Tuning material properties via peptide design and photopolymerization of self-assembled peptide based hydrogels

Date
2009
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Self-assembly of de novo designed peptides is a promising approach towards fabrication of functional materials. Hydrogels are one such class of materials, which are highly hydrated and mechanically rigid, and show potential as scaffolds for tissue engineering and drug delivery applications. Schneider and Pochan labs have developed a strategy to fabricate three-dimensional scaffolds for biomedical applications employing self-assembling beta-hairpin peptides. These 20 amino acid peptides can be triggered to fold and self-assemble in response to environmental cues such as pH and ionic strength, which then leads to formation of a physically crosslinked mechanically rigid hydrogel. A hallmark of these hydrogels is that they can be syringe delivered to a target site with spatial and temporal resolution. This property has been investigated towards development of injectable hydrogels for therapeutic and cellular delivery. ☐ An important criterion for development of scaffolds for tissue engineering applications is that the mechanical properties of the engineered scaffold should be similar to the mechanical properties of the native tissue to restore normal function. A limitation of many physically crosslinked hydrogels is that they are mechanically weak. A potential approach to enhancing the mechanical properties of these hydrogels includes formation of covalent crosslinks through chemical modification of the peptide sequence. This thesis specifically focuses on molecular level design of stimuli responsive self-assembling peptides to fabricate hydrogels with enhanced mechanical properties. In particular, two avenues were investigated to construct mechanically rigid hydrogels. First, the beta-hairpin peptides were covalently modified with photopolymerizable groups at specific positions to allow covalent crosslinking of the hydrogel network. In addition, peptide-polymer hydrogel constructs were prepared using self-assembling peptides and bifunctional polymers to create interpenetrating network hydrogels with enhanced mechanical properties. The material rigidity of the interpenetrating networks could be modulated depending upon the method of its preparation. Second, self-assembling, three-stranded antiparallel beta-sheets were designed. These peptides exhibited faster kinetics of self-assembly and formed mechanically more rigid hydrogels than their beta-hairpin counterpart. The mechanical properties of the gels formed by the three-stranded peptides were further modulated by varying the hydrophobicity of the turn region residues. ☐ The results described in this thesis demonstrate that peptide-based hydrogel scaffolds with tailored mechanical properties can be constructed through molecular level design. These hydrogel materials show potential for use as load bearing substitutes for tissue engineering applications.
Description
Keywords
Hybrid hydrogels Hydrogels Injectable delivery Interpenetrating networks Peptide design Peptide materials, Hydrogels, Injectable delivery, Interpenetrating networks, Peptide design, Peptide materials
Citation