Biocompatible Hybrid Organic/Inorganic Microhydrogels Promote Bacterial Adherence and Eradication in Vitro and in Vivo.

Self-assembling peptides and proteins have the potential to serve as multifunctional building blocks for the generation of versatile materials for a wide range of biomedical applications. In particular, supramolecular hydrogels comprised of self-assembled protein nanofibrils, have been used in contexts ranging from tissue engineering to drug delivery. Due to the rapid emergence of multidrug resistant bacteria, development of biomaterials with intrinsic antimicrobial properties has been continuously increasing. Here, we describe hybrid organic/inorganic nanofibrillar silk microgels decorated with silver nanoparticles that display potent antimicrobial activity in vitro and in vivo and are able to adhere bacterial cells to their surfaces while subsequently eradicating them, through a two-step mechanism of action. Importantly, in contrast to treatments involving conventional silver, these silk-silver microgels are nonhemolytic and noncytotoxic toward mammalian cell lines. Finally, we show that these hybrid microgels display substantial efficacy as topical antimicrobial agents in a murine model of surgical site infections.

Fabrication and Characterization of Reconstituted Silk Microgels for the Storage and Release of Small Molecules.

Silk fibroin is a natural protein obtained from the Bombyx mori silkworm. In addition to being the key structural component in silkworm cocoons, it also has the propensity to self-assemble in vitro into hierarchical structures with desirable properties such as high levels of mechanical strength and robustness. Furthermore, it is an appealing biopolymer due to its biocompatability, low immunogenicity, and lack of toxicity, making it a prime candidate for biomedical material applications. Here, it is demonstrated that nanofibrils formed by reconstituted silk fibroin can be engineered into supramolecular microgels using a soft lithography-based microfluidic approach. Building on these results, a potential application for these protein microgels to encapsulate and release small molecules in a controlled manner is illustrated. Taken together, these results suggest that the tailored self-assembly of biocompatible and biodegradable silk nanofibrils can be used to generate functional micromaterials for a range of potential applications in the biomedical and pharmaceutical fields.