Thermally Responsive Collagen Switching from Bactericidal for Ambient Storage Condition to Biologically Inert in Vivo

Abstract

Incorporating preservatives is now the most commonlyemployed strategy to prevent microbial deterioration of collagen.However, many preservatives are non-selective; they cannotdifferentiate the orthologs in mammalian cells from theirbiological targets in pathogens, and thus their incorporationcompromises the inherent biocompatibility of naturallyoccurring collagen. Here, we report a strategy to covalentlyanchor antibacterial agents to collagen via a thermally responsivepoly(N-isopropylacrylamide) spacer. As the spacer suddenlycollapses from an extended coil upon heating through ~30°C,bioactivity of the anchored antibacterial agents can be switchedoff, because their lateral mobility and, hence, target-siteaccessibility are restricted. Accordingly, the modified collagencan be preserved without microbial deterioration for ambientstorage condition, while imposing no cytotoxic impact uponsurrounding tissues in vivo. This thermally responsive collagenholds great potential in biomedical fields, where the collagenproducts are intended to have intimate contact with humantissues or be administered parenterally.