Enzymatic Regulation of Self-Assembling Peptide A9K2 Nanostructures and Hydrogelation with Highly Selective Antibacterial Activities

Hydrogels offer great potential for many biomedical and technological applications. For clinical uses, hydrogels that act as scaffold materials for cell culture, regenerative medicine, and drug delivery are required to have bactericidal properties. The amphiphilic peptide A(9)K(2) was designed to effectively inhibit bacterial growth via a mechanism of membrane permeabilization. The present study demonstrated that addition of fetal bovine serum (FBS) or plasma amine oxidase (PAO) induced a sol gel transition in A(9)K(2) aqueous solutions. The transformation of A(9)K(2) molecules catalyzed by lysyl oxidase (LO) in FBS or PAO accounted for the hydrogelation. Importantly, the enzymatic A(9)K(2) hydrogel displayed high antibacterial ability against both Gram-negative and Gram-positive bacterial strains while showing extremely low mammalian cell cytotoxicity, thus demonstrating good biocompatibility. Under established coculture conditions, the peptide hydrogel showed excellent selectivity by favoring the adherence and spreading of mammalian cells, while killing pathogenic bacteria, thus avoiding bacterial contamination. These advantages endow the enzymatic A(9)K(2) hydrogel with great potential for biomedical applications.