β-Lactamase Responsive Supramolecular Hydrogels with Host–Guest Self-Healing Capability

Smart supramolecular materials have gained popularity for a range of applications, including sensing, drug delivery, and tissue engineering. In this work, we describe a “host–guest” supramolecular hydrogel formulated with a bifunctional guest complex. Polymeric cyclodextrin (PCD) was utilized as the host backbone of the hydrogel, which was reinforced with an interpenetrating network polymerized by acrylamide/N-vinylpyrrolidinone. The guest molecule developed here was designed to not only enable molecular association with PCD, imparting hydrogels with a self-healing capability, but also undergo enzymatic cleavage, causing macroscale degradation of the hydrogel. This dual functional behavior was obtained by incorporation of two adamantane (AD) moieties on the guest, which form cross-links between the PCD hydrophobic cavities and a β-lactam core, which is cleaved by bacteria produced β-lactamases (βLs). The supramolecular host–guest hydrogels underwent self-healing upon severing and were able to regain an initial tensile modulus comparable to that of the as-formed hydrogels within ∼20 h. The hydrogels were also found to remain stable at simulated physiological conditions (phosphate buffered saline, pH 7.4, 37 °C) and degrade specifically in the presence of βLs from Bacillus cereus and Enterobacter cloacae over 28–35 h. Hydrogels with a protecting group attached to a common βL recognition site on the guest exhibited a significantly slower degradation, confirming that hydrogel degradation is specific to βL cleavage of the guest molecule. This βL responsive degradation was translated to bacteria, resulting in complete degradation of hydrogels incubated with cultures of βL producing bacteria in approximately 72 h, while those incubated with non-βL producing bacteria remained stable over this time. The supramolecular host–guest hydrogels developed here are promising for future applications of bacteria-responsive materials, including controlled drug delivery and diagnostics, in which a robust material capable of self-healing is desirable.