(153e) Titanium Wires Modified By Peptoid-Loaded Microgels Resist S. Aureus Colonization

A wide range of surface-modification technologies continue to be explored to inhibit the bacterial colonization of synthetic surfaces with the aim of preventing infection associated with biomedical devices. We have been studying a self-defensive approach (1) where polyanionic microgels deposited electrostatically onto a synthetic surface are loaded with cationic antimicrobials which are later released upon exposure to bacterial triggering. We have previously demonstrated this process (2) with microgels based on poly(acrylic acid) [PAA] loaded with colistin or with an antimicrobial peptide. We are now exploring this concept using an antimicrobial peptoid known as TM1 (M_w=1819 Da, +5 charge). Peptoids are N-substituted glycines whose side chains are appended to the nitrogen rather than to the α-carbon of an amino acid (3). Here we study the complexation and sequestration properties of TM1 within PAA microgels synthesized by membrane emulsification coupled with free-radical (thermal or UV) polymerization. Complexation and sequestration can be followed using in situ optical microscopy to measure changes in the diameter of microgels immobilized on glass. When exposed to low-ionic-strength phosphate buffer containing dissolved TM1, the average microgel diameter rapidly decreases by ~60% due to osmotic effects associated with counterion release during TM1-PAA complexation and to the additional crosslinking caused by the polyvalent TM1 macro-ions. The average microgel diameter can remain unchanged for time scales of weeks when exposed to buffer (PBS) or culture medium, indicating that the TM1-PAA complexation is sufficiently strong to resist a burst release when exposed to physiological pH and ionic strength. We have challenged glass surfaces with S. epidermidis and used a PetriFilm assay to show that surfaces modified by TM1-loaded PAA microgels exhibit little or no subsequent bacterial growth while bacteria proliferate on unmodified control surfaces. We have furthermore developed an in vitro model of contamination within the operating room (OR) where bacteria can sediment from multiple sources - e.g. ventilation systems, shedding from clothing, staff sneezing/coughing, personnel traffic, etc. - onto exposed surfaces. As a substrate we used Ti wire typical of that used in an intermedullary rodent model and exposed wire samples to controlled bursts of aerosolized buffer containing known concentrations of viable methicillin-susceptible S. aureus. We studied Ti wires with four different treatments: unmodified, PAH-primed, (unloaded) microgel-modified, and TM1-loaded microgel-modified. Using assays to assess the presence and viability of both well-adhered and loosely bound bacteria, we find that TM1-loaded microgel-modified Ti wires effectively inhibit S. aureus colonization in this in vitro OR contamination model.

(1) X. Xiao, W. Zhao, J. Liang, K. Sauer, and M. Libera, Self-Defensive Antimicrobial Biomaterial Surfaces. Colloids and Surfaces B: Biointerfaces, 2020. DOI: 10.1016/j.colsurfb.2020.110989

(2) J. Liang, H. Wang, and M. Libera, Biomaterial Surfaces Self-Defensive against Bacteria by Contact Transfer of Antimicrobials.Biomaterials, 2019. 204(June): p. 25-35.

(3) N. Chongsiriwatana, R.N. Zuckermann, A.E. Barron, et al. Peptoids that Mimic the Structure, Function, and Mechanism of Helical Antimicrobial Peptides. Proc Natl Acad Sci U S A, 2008. 105(8): p. 2794-9.