NANOTECHNOLOGY: A TOOLKIT FOR CELL BEHAVIOR - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 7

FIGURE 1.3
(A) Schematic illustration of the self-assembly process of RNTs: six twin DNA motifs are self-assembled into
rosette-like supermacrocycles and then many of them stack up into stable helical nanotubes with a 3-4 nm diameter
and several hundred nanometers long. Atomic force microscopy (AFM) images of (B) RNTs with aminobutane
linker (TBL). (C) SEM image of nHA nucleation on RNTs. Fluorescence microscopy images of increased
endothelial cell growth on (D) 0.001 mg/ml RNTs coated titanium when compared to (E) uncoated sample.
Hematoxylin and eosin staining of (F) controls; and (G) TBL scaffolds for cartilage regeneration at week 1.
with amino acid, peptide, and small molecule side chains. Such side chain groups can be anything, such
as cell adhesive lysine, lysine-arginine-serine-arginine (KRSR), and arginine-glycine-aspartic acid-
serine-lysine (RGDSK) for enhanced and directed osteoblast, chondrocyte, and MSC function, thus
making them intriguing nanomaterials for many types of tissue regeneration ( Zhang et al . , 2008a, 200
8b, 2009c, 2009d, 2010; Fine et al . , 2009; Sun et al . , 2012 ). For instance, it has been demonstrated that
RNTs can significantly enhance osteoblast growth and osteogenic differentiation when compared to
controls ( Sun et al . , 2012 ). It was also observed that RNTs can directly nucleate and align nHA particles
along the long axis of the nanotubes ( Figure 1.3 C) similar to the self-assembled pattern of collagen
and nHA in bone, suggesting that our nanotubes can serve as excellent templates for nHA nucleation
( Zhang et al . , 2009d ). In addition, by thoroughly modulating the RNTs peptide side chains, improved
endothelial cell growth can be obtained on RNTs when compared to controls ( Figures 1.3 D-E) ( Fine
et al . , 2009 ). In our recent work at our lab, we explored MSC adhesion, proliferation, and 4 weeks of
chondrogenic differentiation in twin-based RNTs embedded within poly-L-lactic acid (PLLA) scaf-
folds ( Childs et al . , 2013 ). Our results demonstrated that these biomimetic twin-based nanotubes can
significantly enhance MSC growth and chondrogenic differentiation, collagen, and protein synthesis
( Figures 1.3 F-G) when compared to controls without nanotubes. The biomimetic nanostructure and
high density of peptides with well-organized architecture contributed the greatly enhanced stem cell
functions in vitro .