Abstract: Various embodiments are described herein for the fabrication enzyme degradable hydrogels useful as payload delivery systems. More particularly, embodiments disclosed herein relate to enzyme-degradable hydrogel systems comprising a crosslinkable polymer, such as a chemically-modified biopolymer, for example, chemically-modified gelatin, the hydrogel formed by a method comprising sequential physical and chemical crosslinking steps, for delivery of various payloads. Enzymes may be selected and administered to tune the release profile of the hydrogel. The payload can be, but not limited to, drugs, markers, cells, or these members encapsulated within another drug delivery such as a nanoparticle, or liposome. The hydrogel system can also be combined with another device such as a contact lens or bandage for wound healing.