Appreciating the First Line of the Human Innate Immune Defense: A Strategy to Model and Alleviate the Neutrophil Elastase‐Mediated Attack toward Bioactivated Biomaterials

Biointerface engineering is a wide‐spread strategy to improve the healing process and subsequent tissue integration of biomaterials. Especially the integration of specific peptides is one promising strategy to promote the regenerative capacity of implants and 3D scaffolds. In vivo, these tailored interfaces are, however, first confronted with the innate immune response. Neutrophils are cells with pronounced proteolytic potential and the first recruited immune cells at the implant site; nonetheless, they have so far been underappreciated in the design of biomaterial interfaces. Herein, an in vitro approach is introduced to model and analyze the neutrophil interaction with bioactivated materials at the example of nano‐bioinspired electrospun surfaces that reveals the vulnerability of a given biointerface design to the contact with neutrophils. A sacrificial, transient hydrogel coating that demonstrates optimal protection for peptide‐modified surfaces and thus alleviates the immediate cleavage by neutrophil elastase is further introduced. An in vitro model is developed to mimic, control, and alleviate the neutrophil´s response toward covalently immobilized peptide moieties onto a nanofibrous material. While human neutrophil elastase (HNE) cleaves the peptide at an integrated HNE‐specific cleavage site, a strategy is presented to prevent this undesirable neutrophil response by embedding the biomaterial in a transient protective hydrogel layer during the HNE‐attack.