Mimicking native cryptic sites

This grant focused on making hydrogels that mimic the dynamic nature of native ECM. To this end, we created enzymatically degradable hydrogels with tunable degradation kinetics; we also synthesized switch peptides, which contain non-functional epitopes that rearrange upon activation by an enzymatic trigger, turning the non-functional epitope into a functional one. We developed a synthetic method to use peptide-dendrimers (tree-like polymer structures made solely out of amino acids) as cross-linkers (gelling agents) for hyaluronic acid. We discovered that the enzyme trypsin breaks down these gels, and that we can control the degradation rate of these hydrogels by changing the length and number of branches of the dendrimers. We also discovered we can use the same enzyme to transform a peptide from being non-responsive to cells to promoting their adhesion to it, and thus enabling their ability to survive in ECM-mimetic materials. These peptide dendrimers could find utility in drug delivery systems and in tissue engineering and regenerative medicine.