State-of-the-Art, and Perspectives of, Silver/Plasma Polymer Antibacterial Nanocomposites

17 Pages·2017·3.23 MB·English

antibiotics
Review
State-of-the-Art, and Perspectives of, Silver/Plasma
Polymer Antibacterial Nanocomposites
JirˇíKratochvíl ID,AnnaKuzminovaandOndrˇejKylián* ID
DepartmentofMacromolecular,FacultyofMathematicsandPhysics,PhysicsCharlesUniversity,
Prague18000,CzechRepublic;[email protected](J.K.);[email protected](A.K.)
* Correspondence:[email protected];Tel.:[phone]
(cid:1)(cid:2)(cid:3)(cid:1)(cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:1)
(cid:1)(cid:2)(cid:3)(cid:4)(cid:5)(cid:6)(cid:7)
Received:14July2018;Accepted:10August2018;Published:17August2018
Abstract: Urgent need for innovative and effective antibacterial coatings in different fields
seems to have triggered the development of numerous strategies for the production of such
materials. Asshowninthisshortoverview,plasmabasedtechniquesarouseconsiderableattention
that is connected with the possibility to use these techniques for the production of advanced
antibacterial Ag/plasma polymer coatings with tailor-made functional properties. In addition,
theplasma-baseddepositionisbelievedtobewell-suitedfortheproductionofnovelmulti-functional
orstimuli-responsiveantibacterialfilms.
Keywords: non-equilibriumplasma;silver;antibacterialcoatings;plasmapolymers;nanocomposites
1. Introduction
Asshowninnumerousrecentreviews,road-maps,and“white”papers[1–7],non-equilibrium
plasmasmaybesuccessfullyusedinvariousfields,suchasfromtheautomotiveoraerospaceindustry
towaste andpollutioncontrol, orfrom theproduction ofadvancedfunctional biomaterials tothe
designofsmarttextiles. Thetremendousboomthatplasma-basedtechnologiesexperiencedinthelast
fewdecadesismainlygivenbytheiruniquefeatures. Thesecomprisearelativelylow-temperature
natureoftheprocessesthatemployplasma,allowingprocessingofheat-sensitivematerials,including
polymers, to treat or coat virtually any material without compromising the bulk properties of
treated objects or high versatility in terms of materials that may be deposited by plasma-based
techniques(e.g.,metals,metal-oxides,plasmapolymers).Incontrasttotechniquesthatutilizechemical
synthesis,plasmaprocessesaredrywithnoorlimiteduseofsolventsorpotentiallyharmfulchemical
substances, making them, in many cases, a highly valuable “green” alternative to “wet” chemical
methods. Enormous advancement in the use of plasma technologies was also enabled by recent
progressinplasmascienceandtechnology,especiallyinthecaseofatmosphericpressuredischarges,
aswellasbyclosecollaborationsofplasmaphysicistswithchemists,biologists,andmedicaldoctors.
Thisbroadenedtherangeofpossibleapplicationsofnon-equilibriumplasmasthatnowadaysinclude
sterilization/decontaminationofsurfaces[8–13],plasmamedicine[14–17],agriculture[18–22],orasit
willbediscussedinthisreview,theproductionofantibacterialcoatings[23–25].
In order to highlight the state-of-the-art plasma-based strategies for the deposition of
silver-containing antibacterial coatings, the article is organized as follows: In Section 2, different
approachesthatmaybeusedforthesuppressionofbacteriaadhesionorbiofilmsformationwillbe
brieflysummarized,withemphasisgiventoAg-containingnanocomposites. Differentplasma-based
strategiesthatweredevelopedfortheproductionofAg/plasmapolymernanocompositeswillbe
presentedinSection3.Finally,Section4willcoverthechallengesandfutureperspectivesoftheplasma
depositionofantibacterialcoatings.
Antibiotics2018,7,78;doi:10.3390/antibiotics7030078 www.mdpi.com/journal/antibiotics
Antibiotics2018,7,78 2of17
2. AntibacterialCoatings
Preventing the bacterial colonization of surfaces is a key requirement to limit the spread of
infections. Although this is important in various fields (e.g., the textile industry, food packaging
production,orspacemissions[26–30]),mostoftheattentionisdevotedtosurfacesusedinmedicine
andhealthcareservices. Here,thepresenceofbacteriaonmedicalinstruments,tools,accessoriesetc.
