There is a need for coatings for biomedical devices and implants that can prevent the attachment of fungal pathogens while allowing human cells and tissue to appose without cytotoxicity. Here, the authors study whether a poly(2-hydroxyethylmethacrylate) (PHEMA) coating can suppress attachment and biofilm formation by Candida albicans and whether caspofungin terminally attached to surface-tethered polymeric linkers can provide additional benefits. The multistep coating scheme first involved the plasma polymerization of ethanol, followed by the attachment of α-bromoisobutyryl bromide (BiBB) onto surface hydroxyl groups of the plasma polymer layer. Polymer chains were grafted using surface initiated activators regenerated by electron transfer atom transfer radical polymerization with 2-hydroxyethylmethacrylate, yielding PHEMA layers with a dry thickness of up to 89 nm in 2 h. Hydroxyl groups of PHEMA were oxidized to aldehydes using the Albright–Goldman reaction, and caspofungin was covalently immobilized onto them using reductive amination. While the PHEMA layer by itself reduced the growth of C. albicans biofilms by log 1.4, the addition of caspofungin resulted in a marked further reduction by >4 log units to below the threshold of the test. The authors have confirmed that the predominant mechanism of action is caused by antifungal drug molecules that are covalently attached to the surface, rather than out-diffusing from the coating. The authors confirm the selectivity of surface-attached caspofungin in eliminating fungal, not mammalian cells by showing no measurable toxicity toward the myeloid leukaemia suspension cell line KG-1a.

1.
A. Y.
Peleg
,
D. A.
Hogan
, and
E.
Mylonakis
,
Nat. Rev. Microbiol.
8
,
340
(
2010
).
2.
B. R.
Coad
,
S. E.
Kidd
,
D. H.
Ellis
, and
H. J.
Griesser
,
Biotechnol. Adv.
32
,
296
(
2014
).
3.
L. J.
Douglas
,
Trends Microbiol.
11
,
30
(
2003
).
4.
G. D.
Brown
,
D. W.
Denning
,
N. A.
Gow
,
S. M.
Levitz
,
M. G.
Netea
, and
T. C.
White
,
Sci. Transl. Med.
4
,
165rv13
(
2012
).
5.
M. A.
Pfaller
and
D. J.
Diekema
,
Clin. Microbiol. Rev.
20
,
133
(
2007
).
6.
B. R.
Coad
,
S. J.
Lamont-Friedrich
,
L.
Gwynne
,
M.
Jasieniak
,
S. S.
Griesser
,
A.
Traven
,
A. Y.
Peleg
, and
H. J.
Griesser
,
J. Mater. Chem. B
3
,
8469
(
2015
).
7.
P.
Kingshott
,
J.
Wei
,
D.
Bagge-Ravn
,
N.
Gadegaard
, and
L.
Gram
,
Langmuir
19
,
6912
(
2003
).
8.
J. W.
Lussi
,
D.
Falconnet
,
J. A.
Hubbell
,
M.
Textor
, and
G.
Csucs
,
Biomaterials
27
,
2534
(
2006
).
9.
A. A.
Lazarin
,
A. L.
Machado
,
C. A.
Zamperini
,
A. F.
Wady
,
D. M. P.
Spolidorio
, and
C. E.
Vergani
,
Arch. Oral Biol.
58
,
1
(
2013
).
10.
T.
Bilgic
and
H. A.
Klok
,
Biomacromolecules
16
,
3657
(
2015
).
11.
O. R.
Homann
,
J.
Dea
,
S. M.
Noble
, and
A. D.
Johnson
,
PLoS Genet.
5
,
e1000783
(
2009
).
12.
K.
Werner
, “
RCA critical cleaning process
,”
2007
, http://www.microtechprocess.com/pdf/MTS_RCA.pdf.
14.
B. R.
Coad
,
T.
Scholz
,
K.
Vasilev
,
J. D.
Hayball
,
R. D.
Short
, and
H. J.
Griesser
,
ACS Appl. Mater. Interfaces
4
,
2455
(
2012
).
15.
B. R.
Coad
,
T.
Bilgic
, and
H.-A.
Klok
,
Langmuir
30
,
8357
(
2014
).
16.
J. D.
Albright
and
L.
