ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 300

Tissue engineering is a field of exploiting cells and biomaterials to
regenerate or substitute damaged tissues and organs [5]. Articular cartilage is
typically composed of 75-80% water and a solid matrix, that is 50-73% collagen
II and 15-30% proteoglycan macromolecules [6]. While insoluble collagen fibrils
withstand tension, proteoglycans such as aggrecan are resistant to compression,
due to their extremely hydrophilicity. Engineering cartilage tissue ex vivo for
implantation or directly inducing cartilage regeneration in vivo represents an
exciting strategy to recapitulate the biochemical and biomechanical properties of
hyaline cartilage through the appropriate combination of cells (e.g., chondrocytes
and stem cells), scaffolds and biofactors (e.g., transforming growth factor Ȳ ,
TFG- Ȳ and bone morphogenetic proteins, BMPs) [7, 8]. The three-dimensional
(3D) scaffolds not only fill tissue defects and provide the shape, but also is to
mimic the native microenvironment of cells, which is very critical in maintaining
the phenotype of chondrocytes and conducting lineage-specific differentiation of
stem cells [9, 10]. In general, scaffolds should have appropriate porosity for
accommodating cells and permeable to nutrients, waste and gas (O 2 , CO 2 ) and
bearing appropriate biological cues, while with adequate, initial biomechanical
strength, which is especially important for cartilage tissue engineering. Balanced
biodegradable properties that coordinate the rates of neotissue formation are also
desirable, which also facilitate the integration of neo-tissue with host tissue.
Scaffolds in a variety of physical forms (i.e., fibers, sponges, meshes and
hydrogels) have been exploited for cartilage tissue engineering [11]. Hydrogels
due to their high water content, which mimics the native ECM, have been most
attractive by offering many advantages over other scaffold [12-14]. For example,
hydrogels enable homogenous cell seeding. Biofactors and other molecules can
diffuse freely throughout hydrogels. In situ gelation allows hydrogels to
accurately and completely fill irregularly shaped defects [15]. Hydrogel
formation can be initiated via chemical crosslinking (e.g., initiated by redox
reaction or UV radiation), self-assembling (e.g., initiated by temperature and pH
change) and ionic interactions of both natural and synthetic materials. Natural
materials including polysaccharides (e.g., alginate) and proteins (e.g., collagens)
are advantageous because of their inherent properties of biological recognition.
However, the lack of control over the gelation process, the relative weak
mechanical strength and the complexities associated with purification,
immunogenicity and pathogen transmission limit their applications. Synthetic
materials such as poly(ethylene glycol) (PEG) can be easily subjected to
chemical modifications to modulate the composition and structures of hydrogels
[12]. PEG-based hydrogels are particularly exciting, which can be prepared by