mayhavecatastrophicconsequences.Althoughmanyofthefactorsleadingtobacterialinfectioncanbe
easilyavoidedbyappropriatehygieneproceduresinthehospitals,itisimpossibletocompletelyavoid
bacterialinfections. Forexample,thisistrueinthecaseofmedicalimplants. Itiswellknownthat
planktonicbacteriapresentinbodyfluidsmayadheretotheimplantsurfaceinvivo,multiply,andstart
toformcomplexandhighlyresistantcommunities,suchasbiofilms,wherebacteriacansurvivefor
extendedperiodsoftime. Thebiofilmsmaythenactaspersistentreservoirsforpathogenswhichmay
triggerinfections. This,inturn,oftennecessitatesre-operationandreplacementoftheinfectedimplant
thatnotonlyincreasescosts,butrepresentsseriousrisk—especiallyforelderlypatients. Apromising
strategyforreducingtheoccurrenceofsuchundesirableeventsistoavoidtheinitialattachmentof
bacteriatotheimplant’ssurface. Generally,thiscanbedonebyfollowingtwostrategies[31].
Thefirstoneisbasedoncoatingimplantswithnon-foulingthinfilms,i.e. filmsthatarecapable
ofresistingproteinadsorptionorbacteriaadhesion. Thetypicalexamplesofsuchmaterialsarepoly
(ethyleneglycol)(PEG)derivativesorzwitterionicpolymers,thathaveprovedtobeabletoreduceor
inhibit bio-fouling [32–36]. However, it has to be stressed that in most of the invivo experiments,
surfacesledonlytothedelayofbiofilmformationandrestrictedlonger-termstabilityandperformance.
Furthermore,non-foulingcoatingsarepronetodamageduringtheirhandling.
The second way in which to combat biofilm formation is by the production of surfaces
that actively kill bacteria. This may be achieved either by contact-killing, or by release-based
strategies. The contact-killing of adhered bacteria is achieved either by antimicrobial compounds
covalentlyanchoringtothematerialsurface. Examplesincludequaternaryammoniumcompounds,
cationicpeptides,orenzymes[23,37,38],orthedesignofbiomimeticnanostructuredcoatingswith
high-aspect-ratiosurfacetopographiesthatexhibitbiocidalefficacy[39,40]. Inthecaseofrelease-based
coatings, antibacterial action is connected with the gradual leaching of antibacterial agents from
the coatings into the surrounding media. The antimicrobial agents may either be organic or
inorganic [23,31,41]. Regardless of the antibacterial agent used, its local delivery at a specific site
ensuresahighlocaldosewithoutexceedingthesystemictoxicity. Becauseofthis,varioustechniques
fortheproductionofsuchantibacterialcoatingsweredeveloped,includingplasma-basedonesthat
utilizedorganicantibiotics[42,43].
However,despitethesuccessoftheseapproaches,silver-basedmaterialshavebeenreceiving
increasingattentionsincethe1960s. Thiswascausedbyongoingreportsonthedevelopmentofthe
resistanceofcertainbacteriatocommonlyusedantibiotics(e.g.,[44–50]). Eventhoughthisisalsothe
caseforsilver,wherereportsexistwhichindicatetheoccurrenceofsilver-resistantbacteria[51,52],
thedevelopmentofbacterialresistancetowardsAgishighlyimprobableduetothemultiplepossible
pathwaysthatmayleadtobacterialdamagebysilvernanoparticles(NPs). Theexactmechanismofthe
antibacterialactionofAgNPsisstillnotfullyunderstood,andisafrequenttopicofdiscussionand
controversy. AgNPsmayeitherinducetheformationofreactiveoxygenspecies(ROS)ormayrelease
inaqueousmedia,suchashighlybioactivesilverions. TheROSandAg+ionsproducedsubsequently
interactwithDNAorthethiolgroupsofmoleculespresentinthecytoplasm,cellmembrane,andinner
membraneofmitochondria,thatmayresultinchangesinpermeability,disturbanceofrespiration,
leakageofintracellularcontent, inhibitionofproteinsynthesisandfunction, andcellapoptosisor
necrosis[52–55].
Naturally,thesilverNPsandreleasedsilverionsmayinteractnotonlywithbacteria,butalso
withtissuecells. Fortunately, thehealthrisksassociatedwithsystemicabsorptionofAg+ ionsare
ratherlow[56]. Nevertheless, inordertoavoidanyundesirableside-effectsconnectedwithsilver
Antibiotics2018,7,78 3of17
release, itsdosagehastobecarefullycontrolledandregulated, whichisoneofthekeychallenges
connectedwiththeapplicationofsilver-basedantibacterialnanocomposites.
