期刊
ADVANCED MATERIALS
卷 31, 期 33, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201902462
关键词
Boolean logic; degradation; hydrogels; protein delivery; sortase
类别
资金
- National Institutes of Health [S10 OD016240]
- University of Washington Faculty Startup Grant
- National Science Foundation [DMR 1652141, DMR 1807398]
The controlled presentation of proteins from and within materials remains of significant interest for many bioengineering applications. Though smart platforms offer control over protein release in response to a single external cue, no strategy has been developed to trigger delivery in response to user-specified combinations of environmental inputs, nor to independently control the release of multiple species from a homogenous material. Here, a modular semisynthetic scheme is introduced to govern the release of site-specifically modified proteins from hydrogels following Boolean logic. A sortase-mediated transpeptidation reaction is used to generate recombinant proteins C-terminally tethered to gels through environmentally sensitive degradable linkers. By varying the connectivity of multiple stimuli-labile moieties within these customizable linkers, YES/OR/AND control of protein release is exhaustively demonstrated in response to one and two-input combinations involving enzyme, reductant, and light. Tethering of multiple proteins each through a different stimuli-sensitive linker permits their independent and sequential release from a common material. It is expected that these methodologies will enable new opportunities in tissue engineering and therapeutic delivery.
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