Goldman
,
J. Am. Chem. Soc.
89
,
2416
(
1967
).
17.
S. S.
Griesser
,
M.
Jasieniak
,
B. R.
Coad
, and
H. J.
Griesser
,
Biointerphases
10
,
04A307
(
2015
).
18.
J.
Chandra
,
P. K.
Mukherjee
, and
M. A.
Ghannoum
,
Nat. Protoc.
3
,
1909
(
2008
).
19.
C. J.
Heilmann
,
A. G.
Sorgo
,
A. R.
Siliakus
,
H. L.
Dekker
,
S.
Brul
,
C. G.
de Koster
,
L. J.
de Koning
, and
F. M.
Klis
,
Microbiology
157
,
2297
(
2011
).
20.
K. S.
Siow
,
L.
Britcher
,
S.
Kumar
, and
H. J.
Griesser
,
Plasma Processes Polym.
3
,
392
(
2006
).
21.
R.
d'Agostino
,
P.
Favia
,
Y.
Kawai
,
H.
Ikegami
,
N.
Sato
, and
F.
Arefi-Khonsari
,
Advanced Plasma Technology
(
Wiley-VCH Verlag GmbH & Co.
,
2008
), pp.
I
XXII
.
22.
S.
Cheruthazhekatt
,
M.
Černák
,
P.
Slavíček
, and
J.
Havel
,
J. Appl. Biomed.
8
,
55
(
2010
).
23.
H. D.
Hazrati
,
J. D.
Whittle
, and
K.
Vasilev
,
Plasma Processes Polym.
11
,
149
(
2014
).
24.
L.
Xu
,
J.
Pan
,
J.
Dai
,
Z.
Cao
,
H.
Hang
,
X.
Li
, and
Y.
Yan
,
RSC Adv.
2
,
5571
(
2012
).
25.
X.
Wang
,
X.
Xiao
,
X.
Wang
,
J.
Zhou
,
L.
Li
,
J.
Xu
, and
B.
Guo
,
Macromol. Rapid Commun.
28
,
828
(
2007
).
26.
X.
Dong
,
H.
Bao
,
K.
Ou
,
J.
Yao
,
W.
Zhang
, and
J.
He
,
Fibers Polym.
16
,
1478
(
2015
).
27.
C.
Gao
,
C. D.
Vo
,
Y. Z.
Jin
,
W.
Li
, and
S. P.
Armes
,
Macromolecules
38
,
8634
(
2005
).
28.
Y. K.
Jhon
,
S.
Arifuzzaman
,
A. E.
Özçam
,
A. D. J.
Kiserow
, and
J.
Genzer
,
Langmuir
28
,
872
(
2012
).
29.
S.
Tugulu
,
P.
Silacci
,
N.
Stergiopulos
, and
H.-A.
Klok
,
Biomaterials
28
,
2536
(
2007
).
30.
J.
Sha
,
Y.
Gao
,
T.
Wu
,
X.
Chen
,
T.
Cordie
,
H.
Zhao
,
L.
Xie
,
Y.
Ma
, and
L.-S.
Turng
,
RSC Adv.
6
,
35641
(
2016
).
31.
D.
Keskin
,
J. I.
Clodt
,
J.
Hahn
,
V.
Abetz
, and
V.
Filiz
,
Langmuir
30
,
8907
(
2014
).
32.
S. M.
Paterson
,
D. H.
Brown
,
T. V.
Chirila
,
I.
Keen
,
A. K.
Whittaker
, and
M. V.
Baker
,
J. Polym. Sci., Part A
48
,
4084
(
2010
).
33.
C. H.
Worthley
,
K. T.
Constantopoulos
,
M.
Ginic-Markovic
,
R. J.
Pillar
,
J. G.
Matisons
, and
S.
Clarke
,
J. Membr. Sci.
385–386
,
385
(
2011
).
34.
R.
Barbey
,
L.
Lavanant
,
D.
Paripovic
,
N.
Schuwer
,
C.
Sugnaux
,
S.
Tugulu
, and
H. A.
Klok
,
Chem. Rev.
109
,
5437
(
2009
).
35.
N.
Katagiri
,
H.
Akatsuka
,
T.
Haneda
,
C.
