A shortage of available organ donors
has created a need for engineered
tissues. In this context, polymer-based hydrogels that break down
inside the body are often used as constructs for growth factors and
cells. Herein, we report imine cross-linked gels where degradation
is controllable by the introduction of mixed imine cross-links. Specifically,
hydrazide-functionalized poly(ethylene glycol) (PEG) reacts with aldehyde-functionalized
PEG (PEG-CHO) to form hydrazone linked hydrogels that degrade quickly
in media. The time to degradation can be controlled by changing the
structure of the hydrazide group or by introducing hydroxylamines
to form nonreversible oxime linkages. Hydrogels containing adipohydrazide-functionalized
PEG (PEG-ADH) and PEG-CHO were found to degrade more rapidly than
gels formed from carbodihydrazide-functionalized PEG (PEG-CDH). Incorporating
oxime linkages via aminooxy-functionalized PEG (PEG-AO) into the hydrazone
cross-linked gels further stabilized the hydrogels. This imine cross-linking
approach should be useful for modulating the degradation characteristics
of 3D cell culture supports for controlled cell release
