Natural defenses against infection combine direct microbial killing with physical attributes, such as the barrier formed by intact skin. When these defenses are compromised by surgery or trauma, there is a need to replace both of these components until healing occurs.

Bevilacqua et al. report a biopolymer that provides dual functionality of both a potent microbicide and effective physical barrier. Designed for local application to exposed tissues, the reported biopolymer, designated K₁₀₀L₄₀, is amino acid based. It contains water soluble and water insoluble domains composed of a positively-charged segment made of lysine amino acids, and a hydrophobic segment made of leucine amino acids. While having the composition of a simple protein, K₁₀₀L₄₀ is produced using inexpensive and scalable methods similar to those used to make plastics, rather than traditional peptide solid phase synthesis or protein biosynthetic methods.

Long-chain amino acid block copolymer of sequence poly(L-lysine·hydrochloride)100- b-poly(L-leucine)40 (K100L40).

K₁₀₀L₄₀ was shown to be broadly antimicrobial, with rapid and potent activity against gram-positive and gram-negative bacteria, as well as yeast, including multidrug-resistant (MDR) strains. Notably, activity was demonstrated against S. aureus, methicillin-resistant S. aureus (MRSA), vancomycin-resistant E. faecium, A. baumannii (including MDR), P. aeruginosa (including MDR), carbapenem-resistant Enterobacteriaceae (CRE), and C. albicans (including fluconazole-resistant), all of which cause substantial morbidity and mortality in healthcare settings today.

Driven by the association of water insoluble segments, K₁₀₀L₄₀ biopolymers form viscous solutions and self-supporting, three dimensional hydrogel networks at low concentrations in water. These physical characteristics of K₁₀₀L₄₀ preparations provide an effective barrier to microbial contamination, as measured by substantial decreases of tissue-associated bacteria after deliberate inoculation of porcine skin explants. These preparations were also shown to be effective in porcine open wounds and rodent closed wounds containing a foreign implant in vivo.

Based on these findings, synthetic biopolymers with the features of K₁₀₀L₄₀ were shown to be a promising new approach for prevention of wound infections by combining potent, direct antimicrobial activity and physical barrier properties in a single component material.