Hydrogels are used to study cell differentiation and tissue evolution, where it is critical to be able to deliver chemical cues in a spatially and temporally defined manner. Covalently tethering therapeutic agents into a hydrogel through a degradable linkage allows their predictable and controlled release. Hydrolyzable and enzymatically degradable linkages have been reported, but lack external control. In contrast, photodegradation is externally controlled, allowing user-dictated release.  We synthesized and characterized macromers with photodegradbale ortho-nitrobenzyl groups incorporating activated disulfides, and copolymerized them into hydrogel depots, allowing post-polymerization conjugation of thiol-containing proteins via disulfide exchange. Using this approach, we fabricated hydrogels depots with photoreleasable lysozyme and bovine serum albumin.  While lysozyme is easily incorporated within 24 h, BSA is unable to undergo disulfide exchange even after 48 h.  Since BSA readily diffuses into and out of the hydrogel, this indicates that sterics play an important role in conjugating proteins to these hydrogels.

Steric effects in protein loading and photorelease from hydrogel depots

244th National Meeting (2012)

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