ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 313

neural cell adhesion molecule (KHKGRDVILKKDVR), or platelet factor-4
(YKKIIKKL) [217, 218]. Therefore, introducing heparin binding sequences
into hydrogels will result in enrichment of heparin, which is then available to
bind a wide variety of heparin-binding growth factors and enables sequestered
growth factors to be slowly released by a cell-mediated degradation of the
scaffolds by heparinase and plasmin enzyme activities. A heparin-binding
domain has been functionalized with a transglutaminase substrate sequence for
subsequent crosslinking to fibrin [217].
4.3. ECM remodeling
Remodeling of ECM is required for cell migration and organization [219].
Therefore, designing peptides that can be specifically degraded by proteinases
such as studies collagenase, plasmin, or MMPs secreted by resident cells
will definitely offer attractive properties to hydrogels for tissue engineering.
Many proteinases including MMPs are suggested to be very critical in the
differentiation of chondrocytes and cartilage tissue repair. Studies show
that the upregulation of MMP-13, also known as collagenase-3, occurs
within 7-12 days of hMSC chondrogenesis [220]. Further, the upregulation of
this enzyme coincides with the cell's down-regulation of fibronectin as
seen in vivo [221]. MMP-13 is a highly active enzyme often seen in patients
suffering from osteoarthritis, which is known to degrade collagen, decorin,
biglycan, aggrecan and various components of the cartilage ECM
[222-224]. A major MMP-13 cleavage site found on aggrecan, a cartilage
ECM component, is PENFF (proline-glutamic acid-asparagine-phenylalanine-
phenylalanine) [225, 226]. Acrylated hyaluronic acids with low molecular
weights (MW 50,000 Da and 10,000 Da) were crosslinked with MMP-sensitive
peptides (GCRDGPQGIWGQDRCG) [227]. The hydrogels prepared could be
degraded by both hyaluronidase and collagenase.
5. Strategies for Bioconjugation of Peptides with Hydrogels
5.1. Pendant attachment of peptides
Attachment of peptides to polymers via covalent linkage formation is the straight
forward way to present biological cues into hydrogels. Natural and synthetic
polymers normally bear diverse functionalities, e.g., hydroxyl, carboxylate and
amine, which are available for chemical conjugations while peptides normally