ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 301

photopolymerization of PEG-diacrylate (PEGDA) and have been extensively
used in cartilage tissue engineering [16-18]. Recently, nanofibrillar hydrogels
by self-assembly of small peptides, which resembles the structural organization
of native collagen fibrils, may present another attractive material for cartilage
tissue engineering [19].
Optimal hydrogels for cartilage tissue engineering should be
chondroconductive and chondroinductive to facilitate long-term in vivo
phenotypic stability of chondrocytes. To achieve this goal, the interaction
between biomaterials and cells are greatly appreciated [20, 21]. It is recognized
that the most important step is to provide cells (chondrocytes and stem cells)
with an appropriate environment for their growth and differentiation. It is well
known that isolated chondrocytes will lose their differentiated phenotype (so-
called dedifferenation) in two-dimensional (2D) culture [22]. It has been
established that dedifferentiated chondrocytes can recover their differentiated
phenotype when they are relocated into a 3D environment [23-25]. ECM is a
highly hydrated network consisted of fibrillar proteins such as collagens,
noncollagenous glycoproteins such as fibronectin, elastin or laminin and
hydrophilic proteoglycans such as aggrecan and is also a reservoir of soluble
macromolecules such as growth factors, chemokines and cytokines. ECM
sequesters, modulates and potentiates secreted factors such as binding of BMP2
to GAGs [26] and enhancing the bFGF activities by heparin sulfate
proteoglycans [27, 28]. The adhesion, migration, proliferation and differentiation
of cells are regulated by the molecular interactions with these ECM components
[20]. Biophysical and biochemical signals, transmitted from the ECM via various
cell surface receptors and integrated by intracellular signaling pathways,
converge to regulate gene expression and ultimately establish cell phenotype.
Adhesion to fibronectin has been shown to be necessary for pre-cartilage
condensation of chick limb bud cells [29]. In a recent study, MSCs were seeded
onto a scaffold derived by decellularizing porcine cartilage [30]. The
chondrogenesis of MSCs could be induced without any exogenous growth
factors. Therefore, to mimic native extracellular microenvironment for cells is
the most promising strategy for both ex vivo tissue engineering and in vivo tissue
regeneration.
Peptides are the most important signaling transducers and constitute the
recognition domains of proteins and therefore the functionalization of
biomaterials with peptides represents the most important step in preparing
biomimetic scaffolds. It is well known that synthetic polymers are normally bio-
inert to cells. For example, PEG hydrogels lack adhesiveness, which largely