Microenvironment Design for Stem Cell Fate Determination - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 237

3.2 Bio-Inspired Materials and Scaffolds
Moving from the classical application of biomaterials as cell delivery vehicles, to
attempts at replicating the microenvironmental cell niche in order to regulate stem
cell fate, has required the re-design of biomaterials and scaffolds. The re-design
was bio-inspired by the roles of the ECM, including adherence, migration, mec-
hano-signals, growth factor presentation and cell differentiation [ 116 ]. The cues
from the ECM, a complex network of collagen fibers, multi-adhesive matrix
proteins and proteoglycans, have significant impacts on development during
embryonic, fetal and neonatal stages as well as in adult tissues. The ECM network
organizes cells into tissues and regulates cell growth, proliferation and function by
signal transduction processes triggered by binding ECM ligands to cell receptors
[ 117 - 122 ].
Attempts to gain cell recognition have been achieved by surface and bulk
modification of the materials via chemical modification or adsorption of bioactive
molecules, such as native long chains of ECM proteins as well as short peptide
sequences derived from ECM proteins, interacting with cell receptors [ 123 ].
Advanced scaffold designs are now being developed to implement patterning,
binding of ligands, sustained presentation and release of cytokines, and the
structural and mechanical properties of specific tissues [ 124 - 126 ].
3.2.1 Peptide-Modified Scaffolds
Since the finding of signaling domains that are composed of several amino acids
along the long chain of ECM proteins, and their interactions with cell membrane
receptors, the short peptide fragments have been used for surface modification of
materials in numerous studies. Though lacking the complete specificity and
function of native ECM, the synthetic peptides can easily be covalently attached to
the matrix, allowing control over ligand presentation, and thus the elucidation of
cellular behavior on the biomaterial, in a more defined manner.
Moreover, short peptide sequences are relatively more stable during the
modification process than the natural proteins, and nearly all modified peptides
are available for cell binding. In contrast, the native ECM protein tends to be
randomly-folded upon adsorption to the biomaterial surface, and thus the receptor
binding domains are not always available. In addition, short peptides may be
synthesized in large quantities and in relatively less expensive processes than the
native proteins. The modification of materials with individual peptide sequences
and epitopes derived from ECM molecules has proved to be a beneficial approach
to controlling stem cell fate.