(83a) Photo-Cross-Linkable Physical Hydrogels for Tissue Engineering

Hydrogels have been widely used as 3-dimensional artificial extracellular matrices (ECMs). Most hydrogels used in tissue engineering to date are covalently cross-linked, degradable networks. We have developed photo-cross-linkable physical hydrogels enabling degradation-independent cell migration that mimics non-proteolytic cell migration through physically stabilized ECMs in biological systems. Polymers having a hydrophilic chain flanked by a terminal self-assembling leucine zipper domain and a terminal photoreactive acrylate group have been molecularly engineered to form photo-cross-linkable physical hydrogels. Physical association of the leucine zippers results in multifunctional macromers, which are photo-cross-linkable into hydrogels. Gel formation has been confirmed by rheological measurements. The physical nature of the hydrogel networks has been confirmed by hydrogel disassembly in denaturing solutions that disrupt the secondary structure of the leucine zippers. Outgrowth of encapsulated fibroblast aggregates has been observed in these physical hydrogels, but not observed in a control hydrogel in which leucine zippers are covalently linked. The collective properties of these hydrogels, including the physical nature, the photo-cross-linkable characteristic, and the flexibility for systematic engineering of material properties, will provide unique opportunities for tissue engineering.