Biomedical Engineering Reference
In-Depth Information
activity. PEG-bis-vinylsulfone has been crosslinked by a Michael-type
addition reaction with a peptide containing three cysteine residues (Pratt
et al
., 2004). the presence of these cysteine residues makes the peptide
susceptible to cleavage by cell-associated plasmin, a protease able to digest
ECM protein components. As a consequence, cells contacting this type of
hydrogel were able to invade its network where they interact with grafted
adhesion peptides which were linked to main polymer backbone through
plasmin resistant peptides. When BMP-2 was loaded in these bioresponsive
hydrogels, they were able to induce bone repair
in vivo
in a rat model. this
bone repair potential was improved by the integration of grafted heparin in
the PEG structure, this molecule possessing affinity for the BMP-2. It can be
argued that by introducing BMP-2 binding domains, the ability of the ECM
to bind growth factor was successfully mimicked, creating microenvironments
with relatively high BMP-2 bioavailability. This work confirms the feasibility
of attaining desired biological responses
in vivo
using engineering material
properties through the design of single components at the molecular level. in
these studies, human recombinant BMP-2 was used, providing a very good
example of the technological potential that can be achieved by combining
polymer science with recombinant Dna technology (Rizzi
et al
., 2006).
in a similar approach, RGD- was coupled in a binary (low and high
molecular weight) injectable alginate composition in order to influence
bone cell differentiation in a 3D structure (Evangelista
et al
., 2007). Cells
within RGD-modified alginate microspheres were shown to establish more
interactions with the biomimetic matrix and to express higher levels of
differentiation markers.
importantly, these studies highlight the importance of the grafting strategy
for these types of bioligands; grafting is engineered to provide resistant or
protease-sensitive linkage as well as adequate exposure to the cell receptors.
to achieve this, several chemical strategies have been developed. a review
paper by Hersel
et al
. (2003) offers a very comprehensive overview of the
different grafting methods and highlights the importance of the degree of
exposure of RGD-peptides to cells. indeed, the synthesis of loop-shaped
RGD peptides maximising the exposure of the relevant amino acid sequence
has been shown to support higher levels of cell biorecognition.
It has to be outlined that, although the -RGD- sequence has been the most
investigated, other amino acid sequences are able to support cell adhesion
and migration and, in particular, biospecific interactions with osteoblasts.
Among them the -FHRRIKA- sequence has been shown to favour osteoblast
migration (Rezania and Healy, 1999) and the -KRSR- which promotes
osteoblast adhesion. FHRRiKa and KRSR have in common their ability to
bind proteoglycans (Sawyer
et al
., 2007).
the use of these peptides has to be evaluated in different scenarios as
their active role in cell biorecognition processes may be affected by the