3. AntibacterialAg/PlasmaPolymerNanocomposites
Numerousstudieshavebeendevotedtothefunctionalizationofsurfaces(mostlypolymericones)
byantibacterialnanosilver(e.g.,[57–62]). However, alimitationoftheproposedmethodswasthe
pooradAhnetisbiiootincs o20f18s,i 7lv, xe rtosubstrates,whichoftenledtothewashing-outofAgNPsfromt3h oef s17u bstrate,
which came with unacceptable pollution of the environment. Although it was demonstrated by
3. Antibacterial Ag/Plasma Polymer Nanocomposites
differentgroupsthatthiseffectmaybesubstantiallysuppressedbyplasmaactivation/functionalization
Numerous studies have been devoted to the functionalization of surfaces (mostly polymeric
ofsubstratematerialspriortothesilverdeposition(e.g.,[63–68]),inmanycasesthestabilityofAg
ones) by antibacterial nanosilver (e.g., [57–62]). However, a limitation of the proposed methods was
layersstillremainedquestionable. Becauseofthis,alternativestrategiesbasedontheembeddingof
the poor adhesion of silver to substrates, which often led to the washing-out of Ag NPs from the
AgNPssuinbsttoraates, uwpphiochrt incagmme awtriitxh wuenraeccseuptgagblees tepdol.luFtrioonm otfh ethsee peonivnirtosnomfevnite. wA,lpthloausgmha ipt owlyams ersare
considedreemdotonsbtreathedig hbyly dpifrfoemrenist ingrgoumpast rtihxatm thaitse reifaflesc,t i.me.aym baec rsoumbsotalenctiuallalyr ssuoplipdrsestsheadt bayre pclraesamtae dwhen
anorganacitcivvaatipoonu/frunocrtiporneacliuzarstioorn poaf sssuebsstthrartoeu mgahtearipallsa spmrioar[ 6to9 –th7e4 ]s.ilIvnerc odnetproassittitoon c(oe.ngv., e[n63ti–o6n8]a)l, pino lymers,
many cases the stability of Ag layers still remained questionable. Because of this, alternative strategies
plasmapolymershavearandomandirregularstructurewithhigherdegreesofcrosslinking,anda
based on the embedding of Ag NPs into a supporting matrix were suggested. From these points of
branchedstructure. Despitetheircomplexstructure,plasmapolymersoffercertainadvantages-they
view, plasma polymers are considered to be highly promising matrix materials, i.e. macromolecular
canbedsoelpidos stihteatd airne ctrheeatfeodr wmheonf cano nofrogramnica lv,appionu-rh oorl eprferceuerstohri npafisslems sthoronugahn ya spulabsmstar a[t6e9–m74a]t. eIrni alwith
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widerahniggeheor fdoepgreereast ioof ncarolscsolinnkdiintgio, nansd( ea. gb.r,aanpchpeldie dstrpuoctwureer., Dpersepciuter sthoeri/r wcoomrkplienxg sgtrausctmuriex, tpulraesm,par essure)
polymers offer certain advantages- they can be deposited in the form of conformal, pin-hole free thin
spanfromsofttohardpolymers,frombio-foulingtonon-fouling,orfromfilmsthatarestable,swelling,
films on any substrate material with well-controlled thicknesses at a nanometre scale. Furthermore,
ordissolvableinaqueousmedia. Theuseofplasmapolymersthusmaynotonlyimprovethefixation
their properties that can be tuned by a wide range of operational conditions (e.g., applied power,
onAgNPsandavoidtheirreleasetosurroundingmedia,but,duetothehighflexibilityofplasma
precursor/working gas mixture, pressure) span from soft to hard polymers, from bio-fouling to non-
polymefrosuilnintge, romr sfroomft hfilemirs pthhayt sairceo s-tcahbelem, siwcaelllainngd, obri od-iassdohlveasbilvee inp raoqpueeorutise ms,eadlisao. Ttahiel ourset hoef iprlaasnmtiab acterial
orbio-fpooullyimngerps ethrufos rmmaay nncoet .oInnlyt ihmepfroolvleo wthein fgixattwioon soun bAsge cNtiPosn asn,dd aivffoeidre tnhteiar prepleraosaec thoe ssurtrhoautnwdienrge tested,
withthemaeidmia,o bfupt, rdoudeu toc itnhge hAiggh/ fplelxaisbmilitay poof plylamsmera npoalnyomceorms inp otesrimtess o,fw thiellirb pehsyusimcom-chaermiziecadl. and bio-
adhesive properties, also tailor their antibacterial or bio-fouling performance. In the following two
3.1. LayseurebdseNctaionnosc, odmifpfeorseintet sapproaches that were tested, with the aim of producing Ag/plasma polymer
nanocomposites, will be summarized.
