Hydrogels with engineered mechanical properties and degradation rates

Hydrogels are important to the advancement of engineered tissue replacements. They offer variable mechanical properties and the ability to incorporate biological factors and signals into a replacement material that can be used for various applications in tissue engineering such as scaffolds, artificial skin and vascular grafts. Endothelial cell adhesion and the promotion of angiogenesis have been identified as two key factors in the future success of synthetic vascular grafts. Both of these functions can be incorporated into a hydrogel through recombinant DNA technology. Using this technology, proteins containing specific peptide sequences encoding for cellular adhesion, angiogenesis promotion and specific cross-link sites can be engineered. These proteins can then be expressed in Escherichia coli, and then be purified and recovered. The proteins are then cross-linked under physiological conditions with end-functionalized poly(ethylene) glycol, resulting in synthetic hydrogels. Matrix metalloproteinases allow a cell to degrade the extracellular matrix. Specific peptide sequences cleaved at different but known rates by interstitial collagenase, a matrix metalloproteinase can also be engineered into the protein. The degradation rate of the finished hydrogel can then be controlled at the biological level. In the research presented here, a protein-co-polyethylene glycol hydrogel with simultaneous controlled mechanical strength, degradation rate and cellular adhesion was engineered. This was accomplished through design of a protein that contains RGDS and SIKVAV cellular adhesion sequences, varying collagenase degradation sequences, and specific cysteine cross-link sites. While efficient crosslinking was not obtained based in part on the high degree of disulfide bonding within the protein portion of the polymer, the results of this study begin to provide a database from which the mechanical and degradation properties of a material can be designed prior to the synthesis of the material. The information enhanced the understanding of the effect of specific protein sequences on a hydrogel.