Logic‐Based Delivery of Site‐Specifically Modified Proteins from Environmentally Responsive Hydrogel Biomaterials

• Published in: Advanced materials (Weinheim) Vol. 31; no. 33; pp. e1902462 - n/a
• Main Authors: Gawade, Prathamesh Milind, Shadish, Jared A., Badeau, Barry A., DeForest, Cole A.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2019
• Subjects: Bioengineering; Biomedical materials; Boolean algebra; Boolean logic; degradation; Gels; Hydrogels; protein delivery; Proteins; sortase; Stimuli; Tethering; Tissue engineering; degradation; hydrogels; Boolean logic; protein delivery; sortase
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.201902462

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. The programmed release of site‐specifically modified proteins from hydrogel biomaterials in response to precise combinations of environmental inputs is specified using Boolean YES/OR/AND logic. Sequential and independently controlled release of proteins from a common material is afforded through well‐defined installation of degradable moieties tethering the protein to the gel.