Soft Matter Composites Interfacing with Biomolecules, Cells, and Tissues - Bioinspired Approaches for Human-Centric Technologies - page 38

reduction in the level of scaffold complexity. Even if these peptides generally elicit
cell response at a higher dose compared to their natural or recombinant counter-
parts, they provide a viable alternative in terms of cost and handling. QK peptide,
for instance, has been proved to be effective in eliciting angiogenic response and
has been already exploited as an alternative to VEGF in promoting scaffolds
(Finetti et al. 2012 ). Analogously, BMP mimetic peptide already proved a potent
osteogenic active molecule (Zouani et al. 2010 ). These small molecules, as their
natural counterparts, often impart a potentiated biological response if bound to a
solid substrate. It has been proved that materials with grafted peptides enhance
tissue formation; such a result points to provide a better integration of the scaffold
with the neoforming tissue (Wang et al. 2007 ). In natural ECM, GAGs (glyco-
saminoglycans) provide binding domains for GFs (growth factor), and this mecha-
nism of action could be encoded within artificial ECM by introducing a specific
binding domain for the mimicking peptides. Alginate and poly(acrylamide) gel, for
instance, have been sulfated to enhance the binding affinity to some GFs, including
VEGF, PDGF, and HGF, potentiating the angiogenic activity and extending the
flexibility of the scaffold for growth factor presentation and preservation (Merkel
et al. 2002 ; Rouet et al. 2005 ; Chaterji and Gemeinhart 2007 ). Furthermore, the
modulation of binding affinity within the scaffolds structure provides a viable
strategy to control stable gradients of GFs (Fig. 2.2 ) or their mimicking peptides,
which are proved to be essential in controlling and guiding morphogenetic pro-
cesses (Griffith and Swartz 2006 ).
In natural ECM, there is a continuous production of GFs that are sequestered
within molecular recess and eventually used upon cell request. Sources of GFs or
their mimicking peptides, at a specific location within a synthetic scaffold, can be
provided with the use of micro- or nanoparticles loaded with bioactive moieties and
programmed to deliver according to a specific profile (Fig. 2.2 ). Integration of
GF-loaded microparticles engineered to release sequentially various GFs has been
already discussed in the literature (Luciani et al. 2008 ; Richardson et al. 2001 ;
Saltzman and Olbricht 2002 ). According to this approach, it is possible to control
the spatial distribution and the gradients of bioactive agents at different locations
within the scaffold (Luciani et al. 2008 ; Borselli et al. 2007 ; Chen et al. 2007 ). A
more advanced method to manufacture microsphere-integrated scaffolds able to
regulate GFs release kinetics both temporally and spatially may take advantage of
micromanipulation-based techniques. Possible developments and advancement
include the control over the presentation of relevant signals, not only within the
physical domain of the scaffolds but also within the host surrounding tissues.
Microdepot acting as a single point source may be micropositioned by 3-D printing
and soft lithography to obtain highly regulated structures able to trigger the extent
and possibly the architecture/structure of tissue formation (Sun et al. 2004 ;
Whitesides et al. 2001 ). The combination of micropositioning systems and mathe-
matical modeling describing the complex and multiple mechanisms governing the
release kinetics from single microspheres within the scaffold can be of help in
creating scaffolds with a highly controlled architecture using computer-aided
scaffold design programs (CASD) (Whitesides et al. 2001 ; Hutmacher et al. 2004 ).