Wound infections originate when exogenous or endogenous bacterial pathogens can circumvent the barrier of the wound dressing and invade the wound bed. Bacterial colonization causes inflammation, stalls the healing process, and carries the risk of dissemination to other tissues. In addition, current antimicrobial dressings fail to resolve an infection once it has been established because debris of the killed bacteria rapidly accumulates on their surface and hampers the antimicrobial action. Faced with this challenge, hybrid synthetic‐natural water‐soluble macromolecules are designed that self‐assemble onto the surface of dressings to generate an antifouling brush functionalized with endolysin, a bactericidal enzyme that poses no harm for eukaryotic cells. The simultaneous action of the brush and the enzyme not only prevents the colonization of the dressing, but also enables the coating to kill planktonic bacteria with even higher efficiency than the free enzyme. Remarkably, the Kill&Repel coating could completely eradicate bacteria in a simulated infection without allowing the adhesion of residues on the surface. Thus, this strategy opens a revolutionary approach for protecting and treating an infected wound in a safer and more efficient manner.
Nature utilizes endothelium
as a blood interface that perfectly
controls hemostasis, preventing the uncontrolled formation of thrombi.
The management of positive and negative feedback that finely tunes
thrombosis and fibrinolysis is essential for human life, especially
for patients who undergo extracorporeal circulation (ECC) after a
severe respiratory or cardiac failure. The exposure of blood to a
surface different from healthy endothelium inevitably initiates coagulation,
drastically increasing the mortality rate by thromboembolic complications.
In the present study, an ultrathin antifouling fibrinolytic coating
capable of disintegrating thrombi in a self-regulated manner is reported.
The coating system is composed of a polymer brush layer that can prevent
any unspecific interaction with blood. The brushes are functionalized
with a tissue plasminogen activator (tPA) to establish localized fibrinolysis
that solely and exclusively is active when it is required. This interactive
switching between the dormant and active state is realized through
an amplification mechanism that increases (positive feedback) or restores
(negative feedback) the activity of tPA depending on whether a thrombus
is detected and captured or not. Thus, only a low surface density
of tPA is necessary to lyse real thrombi. Our work demonstrates the
first report of a coating that self-regulates its fibrinolytic activity
depending on the conditions of blood.
Interfacing artificial materials with biological tissues remains a challenge. The direct contact of their surface with the biological milieu results in multiscale interactions, in which biomacromolecules adsorb and act as transducers mediating the interactions with cells and tissues. So far, only antifouling polymer brushes have been able to conceal the surface of synthetic materials. However, their complex synthesis has precluded their translation to applications. Here, it is shown that ultrathin surface-attached hydrogel coatings of N-(2-hydroxypropyl) methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA) provide the same level of protection as brushes. In spite of being readily applicable, these coatings prevent the fouling from whole blood plasma and provide a barrier to the adhesion of Gram positive and negative bacteria. The analysis of the components of the surface free energy and nanoindentation experiments reveals that the excellent antifouling properties stem from the strong surface hydrophilicity and the presence of a brush-like structure at the water interface. Moreover, these coatings can be functionalized to achieve antimicrobial activity while remaining stealth and non-cytotoxic to eukaryotic cells. Such level of performance is previously only achieved with brushes. Thus, it is anticipated that this readily applicable strategy is a promising route to enhance the biocompatibility of real biomedical devices.
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