Self-Defensive Layer-by-Layer Films with Bacteria-Triggered Antibiotic Release

We report on highly efficient, bioresponsive, controlled-release antibacterial coatings constructed by direct assembly of tannic acid (TA) with one of several cationic antibiotics (tobromycin, gentamicin, and polymyxin B) using the layer-by-layer (LbL) technique. These films exhibit a distinct self-defense behavior triggered by acidification of the immediate environment by pathogenic bacteria, such as Staphylococcus epidermidis (S. epidermidis) or Escherichia coli (E coli). Films assembled using spin-assisted and dip-assisted techniques show drastically different morphology, thickness and pH-/bacteria-triggered antibiotic release characteristics. While dip-deposited films have rough surfaces with island like granular structures regardless of the film thickness, spin-assisted LbL assemblies demonstrate a transition from linear deposition of uniform 2D films to a highly developed 3D morphology for films thicker than similar to 45 nm. Ellipsometry, UV-vis and mass spectrometry confirm that all coatings do not release antibiotics in phosphate buffered saline at pH 7.4 for as long as one month in the absence of bacteria and therefore do not contribute to the development of antibiotic resistance. These films do, however, release antibiotics upon pH lowering. The rate of triggered release can be controlled through the choice of assembled antibiotic and the assembly technique (spin- vs dip-deposition) and by the spinning rate used during deposition, which all affect the strength of TA-antibiotic binding. TA/antibiotic coatings as thin as 40 nm strongly inhibit S. epidermidis and E coli bacterial growth both at surfaces and in surrounding medium, but support adhesion and proliferation of murine osteoblast cells. These coatings thus present a promising way to incorporate antibacterial agents at surfaces to prevent bacterial colonization of implanted biomedical devices.