Sandwich or multi-layer structures (see Figure 1) represent the first family of antibacterial
Ag/pla3s.m1. aLapyeorleyd mNaenroncoamnpoosciotems posites. SuchcoatingstypicallyconsistofAgNPsovercoatedwitha
thintoplayeSarnodfwpilcahs mor ampuoltliy-lmayeerr (sttyrpucictuarlelys (fsreoem Fisgeuvree r1a)l nreapnreosmenett ethres tfoirstte nfasmoiflyn oafn oanmtiebtaecrtesr)iathl atfixes
AgNPsAogn/palassmubas ptroalytemmer antaenroiacolmanpdosaitcetss. Sauscah dcoifaftuinsgiso ntypbiacrarlliye rcofonsrislet aocf hAign gNAPsg o+vieorcnosa.teAdg wNithP sa maybe
thin top layer of plasma polymer (typically from several nanometers to tens of nanometers) that fixes
depositedonasubstrateeitherbyimmersionintoacolloidalsolutionofAgNPsfollowedbydrying,
Ag NPs on a substrate material and acts as a diffusion barrier for leaching Ag+ ions. Ag NPs may be
salt reduction, or physical methods, such as evaporation, magnetron sputtering, or the use of gas
deposited on a substrate either by immersion into a colloidal solution of Ag NPs followed by drying,
aggregationsources(GAS)ofsilverNPs(seeFigure2). ThephysicalmethodsofAgNPsdeposition
salt reduction, or physical methods, such as evaporation, magnetron sputtering, or the use of gas
arehighalgygraedgavtaionnt asoguerocuess ,(GaAsSth) eoyf sliilvmerit NthPse (pseoes Fsiigbulereu 2n).c Tohnet rpohlylseidcaal gmgertheogdast ioofn Aogf NAPgs dNepPossoitnions urfaces,
ensureahrieg hhigphulyr iatdyvoanftsaiglevoeurs,N asP tsh,eayn lidmmit tahye pboesseiablsei luynccoonmtrbolilnede dagwgrietghatoiothn eorf Alogw N-Ppsr eosns suurrefadceesp, osition
techniqeunessuures ehdighfo prupriltays omf asilpvoerl yNmPes,r amnda tmriaxy dbeep eoassiiltyio cnom. Ibninoerdd werittho oftahceirl iltoawte-ptrhesesuardeh deespioosnitioofnA gNPs
techniques used for plasma polymer matrix deposition. In order to facilitate the adhesion of Ag NPs
ontoasubstrateadditionalbottomlayer(oftenplasmapolymerfilm)isusedasaninterfacebetween
onto a substrate additional bottom layer (often plasma polymer film) is used as an interface between
thesubstrateandAgNPs.
the substrate and Ag NPs.

Figure 1. Common structure of (a) sandwich and (b) multi-layered Ag-based nanocomposites.
Figure1.Commonstructureof(a)sandwichand(b)multi-layeredAg-basednanocomposites.
Antibiotics2018,7,78 4of17
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antibacterial Ag+ responsible for antibacterial action of produced coatings was found to be strongly
linked with the number of silver NPs in the coatings, as well as with the thickness of the top barrier
Antibiotics2018,7,78 5of17
aAcnttiiboinoticosf 2p01r8o, d7,u xc edcoatingswasfoundtobestronglylinkedwiththenumberofsilverNPsi5n otf h1e7
coatings,aswellaswiththethicknessofthetopbarrierlayer. Thisallowsforthefabricationofthe
claoyaetirn. gTshwis iathlloewiths efrora tbhuer fsat-brreilceaatsioeno fosf itlhvee rcoioantisn,gosr wasitlho weitbhuetr tae mbuprosrta-rlleylesatsaeb loef lseialvcehri niognosf, Aorg a+ siloonws.
but temporally stable leaching of Ag+ ions.
