Rationally Designed Redox-Sensitive Protein Hydrogels\nwith Tunable Mechanical Properties

Abstract

Protein hydrogels are an important\nclass of materials for applications\nin biotechnology and medicine. The fine-tuning of their sequence,\nmolecular weight, and stereochemistry offers unique opportunities\nto engineer biofunctionality, biocompatibility, and biodegradability\ninto these materials. Here we report a new family of redox-sensitive\nprotein hydrogels with controllable mechanical properties composed\nof recombinant silk-elastin-like protein polymers (SELPs). The SELPs\nwere designed and synthesized with different ratios of silk-to-elastin\nblocks that incorporated periodic cysteine residues. The cysteine-containing\nSELPs were thermally responsive in solution and rapidly formed hydrogels\nat body temperature under physiologically relevant, mild oxidative\nconditions. Upon addition of a low concentration of hydrogen peroxide\nat 0.05% (w/v), gelation occurred within minutes for the SELPs with\na protein concentration of approximately 4% (w/v). The gelation time\nand mechanical properties of the hydrogels were dependent on the ratio\nof silk to elastin. These polymer designs also significantly affected\nredox-sensitive release of a highly polar model drug from the hydrogels\nin vitro. Furthermore, oxidative gelation was performed at other physiologically\nrelevant temperatures, and this resulted in hydrogels with tunable\nmechanical properties, thus, providing a secondary level of control\nover hydrogel stiffness. These newly developed injectable SELP hydrogels\nwith redox-sensitive features and tunable mechanical properties may\nbe potentially useful as biomaterials with broad applications in controlled\ndrug delivery and tissue engineering.