ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 312

should be taken since steric hindrance introduced by adding additional sequences
to an active peptide or by immobilizing a peptide to a material may result in a
reduction in peptide activity.
4.2. Interaction with ECM components
Reconstruction of ECM for encapsulated cells in 3D scaffolds involves the
organization of ECM components by cells. Organized ECM is recognizable to
cells. In a recent study, when MSCs were seeded onto a scaffold derived from
porcine cartilage tissue, the chondrogenesis could be induced without any
exogenous growth factors [30]. However, physically entrapping ECM
components such as collagen, HA and CS into hydrogels results in the unknown
distorted structures. Therefore, peptides that can bind to ECM components
including collagens, proteoglycans and soluble growth factors provide an
alternative way to retain these molecules to maintain cell favorable niches while
minimally affecting the physical-chemical properties of hydrogels. Collagens are
the major components in ECM of cells and can maintain the growth and
differentiation of both chondrocytes and stem cells. Retaining collagens secreted
by resident cells should improve the efficiency in tissue engineering by
facilitating the organization of ECM produced by resident cells. A collagen
mimetic peptide (CMP, -(Pro-Hyp-Gly) (x) -, where Hyp = hydroxyproline) was
developed and found to be able to binds to type I collagen molecules through a
process involving both strand invasion and triple-helix assembly [207, 208].
When PEG hydrogel is conjugated with CMP, diffusional loss of type I collagen
that was added to the hydrogel was limited [209]. Decorin is a small leucine-rich
proteoglycan (SLRP) and interacts with ECM components such as type II
collagen and growth factors, such as fibronectin and TGF- Ȳ [210]. Therefore,
decorin plays very important roles in matrix organization of cartilage [211, 212].
Specifically, type II collagen is stabilized by binding to decorin at two major
sites, RELH and KLER [213, 214] against collagenase degradation [215].
Therefore, peptides derived from decorin hold potential application in cartilage
tissue engineering by facilitating retaining type II collagen. Heparin binds a wide
variety of growth factors, which are selected to provide suitable inductive cues,
including acidic and basic fibroblast growth factor (aFGF, bFGF) and TGF- Ȳ .
Park et al. [216] entrapped low molecular weight heparin (4500Da)-bound TGF-
Ȳ 3 in p(NiPAAm-co-AAc) hydrogels for chondrogensis of MSCs. On the other
hand, the heparin-binding domains have been derived from anti-thrombin III
(K(bA)FAKLAARLYRKA), modified anti-thrombin III (R(bA)FARLAARLYRRA),