Although the low-pressure deposition systems were traditionally used for the production of
Although the low-pressure deposition systems were traditionally used for the production of
plasmapolymerovercoats,thepossibilitytoalsouseatmosphericpressuredepositionsystemswas
plasma polymer overcoats, the possibility to also use atmospheric pressure deposition systems was
suggestedbyDengetal.[101,102]. Theseauthorsusedanatmosphericpressureplasmajetoperated
suggested by Deng et al. [101,102]. These authors used an atmospheric pressure plasma jet operated
inamixtureofN /O /tetramethyldisiloxane(TMDSO)toproduceabarrierlayerdepositedontopof
2 2
PinE Ta mfaibxrtiucrsec ooaf tNed2/Ow2i/tthetAragmNethPysl.dIitsiwloxaasndee (mTMonDstSrOat)e dtot hparotdthuecea nat ibbaarcrtieerr ialalyeefrfe dctepoofssiutecdh ponre tpoapr eodf
PET fabrics coated with Ag NPs. It was demonstrated that the antibacterial effect of such prepared
fabrics on P. aeruginosa, S. aureus, C. albicans and E. coli may be varied by the thickness of the top
fabrics on P. aeruginosa, S. aureus, C. albicans and E. coli may be varied by the thickness of the top layer.
layer. Furthermore,thetoplayerwasconfirmedtoenhancethestabilityofantibacterialeffect,andno
Furthermore, the top layer was confirmed to enhance the stability of antibacterial effect, and no
variationofantibacterialactionwasobservedafter10washingcycles[101].
variation of antibacterial action was observed after 10 washing cycles [101].

FFiigguurree 33.. SSchcheemmaatitci crerperperseesnetnattaiotino nofo pfopssoisbslieb plelapslmasam-baa-sbeads estdrasttergaiteesg fieosr tfhoer othveerocovaetricnoga toifn Aggo Nf APsg.
N(aP) sP.l(aas)mPala-semnhaa-nencehda nccheedmcihceaml ivcaaplovra pdoerpdoespitoiosnit io(PnE(-PCEV-CDV).D I)n. Itnhtihs ismmetehtohdo,d ,oorgrgaannicic vvaappoouurrss oorr
pprreeccuurrssoorrss aarree iinnttrroodduucceedd iinnttoo tthhee ppllaassmmaa,, wwhheerree tthheeyy aarree aaccttiivvaatteedd aanndd ffrraaggmmeenntteedd.. FFoorrmmeedd rraaddiiccaallss
tthhaatt ccoonnddeennsseeo onna as usbusbtrsatrtaetseu sbusebqseuqeunetlnytluyn duenrdgeorgfroe efrreaed ircaadlicchaal inchgarionw gtrhopwotlhy mpoerlyizmateiroinza(ftoiornm (oforer
dmeotareil sd,eptlaeialsse, prelefearseto rtehfeerm too ntohger ampohnieosg[r6a9p,7h1ie,7s2 ][6o9r,7r1ev,7i2e]w osr[ 2r,e2v4i,e7w4]s) .[(2b,2)4R,7F4m]).a g(bn)e tRroFn mspaugtnteertrinogn
ospfuatpteorliynmg eorfi ca tpaorglyemt.eInrict htaisrgcaest.e I,ns ttahritsi ncgasme,a sttearritailnigs msuaptperliiaedl isin suthpepfloierdm ino fthaes ofolirdm-s toaft ea psoolliydm-setaritce
tpaorlgyemttehraict itsaargtteatc htheadt oins toatatamchaegdn eotnroton .aA mtoamgsn,emtroolne.c uAlteosm,asn, dmmoolelceuculelsa,r afrnadg mmeonltescusplaurt tferraegdmfreonmts
tshpeupttoelryemd efrroicmta trhgee tpcoolynmseeqruice ntatlrygepta crotincispeaqtueeinntlpyl apsamrtaicpipoalytem ienr ipslaatsiomna, apsoilnymtheeriPsEat-iCoVnD, a.sI ninc tohnet rPaEst-
tCoVsDpu. tItner icnogntorfamste ttoa llsipcutatrtegreitnsg,p oofl ymmeetrasllaicre tnarogtectosn, dpuocltyimvee,rms eaarnei nngott hcaotnRdFupctoiwvee,r mhaesantoinbge athpaptl iRedF.
