ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 316

synthesized. Two molecules of Acryl-PEG-NHS were attached to one molecule
of the peptide to make macromers. The extent of incorporation of peptides can
easily be controlled with minimal influence on the physical properties of
hydrogels. The degradable peptide sequences with two primary amines in the
sequences such as GGLGPAGGK (collagenase-sensitive) and AAAAAAAAAK
(elastase-sensitive) were reacted with Acryl-PEG-NHS to generate block
copolymer, which are then crosslinked as PEGDA [229, 246].
Combination of different chemistries can be exploited to construct more
exquisite biological cues into hydrogels. Lutolf et al [247] attached a RGD
peptide (RGDSP) to vinylsulfone-functionalized PEGs and cross-linked the
macromers with MMP-sensitive peptide sequences. RGD peptide enhances the
cell adhesion, while MMP-sensitive peptide attributes the cell-responsive
degradation to hydrogels. In addition, using recombinant DNA technology, a
laminin-derived peptide (PPFLMLLKGSTR, which has a strong affinity for ŋ 3 Ȳ 1
integrin) was able to be fused with a collagen-binding polypeptide domain at
either one terminus or both termini [37]. Therefore, multi-functional peptides can
be synthesized for conjugation into hydrogels.
5.3. Direct designing self-assembling peptides
New developments in peptide chemistry (e.g., self-assembling peptides) have
greatly enhanced its application in biomaterials [248]. As mentioned before, by
appropriate designing of peptide sequences or including a hydrophobic chain,
peptides can be afforded capability of self-assembling into macroscopic
hydrogels in cell-favorable conditions. Furthermore, different bioactive motifs
can be constructed into self-assembling structures thereby self-assembling of
peptides presents another way of incorporating peptides into hydrogels. The
hydrogels prepared by self-assembling of peptides without any bioactive motifs
has been shown to support the chondrogenic phenotype of encapsulated
chondrocytes [19]. Introducing bioactive sequences into the self-assembling
peptides will improve the efficiency of cartilage tissue engineering. For example,
a laminin derived peptide, IKVAVPA, could be designed into a peptide
amphiphile to promote neurite sprouting and to direct neurite growth [249]. In
another study, a peptide amphiphile was designed to be consisted of different
domains [250]. The peptide sequence contained an MMP-2-cleavable site
composed of GTAGLIGQ; a glutamic acid to assist in calcium binding for self-
assembling; and a cell-adhesion sequence, RGDS. Even though few reports
could be found in literatures about the application of self-assembling peptides in