Chemistry Reference
In-Depth Information
The Hartgerink group recently extended the application of PA as a biomimetic tem-
plate in mineralization by synthesizing a series of PAs that were capable of catalyzing
the formation of silica from a tetraethoxysilane precursor (Yuwono and Hartgerink
2007). Typically, the sol -gel reaction is catalyzed by ammonium hydroxide. Lys
and His residues were incorporated into the peptide sequence to act as surface anchored
catalysts through the presence of amine and imidazole groups, respectively, in their side
chains. Because of the difference in their pK
a
values, PAs containing Lys self-assemble
at pH 10 whereas His is at pH 7. Just as with HA and CdS, silica was successfully
formed on the surface of the nanofibers at their corresponding self-assembly pH.
Calcination of the nanocomposite material yields hollow silica nanotubes. The thick-
ness of the silica layer can be tuned bymodulating the length of the PAs. In contrast, the
same experiments with Glu residues did not lead to silica tube formation, because of the
lack of catalytic groups on the surface of the fibers.
PA nanofibers are also widely used in biological applications. Self-assembled PA
gels have desirable properties as ECM mimics in tissue engineering, which include
biocompatibility, mechanical strength tunability, and versatility of the peptide
region to incorporate diverse bioactive functionality, which are demonstrated in
the next example. A peptide amphiphile designed to function as an ECM mimic
incorporated relevant features in its peptide region: 1) a matrix metalloproteinase
(MMP)-2 sensitive sequence (GTAGLIGQ) to allow cell-mediated proteolytic degra-
dation, 2) a glutamic acid and C-terminal carboxylic acid for solubility and calcium
binding, and 3) a cell adhesive sequence (RGDS; Jun et al. 2005). Proteolytic degra-
dation of the gel is necessary for cell migration and cell remodeling of the network.
The density of cell adhesive sites on the nanofiber surface can be controlled by
mixing the PA with another PA containing a nonadhesive sequence (RDGS) at
various ratios. The viscoelasticity and gelation behavior at various Ca
2
þ
to PA
ratios were studied by rheometry. Hydrogel networks were obtained when the ratio
of Ca
2
þ
/PA was 0.5 and the storage modulus continued to increase until the
Ca
2
þ
/PA was equal to 2. Further addition of calcium caused the nanofibers to
form large parallel bundles that phase separated and decreased the mechanical
strength of the gel. The PA gels were incubated in type IV collagenase to evaluate
their enzymatic degradation behavior. The gels lost 50% of their weight in 1 week
and were completely degraded in 1 month. Under TEM, the gels' nanostructure
was observed to have changed from long 8-nm diameter fibers before incubation in
an enzyme to egg-shaped aggregates and twisted ribbons. The data suggested that
cleavage of PA at the MMP-2 sensitive site created defects in the fibers that under-
mined the structural integrity of the fibers and led to the formation of irregular aggre-
gates. The biocompatibility, bioactivity, and biodegradability of the PA gel were
evaluated by encapsulation of MMP-2 producing cells, which were rat maxillary
incisor pulp cells. The density of cell binding ligands was modulated by mixing
PAs with RGDS and RDGS sequences at various ratios. The cells were able to inter-
act with the PA as indicated by cell spreading and elongation. Cells were also able to
proliferate and remodel the scaffold.
Neural progenitor cells were successfully encapsulated in vitro (Silva et al. 2004)
in a manner similar to the previous case, but in this case the PA contained the
