Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrixes: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degrdn. of gels was engineered starting from a characterization of the degrdn. kinetics (kcat and Km) of synthetic MMP substrates in the sol. form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concn., and network crosslinking d. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of crit. defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 mg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrixes. These hydrogels may be useful in tissue engineering and cell biol. as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen. [on SciFinder (R)]