NANOTECHNOLOGY: A TOOLKIT FOR CELL BEHAVIOR - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 8

1.2.2.2 Self-Assembling Nanofibers
Besides the aforementioned self-assembling nanotubes, natural peptides have demonstrated the abil-
ity to self assemble into a highly ordered, nanofibrous scaffolds in aqueous solution. These peptides
possess an ionic self-complementary structure derived from positive and negative side chains on one
side of the b -sheet. In addition to this self-complementary system, the amphiphilic character, that is
to say containing many hydrophobic and hydrophilic features, of the peptides enables hydrophilic
interactions with water molecules. These unique features contribute to the formation of a hygroscopic
nanofibrous hydrogel network, with the hydrophobic regions associated into a double sheet, resulting
in the formation of the nanofibers ( Hauser and Zhang, 2010 ). For instance, Hartgerink et al . reported
that a self-assembly peptide-amphiphile with the cell-adhesive RGD (Arg-Gly-Asp) self-assembled
into supramolecular nanofibers and aligned nHA on their long axis for bone application ( Hartgerink
et al . , 2001 ). Hosseinkhani et al . showed significantly enhanced osteogenic differentiation of stem cells
in a 3D peptide-amphiphile scaffold compared to 2D static tissue culture ( Hosseinkhani et al . , 2006 ). In
addition, Shah et al . designed peptide-amphiphile nanofibers that display a high density of transform-
ing growth factor b 1 (TGF- b 1) binding sites for improved cartilage regeneration ( Shah et al . , 2010 ,
Aida et al . , 2012 ).
Simpler peptides can be leveraged as self-assembly nanomaterials for neural applications as well,
such as isolucine-lysine-valine-alanine-valine (IKVAV) ( Silva et al . , 2004 ), and RADA-16 ( Gelain
et al . , 2006 ). Because the peptides used in self-assembled scaffolds are derived from biology, the re-
sulting nanofibrous scaffolds are similar to natural ECM and present excellent biomimetic properties.
Peptide nanofibers have become the most widely investigated self-assembling nanobiomaterials for
tissue engineering.
1.2.3 POLYMERIC AND CERAMIC NANOBIOMATERIALS
1.2.3.1 Polymeric Nanobiomaterials
As the largest biomaterial group, polymers play an important role in complex tissue engineering.
Polymeric nanobiomaterials are extremely customizable through a variety of processing methods and
chemical modifications, and are common in the clinical environment. This leaves researchers with
many practical, clinically ready and FDA-approved options. One very common application of poly-
mers as nanomaterials is in the creation of therapeutic drug-loaded nanoparticles for sustained and
targeted delivery to cells and tissue ( Parveen et al . , 2012 ). Considering that the process of proving a
new biomaterial to the FDA as safe and effective is expensive and time-consuming, many research-
ers have begun extending the application of current biocompatible polymers already approved by the
FDA for other medical devices for use in drug-loaded nanoparticle fabrication. For instance, polylactic
acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and various hydrogels
currently are generating huge interest from scientists for their potential for numerous regeneration ap-
plications due to their excellent biocompatibility, suitable mechanical properties, biodegradability, and
ease of modification for different applications. A myriad of well-designed polymer-based nanoparticles
loaded with growth factors or other therapeutics have been created for tissue engineering applications
( Dhandayuthapani et al . , 2011 ; Castro et al . , 2012a ).
As we know, various transforming growth factors (e.g., TGF- b 1 and TGF- b 3), and bone morpho-
genic proteins (e.g. BMP-7, BMP-6, or BMP-2) have been shown to improve bone and cartilage re-
generation ( Noel et al . , 2004 ; Sekiya et al., 2001 ; Bai et al . , 2011 ; Chim et al . , 2012 ; Kim et al . , 2012 ).