Kaneko
, and
A.
Sera
,
J. Org. Chem.
53
,
5464
(
1988
).
36.
A. B.
Smith
and
H.
Cui
,
Org. Lett.
5
,
587
(
2003
).
37.
J.
Mora-Duarte
 et al.,
New Engl J Med.
347
,
2020
(
2002
).
38.
M.
Jasieniak
,
B. R.
Coad
, and
H. J.
Griesser
,
Biointerphases
10
,
04A310
(
2015
).
39.
S.
Kucharíková
 et al.,
J. Antimicrob. Chemother.
71
,
936
(
2016
).
40.
A.
Braem
 et al.,
ACS Appl. Mater. Interfaces
9
,
8533
(
2017
).
41.
T. D.
Michl
,
C.
Giles
,
A. T.
Cross
,
H. J.
Griesser
, and
B. R.
Coad
,
RSC Adv.
7
,
27678
(
2017
).
42.
S.
El-Kirat-Chatel
,
A.
Beaussart
,
D.
Alsteens
,
D. N.
Jackson
,
P. N.
Lipke
, and
Y. F.
Dufrene
,
Nanoscale
5
,
1105
(
2013
).
43.
T. J.
Walsh
 et al.,
Antimicrob. Agents Chemother.
49
,
4536
(
2005
).
44.
A.
Paulitsch
,
W.
Weger
,
G.
Ginter-Hanselmayer
,
E.
Marth
, and
W.
Buzina
,
Mycoses
49
,
471
(
2006
).
45.
J. P.
Martinez
,
M. L.
Gil
,
J. L.
Lopez-Ribot
, and
W. L.
Chaffin
,
Clin. Microbiol. Rev.
11
,
121
(
1998
).
46.
A.
Safdar
,
T. W.
Bannister
, and
Z.
Safdar
,
Int. J. Infect. Dis.
8
,
180
(
2004
).
47.
G. S.
Baillie
and
L. J.
Douglas
,
Antimicrob. Agents Chemother.
42
,
1900
(
1998
).
48.
J.
Chandra
,
J. D.
Patel
,
J.
Li
,
G.
Zhou
,
P. K.
Mukherjee
,
T. S.
McCormick
,
J. M.
Anderson
, and
M. A.
Ghannoum
,
Appl. Environ. Microbiol.
71
,
8795
(
2005
).
49.
J.
Chandra
,
D. M.
Kuhn
,
P. K.
Mukherjee
,
L. L.
Hoyer
,
T.
McCormick
, and
M. A.
Ghannoum
,
J. Bacteriol.
183
,
5385
(
2001
).
50.
A.
Roosjen
,
H. J.
Kaper
,
H. C.
van der Mei
,
W.
Norde
, and
H. J.
Busscher
,
Microbiology
149
,
3239
(
2003
).
51.
M.
Stefani
,
J.
Coudane
, and
M.
Vert
,
Polym. Degrad. Stab.
91
,
2554
(
2006
).
52.
A. D.
Marshall
,
P. A.
Munro
, and
G.
Tragardh
,
Desalination
91
,
65
(
1993
).
54.
H. P.
Koeffler
,
Blood
62
,
709
(
1983
).
55.
M. R.
Koller
,
S. G.
Emerson
, and
B. O.
Palsson
,
Blood
82
,
378
(
1993
).
56.
M. I.
Garin
,
J. F.
Apperley
, and
J. V.
Melo
,
Eur. J. Haematol.
64
,
85
(
2000
).
57.
H.
Mirzadeh
,
M. T.
Khorasani
,
A. A.
Katbab
,
R. P.
Burford
,
Z.
Soheili
,
A.
Golestani
, and
B.
Goliaei
,
Clin. Mater.
16
,
177
(
1994
).
58.
G.-H.
Hsiue
,
J.-M.
Yang
, and
R.-L.
Wu
,
J. Biomed. Mater. Res.
22
,
405
(
1988
).
59.
M.
Alishiri
,
A.
Shojaei
, and
M. J.
Abdekhodaie
,
RSC Adv.
6
,
8743
(
2016
).
60.
E.
Ruoslahti
,
Annu. Rev. Cell. Dev. Biol.
12
,
697
(
1996
).
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