3-D self-assembling leucine zipper hydrogel with tunable properties for tissue engineering

Peptide-based engineered hydrogel scaffolds present several advantages over traditional protein or polymeric hydrogels by imparting more robust control over hydrogel properties. In this manuscript, we report the synthesis and characterization of a leucine zipper (LZ) based self-assembling hydrogel for use in tissue engineering applications. Although, LZ hydrogels posses several advantages, the stability of these hydrogels has always been elusive. In this study, we have standardized the procedure for creating a stable LZ hydrogel. Pore-size was tunable by altering the peptide concentration from 7% to 12% by weight. In order to create a microenvironment for cell adhesion, the LZ polypeptide was functionalized by the incorporation of the cell attachment RGD domain. In vivo implantation of the LZ scaffolds in a mouse model showed absence of foreign body reaction to the scaffold. In vivo experiments with human marrow stem cells (HMSCs) in immunocompromised mice showed the biological property of the hydrogel to promote cell attachment, proliferation and its ability to support neovascularization. Our results show for the first time, that it is possible to generate a functional and stable LZ scaffold that can be used in vivo for tissue engineering applications.