Peptoid‐Loaded Microgels Self‐Defensively Inhibit Staphylococcal Colonization of Titanium in a Model of Operating‐Room Contamination

Abstract

Bacterial contamination of an exposed implantable medical device by the atmosphere of an operating room (OR) is increasingly implicated as a cause of device‐associated infection. Here, OR contamination is modeled in vitro using an aerosolizing system to spray small quantities of staphylococci onto titanium rods. Contaminated rods always manifest culturable bacteria. Self‐assembly is used to create a self‐defensive Ti surface that substantially enhances the rod's resistance to such contamination. Poly(acrylic acid) microgels are electrostatically deposited onto small Ti rods and subsequently loaded by complexation with a cationic antimicrobial peptoid (TM1). The microgels are visualized in situ by optical microscopy, and changes in microgel diameter indicate the loading state. These measurements show that TM1 can be quickly loaded from low‐ionic‐strength buffer and subsequently remained sequestered within the microgels for up to 4 weeks when soaked in phosphate buffered saline. TM1‐loaded microgel‐modified Ti surfaces are contaminated with aerosolized staphylococci, and subsequent assays indicate few or no culturable bacteria. In the absence of nutrients to enable metabolism, this finding suggests that bacteria trigger local TM1 release by contact transfer. The modified surfaces exhibit good in vitro cytocompatibility as manifested by the adhesion, spreading, and metabolic activity of human fetal osteoblasts. An in vitro model of operating‐room contamination shows that the staphylococcal colonization of a titanium rod is prevented by modifying the Ti surface with a sub‐monolayer of poly(acrylic acid) microgels loaded by complexation with a cationic antimicrobial peptoid (TM1). Self‐defensive bacteria‐triggered peptoid release occurs by contact transfer. The modified surface remains cytocompatable, and osteoblasts do not trigger TM1 release.

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2201662 (1 of 9) ©  Wiley-VCH GmbH
Peptoid-Loaded Microgels Self-Defensively Inhibit
Staphylococcal Colonization of Titanium in a Model of
Operating-Room Contamination
Wenhan Zhao, Haoyu Wang, Xixi Xiao, Lauren De Stefano, Jordan Katz, Jennifer S. Lin,
Annelise E. Barron, Thomas P. Schaer, Hongjun Wang, and Matthew Libera*
DOI: 10.1002/admi.202201662
within and in/out of the room itself.[]
These airborne bacteria can accumulate
on the surface of an implantable bio-
medical device once it is removed from
its sterile package. Early measurements[]
reported a bacterial surface-accumulation
rate of ≈ ×  CFU m− h−. Increased
and improved practices of infection con-
trol have steadily reduced that rate. More
recent studies report rates ranging from
 to  CFU m− h−.[] These rates sug-
gest that devices are being implanted after
they have been contaminated by hundreds
or thousands of bacteria. Once implanted
and exposed to favorable growth condi-
tions within the body, a subset of these
bacteria can develop into biofilms and lead
to chronic device-associated infection.
Devices such as hip/knee prostheses,[]
heart valves,[] pacemakers,[] cochlear
implants,[] shunts,[] surgical mesh,[]
sutures,[] tissue-engineering con-
structs,[] among many others, are sus-
ceptible to device-associated infection.
The fact that the incidence of surgical site
infection increases linearly with time in the OR is well estab-
lished,[] and there is strong consensus that intraoperative con-
tamination is responsible for at least some device-associated
infections.[]
Self-defensive surfaces[] represent an emerging and
compelling strategy that may be able to inhibit bacterial
colonization due to OR contamination. The term self-defensive
Bacterial contamination of an exposed implantable medical device by the
atmosphere of an operating room (OR) is increasingly implicated as a cause
of device-associated infection. Here, OR contamination is modeled in vitro
using an aerosolizing system to spray small quantities of staphylococci
onto titanium rods. Contaminated rods always manifest culturable bacteria.
Self-assembly is used to create a self-defensive Ti surface that substantially
enhances the rod’s resistance to such contamination. Poly(acrylic acid) micro-
gels are electrostatically deposited onto small Ti rods and subsequently loaded
by complexation with a cationic antimicrobial peptoid (TM1). The microgels
are visualized in situ by optical microscopy, and changes in microgel diameter
indicate the loading state. These measurements show that TM1 can be quickly
loaded from low-ionic-strength buer and subsequently remained sequestered
within the microgels for up to 4 weeks when soaked in phosphate buered
saline. TM1-loaded microgel-modified Ti surfaces are contaminated with aero-
solized staphylococci, and subsequent assays indicate few or no culturable
bacteria. In the absence of nutrients to enable metabolism, this finding sug-
gests that bacteria trigger local TM1 release by contact transfer. The modified
surfaces exhibit good in vitro cytocompatibility as manifested by the adhesion,
spreading, and metabolic activity of human fetal osteoblasts.
W. Zhao, X. Xiao, M. Libera
Department of Chemical Engineering and Materials Science
Stevens Institute of Technology
Hoboken, NJ , USA
E-mail: mlibera@stevens.edu
H. Wang, H. Wang
Department of Biomedical Engineering
Stevens Institute of Technology
Hoboken, NJ , USA
L. De Stefano, J. Katz
Orthobond Corporation
Princeton, NJ , USA
J. S. Lin, A. E. Barron
Department of Bioengineering
School of Medicine
Stanford University
Stanford, CA , USA
T. P. Schaer
Department of Clinical Studies
New Bolton Center
School of Veterinary Medicine
University of Pennsylvania
Kennett Square, PA , USA
ReseaRch aRticle
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/./admi..
1. Introduction
Despite the fact that the surgical operating room (OR) is com-
monly referred to as sterile or aseptic, the OR atmosphere in
reality contains microbes from many sources. Among them
are ventilation systems, shedding from clothing, sneezing or
coughing by OR personnel, as well as pedestrian trac both
Adv. Mater. Interfaces 2022, 9, 