期刊
NATURE CHEMISTRY
卷 10, 期 3, 页码 251-258出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.2917
关键词
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资金
- NIH [S10 OD016240]
- University of Washington Faculty Startup Grant
- National Science Foundation CAREER Award [DMR 1652141]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007266] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD016240] Funding Source: NIH RePORTER
The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.
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