Engineering the NET-biomaterial interface to treat disease

Neutrophil extracellular traps (NETs) are matrices composed of DNA and antimicrobial proteins that are released from neutrophils to entrap and degrade pathogens. Overproduction of these biological networks can induce hyperinflammation in infectious diseases and autoimmune disorders and exacerbate cancer metastasis formation. Systemic administration of immunosuppressive therapeutics and NET-degrading drugs can have adverse side effects, underscoring the importance of creating controlled release formulations to target NETs. In this review, we discuss the NET-biomaterial interface for drug delivery to address infection, inflammation, and cancer. First, we examine how drug delivery platforms can be engineered for localized delivery of NET-modulating or NET-degrading drugs. Then, we consider a class of NET-inspired materials that can replicate NET function and pathogen degradation without triggering downstream hyperinflammation. Finally, we discuss current challenges in the field and how biomaterials can be further developed to elucidate fundamental insights on NET biology and target NET dysregulation in various disease states.