ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 307

Recombinant proteins due to possible artificial manipulation with rational
design present another attractive source of biomaterials. These large molecular
weight polymers normally consist of repeating blocks of peptides with precise
composition, sequence and length and generally are biocompatible [129].
Elastin-like polypeptides (ELPs) consisting of oligomeric repeats of the
pentapeptide sequence Val-Pro-Gly-Xaa-Gly (Xaa is any amino acid except
proline) are one example, which can form hydrogels above the inverse phase
transition temperature ( T t ) and have been applied for cartilage tissue engineering
[130]. The chondrogenic phenotype of chondrocytes could be maintained when
encapsulated in ELP-hydrogels [131]. The chondrogenic differentiation of MSCs
could be induced in these hydrogels even without the additional chondrogenic
supplements such as TGF- Ȳ 1 and dexamethasone [132]. Further modifications to
make them more bio-recognizable will be possible via genetic design to obtain
optimal scaffolds [133]. Another similar polypeptide is the silk-elastin-like
protein copolymer SELP-47 K, composed of four silk-like blocks, seven elastin-
like blocks, and one modified elastin block containing a lysine (K) substitution
[134]. SELP-47 K can also gel at physiological temperature and has been proved
to support the chondrogenic differentiation of hMSCs [134]. By recombinant
technology, polypeptides consisted of repeating sequences of a specific domain
of type II collagen responsible for chondrocyte migration were also constructed
and shown to support chondrogenesis [118].
2.4. Self-assembling peptide-based hydrogels
Hydrogels prepared by self-assembling of peptides present another promising
class of scaffolds for cartilage tissue engineering [19, 135, 136]. Synthetic
peptides with designed peptide sequences of alternating ionic hydrophobic and
uncharged hydrophilic side groups (e.g., RAD-, ELK-, ELD- and EAK-based
peptides) form stable Ȳ -sheets of interwoven nanofibers at physiological
conditions [137], which resemble the intricate fibrillar architecture of natural
ECM. RAD16-I, a AcN-(RADA) 4 -CONH 2 peptide has been commercially
available for tissue culture [138]. These hydrogels have been shown to
accommodate the differentiation of chondrocytes and MSCs, are highly
biocompatible and can be constructed to bear cell-recognizable peptide
sequences [136]. Another class of self-assembling peptides, so called peptide
amphiphiles are peptides coupled with short fatty acid chains thereby
amphiphile, which are also able to self-assemble into nanofibrous structures and
then form gels by trapping water macroscopically [139-141]. In this case, the