(645b) Photodegradable, Photoadaptable Hydrogels Via Radical-Mediated Disulfide Scission and Thiol-Ene Click Reaction

In the pursuit of novel and useful materials for the study and manipulation of tissue development, several schemes have been adopted to impart a biological responsiveness to synthetic hydrogels including, but not limited to, polyelectrolyte gels that swell and deswell with changes in pH,[1] thermosensitive gels that contract at physiologic temperatures[2] and peptide crosslinked hydrogels that degrade upon cleavage by cell-secreted enzymes.[3] While the exact motivations behind the development of various stimuli responsive materials are diverse, they share a general dependence on the biological context to which they are applied. Recently a paradigm shift has been effected by the introduction of photodegradable hydrogels, providing the user with exogenous control over the mechanical properties of the hydrogel in/on which cells are cultured and studied.[4] These hydrogels are crosslinked with monomers containing a photolabile nitrobenzyl ester, which may be lysed upon photon absorption. While the development of such materials has allowed researchers to probe cellular behavior under dynamic and discrete material mechanical modulation, light attenuation through the sample thickness, due to the strongly absorbing degradable moiety, limits the depth at which materials may be degraded.[5] Here we present a novel chemistry for photolabile hydrogels which overcomes the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels two millimeters thick within 50 seconds at low light intensities (10 mW/cm2, 365 nm). Hydrogels are formed by the oxidation of thiol functionalized 4-armed poly(ethylene glycol). This disulfide crosslinked hydrogel is swollen in a lithium acyl-phosphinate photoinitiator solution. Upon exposure to light at a wavelength of 365 nm, the radicals from the scission of the photoinitator attack and cleave the disulfides disintegrating the network. Addition of another component to this chemistry results in hydrogels that exhibit photoadaptation and healing. When a multifunctional norbornene is diffused into the hydrogel in the presence of a photoinitiator, thiyl radicals, liberated from the disulfide bond upon cleavage, react with the norbornenes to form thioethers. Thus, as disulfides are replaced with thioethers stress is alleviated and any strain applied to the polymer network is captured upon reaction completion or light exposure interruption. These materials are therefore capable of photomediated healing; two such hydrogels, swollen in initiator and norbornene solution and placed in direct contact anneal upon exposure to UV light. This novel but simple approach to photodegradable, photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the annealing of solid substrates (as opposed to the encapsulation by gelation of liquid media). Moreover, the principles and chemistry described herein hold implications for more than hydrogel materials but for photoadaptable polymers generally.

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