ARTICLE pubs.acs.org/Macromolecules Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction Benjamin D. Fairbanks,†,§ Samir P. Singh,† Christopher N. Bowman,† and Kristi S. Anseth*,†,‡ †Department of Chemical and Biological Engineering and ‡ Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309-0424, United States ABSTRACT: Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manip- ulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemi- cally deform and degrade disulﬁde cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm2 at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulﬁde cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulﬁde exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally. ’ INTRODUCTION Covalently cross-linked hydrogels represent an important class of biomedical materials as tools for localized drug delivery as well as for the encapsulation of cells for manipulating critical cellular functions and/or tissue development. Covalently cross- linked gels are often formed via the reaction of multifunctional and high molecular weight hydrophilic macromolecules, includ- ing proteins, polysaccharides, or synthetic polymers such as poly(ethylene glycol) (PEG), through a variety of polymerization reactions including chain growth (meth)acrylate polymerization,1 Michael addition,2 azide alkyne cycloaddition,3,4 radical thiol ene photopolymerization,5 and oxidation of thiols to disulﬁdes.6 8 Of particular interest in recent years are hydrogels that exhibit some chemical and/or physical change in response to an external stimulus. By virtue of their dynamic behavior, many such stimuli- responsive hydrogels, sometimes referred to as “smart” hydro- gels, have been applied to drug delivery and tissue engineering in attempts to both permit and control mass transport and/or cellular interaction with(in) the material. Various approaches have been adopted to impart a biological responsiveness to synthetic hydrogels including, but not limited to, oxygen-sensi- tive disulﬁde polymerization mentioned previously, polyelectro- lyte gels that swell and deswell with changes in pH,9 thermoresponsive gels that form or contract at physiological temperatures,10 and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes.2 Chemistry and applications vary among the diﬀerent stimuli-responsive materi- als though most share a general dependence on the biological context in which they are placed; most often it is the biological context that stimulates the material’s response. Recently, an innovative approach to stimuli-responsive hydrogels was re- ported wherein the user, and not the biological context, provides the stimulus that elicits the materials’ response.11 13 These synthetic, polymeric hydrogels were cross-linked with multi- functional monomers containing a photolabile nitrobenzyl ester, which lyses upon photon absorption, providing the user with exogenous control of material degradation and numerous other material properties. While the development of such materials has allowed re- searchers to probe cellular behavior under dynamic and discrete modulation, the strongly absorbing nitrobenzene moiety limits the depth to which materials may be degraded and also repre- sents an irreversible change in the structure that prevents conservation of the mechanical properties and/or cross-link density.12 To overcome this latter limitation, hydrogels cross-linked with trithiocarbonate-containing monomers have been synthesized that, through addition and fragmentation reactions, reversibly Received: Revised: Published: January 28, 2011 March 3, 2011 March 16, 2011 r 2011 American Chemical Society 2444 dx.doi.org/10.1021/ma200202w | Macromolecules 2011, 44, 2444–2450