BIOMIMETIC MATERIALS FOR ENGINEERING OF NEURAL TISSUES: CONTROL OF CELL ADHESION AND GUIDING NEURAL CELL OUTGROWTH WITH PEPTIDE-CONJUGATED POLYMER STRUCTURES - Biologically-Responsive Hybrid Biomaterials - page 344

in vivo. These similarities may enhance scaffold integration. Secondly, the high
water content of hydrogels facilitate ion and nutrient exchange and the elasticity
is reminiscent of soft tissues [34]. Pure peptide scaffolds are biodegradable
and the byproducts of chemical breakdown are free amino acids, which can be
metabolized by adjacent cells or excreted in urine. Finally, synthetic peptides are
free of biological contaminants and have reduced immunogenic responses [35].
Multiple in vitro studies involving hybrid peptide-hydrogels have shown
potential for CNS applications. For example, photopolymerizable PEG
(polyethylene glycol) hydrogels conjugated with RGDS, IKVAV and YIGSR
ligands were used to evaluate cell adhesion and neurite extension with a PC-12
cell system. Neurite extension of PC12 cells was greatest on RGDS-PEG
hydrogels compared to PEG-IKVAV. Cells adhered to but did not extend
neurites on hydrogels with YIGSR [36]. The degree of cell adhesion changed as
a parameter of peptide concentration and longer neurites were observed on more
compliant hydrogels. Acrylamide based gels patterned with IKVAV also showed
excellent adhesion properties, where cultured neurons remained on function-
alized surfaces for over 4 weeks and formed viable synapses [37].
In other cases, pure peptide scaffolds have been designed from a
“bottoms up” supramolecular chemistry approach. Silva et al. [38], synthesized

A B

Fig. 4. (A) A schematic outline of laminin protein. Several important binding sites within laminin
have been identified for application in peptide engineering. (B) Top: Molecular model of a self-
assembling peptide sequence named RADA-16. Bottom: Scanning electron micrograph of the
nanofibrillar hydrogel formed by RADA-16 aggregates. Reprinted with permission from [99].