Photoselective Delivery of Model Therapeutics from Hydrogels

Hydrogels are commonly used in biomedical applications to sequester and release therapeutics. Covalently tethering therapeutic agents to a hydrogel through a degradable linkage allows their controlled release, but temporally separating the release of multiple therapeutics from a single hydrogel remains a major challenge. In this report, we use a series of photodegradable ortho-nitrobenzyl (o-NB) groups with varying structures to link model therapeutic agents (fluorescein, rhodamine, and aminomethylcoumarin acetate) to poly(ethylene glycol) macromers. We polymerized the macromers into hydrogel networks via redox polymerization and quantified the apparent rate constants of degradation (k(app)) of each of the photoreleasable compounds. By exploiting differences in reactivity of the different o-NB groups, we are able to create complex, multistage release profiles. We demonstrate the ability to switch between concurrent and biased release of model therapeutics simply by switching wavelengths. We also demonstrate a complex four-stage release profile in which the release of three separate model therapeutics is controlled by varying wavelength, intensity, and exposure time. This is the first report of photoselective release of therapeutics from a hydrogel, allowing user-dictated real-time spatial and temporal control over multiple chemical signals in a cell microenvironment in 2D and 3D.