Logical Control over Biomaterial Properties through Boolean Responsive Linkers
Badeau, Barry Alick
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Medicine is fundamentally constrained by our ability to manipulate the levers and gears of biology—cells, genes, and proteins. Typical approaches, including systemic therapeutic administration and surgery, lack the precision required to effectively treat certain diseases. Biomaterials that dynamically sense and respond to critical aspects of their environment could enable new possibilities in targeted drug delivery, diagnostics, cell culture and regenerative medicine. However, there is not yet a framework for creating materials responsive to multiple inputs in a well-defined manner. This dissertation details the development of a modular biomaterial platform that can integrate multiple biochemical inputs to provide a functional output through Boolean computation. The connectivity and architecture of multiple stimuli-labile groups incorporated into a single linker determines its behavior upon the environmentally triggered cleavage of combinations of these moieties. To validate this framework we employed, light, reductant, and enzyme as inputs to create seventeen unique logically degradable hydrogels. The Boolean linkers were then used to govern the release of pendant proteins, small molecules, and therapeutics from non-degradable hydrogels. Finally, we exploited this system to enable logic-triggered activation of cell-penetrating peptides to regulate the cellular uptake of proteins. This modular platform offers unprecedented control over biomaterial performance in complex biological environments. By enabling the creation of materials tailored to application-specific needs, it could unlock new possibilities in science and medicine.
- Chemical engineering