(182i) Structure-Function Relationships in Peptoid Cross-Linked Hydrogels

Hydrogels show considerable promise in a number of fields including drug delivery, tissue engineering, and 3-dimensional cell culture due to their ability to simulate the physical properties of biological tissues. Unfortunately, it can be difficult to tune these properties of hydrogels independently. For example, the elastic modulus is frequently controlled by increasing the cross-linking density in the polymer network. This coupling intrinsically links hydrogel stiffness to permeability and ligand density within a hydrogel system, which can affect cell migration, proliferation, and differentiation. Thus, there is significant interest in development of a hydrogel system with tunable mechanical properties decoupled from cross-link density. Toward this end, we have developed hybrid materials consisting of classic, synthetic polymer building blocks (i.e. polyethylene glycol) cross-linked with sequence specific oligomers of N-substituted glycines (peptoids) through thiol-ene photo-click chemistry. Peptoids are of particular interest due to their large chemical diversity, tunable persistence length, and high degree of structural control. Particularly, their lack of backbone-backbone hydrogen bonding allows for induced secondary structure with a wide range of bulky, chiral monomers. This allows for impressive structural control of the cross-linkers. Specifically, we have been investigating two peptoids: the chiral, helix inducing sequence (NsceNsceNspe)₆ and an achiral stereoisomer with the same chain length. Here Nspe refers to (S)-N-(1-phenylethyl)glycine while Nsce is (S)-N-(1-carboxyethyl)glycine. We hypothesized that these molecules, which will differ only in secondary structure and thus chain rigidity, will impart different stiffness to the hydrogel system. These peptoids were successfully synthesized via solid phase submonomer synthesis with additional cysteamine-based residues to use in cross-linking on both termini. After purification by high performance liquid chromatography (HPLC), the secondary structures of both peptoids were investigated by circular dichroism (CD). It was determined that the secondary structure of the chiral peptoid showed significant helical character, as had been previously reported. The achiral, however, showed no peaks and was therefore determined to lack the helical secondary structure found in the chiral peptoid. Next, 4-arm polyethylene glycol (PEG) was functionalized with norbornene groups that would be used in cross-linking. Hydrogels were formed via thiol-norbornene photo-click chemistry by irradiating with UV light. Initial rheological data indicates a marked difference between the chiral and achiral cross-linked hydrogels. This new method for altering stiffness while maintaining a constant cross-linking density is a promising step forward in hydrogel structure-function control and allows further design and tunability of hydrogels for specific applications of interest.