Logic-Based Delivery of Site-Specifically-Modified Proteins from Gels through Engineered Biomacromolecular Architecture

Abstract

Stimuli-responsive behavior has been widely used to design hydrogels for the delivery of therapeutic proteins. However, these delivery platforms are often restricted to a single programmed stimulus. Designing a simple, modular system which can deliver multiple proteins in response to multiple external cues still remains a challenge. In this work, we have built stimuli-degradable peptide linkers programmed with Boolean logic gates (YES/OR/AND). Through our logic-programmed peptide linkers, we demonstrate the ability to tether a variety of proteins to the hydrogel network and release these proteins in response to user-specified combination of different environmental stimuli. Utilizing this approach, we have shown that different proteins can be independently and differentially released from the same hydrogel. We believe that our system will provide the ability to exploit new opportunities in protein delivery and tissue culture application.