterile atmosphere at 37 C
• Phase contrast microscopy and time lapse photography typically used to
study cell behavior
1. Simplest topographic feature: grooves
• Most cell types align length-wise
to the groove
• Cell response dictated by groove
dimensions and spacing
Fig. 1. Grooves 7 um wide, 3 um deep and spaced by 14 um.
2. Cell response to adhesive patterning
6h
24 h
• Specific cues (adhesion
molecules such as certain
proteins) can be patterned
on the substrate
• Alternative to topographic
patterning
36 h
48 h
• Example: can be used to
selectively trap bacteria for
pathogen detection
3. Response to nano-patterning
Regular vs. irregular spaced features
Fig. 7. Rat tendon cells in the upper half of micrograph while no cell in the
lower nano-patterned area. Substratum was a silica wafer, patterned with
100-nm pillars on 300-nm centre to centre spacing.
Micrograph taken after 21 days in culture.
• Lack of cell growth on nano-patterned region
• Useful for applications like stent engineering
Fig. 8. Array of pillars in silicon. a. Gold beads,
50 nm in diameter deposited onto a silicon
wafer. b. Relief patterns of pillars made by dry
etching gold beads
Conclusion
• Surface microstructure mediates cellular organization and cell migration
• Fabrication techniques such as soft lithography in particular offer
immense scope for further exploring cell-surface interactions and
manipulating single cells
• Huge potential for several bioengineering applications such as implant
design, drug delivery, biosensors etc.