Mpoawgnere throans tsop ubtet earpinpgliewda. sMemagpnleotyreodn fsopruthtteerpinrogd wucatsio enmopflaoyweidd eforra nthgee pofropdlauscmtiaonp oolfy am werisd,ein rcalnugdein ogf
Cpl:aHs,mCa: Hp:oNly:Om,eorrs,C i:nFcolundeisn(ge .Cg.:,H[1, 0C3:–H1:0N9]:O).,( co)rA Ctm:F oosnpehse r(eic.gp.,r e[s1s0u3r–e10p9la])s.m (ca) jAettsm.Tohspesheersiycs tpermesssuarree
bpalasesmdoa njePtsE.- CThVeDsep sryoscteesms,sb uatret hbeagseadse oouns PoEr-lCiqVuDid pprroecceusrss,o brsuta rtehein gtraosdeuocuesd otro ltihqeuipdl apsrmeacuigrsnoirtesd aaret
aintmtroodspuhceerdic tpo rtehsesu prela.sDmifaf eirgennittecdon afitg autrmatoiospnhseorfica tpmroesspsuhreer.i cDpirfefesrseunret pcolansfmigaujreattsiownesr eofd eamtmoonssptrhaetreidc
tporebsesusureit apblalesmfoar jtehtes dweeproes diteiomnoonfstvraartieodu tsop blaes smuaitapbolley mfoer rthfielm dsep(eo.gsi.t,i[o1n1 0o–f 1v1a8r]i)o.us plasma polymer
films (e.g., [110–118]).
3.2. DirectEmbedmentofAgNPsintoPlasmaPolymerMatrix
3.2. Direct Embedment of Ag NPs into Plasma Polymer Matrix
As shown in the previous section, layered silver-containing structures are highly effective at
killinAgsb sahcotewrina .in Hthoew perveevri,otuhse sdecetpioonsi,t iloaynerperdo cseidlvuerre-cionnvtoailnviensgm sturluticptuleresst eapres, hwighhilcyh eifsf,ecftriovme aat
tkeicllhinngo lobgaicctaelripao. iHntoowfevvieerw, ,thael imdeitpionsgitfiaocnt opr.roCceodnuserqe uiennvtolylv,easl temrnualttiipvlee asptpeprosa, cwhehsicfho risA, gf-rboamse da
nteacnhoncoolmogpicoasli tpeopinrot douf cvtiioewn,w ae rliemdietivnegl ofpacetdo,r.i nCwonhsiecqhuAengtlnya, naoltpearnrtaitcilvees aapreprinocaochrpeso rfaotre dAgd-ibreacsteldy
innatnootchoemgprooswitein pgropdlauscmtioanp woelyrem deervmelaotpreixd., inO wnehiocfh tAhge nfiarnstopaattretmiclpetss artoe winacrodrptohrisateddir decirtieocntlyw inertoe
rthepe ogrrtoewdibnyg Fpalavsimaae tpaoll.y[m11e9r] manadtriSxa. rOdneell aofe tthael .fi[r1s2t 0a]t.teTmhpetsse taouwtharodr sthpirse dpiarreecdtiocno nwfoerrem raelpcooratetdin bgys
wFaitvhias eiltv aelr. [N11P9s] aenmdb Seadrddeedllain eta alp. o[l1y2e0th].y Tlehneeseo xaiudeth-loikrse p(PreEpOar-leidk ec)omnfaotrrmixa,l ucosiantgingPsE w-CiVthD silfvroemr NRPFs
gemlowbedddisecdh ainrg ae spofelydetwhyitlhenAe ro,xaidned-ldikieet h(PylEgOly-cloikl-ed)i mmeathtryilx-e, tuhseirn(gD PEEG-MCVED)w friothms iRmFu gltloanwe oduisscshpaurgtteesr ifnedg
fwroitmh tAhre, AangdR Fdieetlheycltgrolydceoli-ndimanetahsyyl-metmheer tr(DicEpGaMraEll)e lw-piltaht esicmonufiltgaunreaotuiosn s(psueteteFriignugr efr4oam). tDhue eAtog tRhFe
reeleaccttroordaes iynm amn aestryym,nmeegtaritciv peaDraCllesle-plfl-abtiea csodnefvigeulorapteidono (nseteh Feisgmurael l4ear)A. Dgueel etoct trhoed ree,awcthoirc ahsylemdmtoettrhye,
bnoemgabtiavred mDeCn steolff-tbhieasA dgetvaerlgoeptebdy ohnig thhley semnearlgleert iAcgio enlsecintrdoudcei,n wghsiilcvhe rlesdp utott ethrien bgo.mEmbaitrtdedmAengt aotfo tmhes
Ag target by highly energetic ions inducing silver sputtering. Emitted Ag atoms impinged upon the
plasma polymer surface, which grew simultaneously by plasma polymerization. Ag atoms, due to
their limited diffusion in a cross-linked matrix, subsequently formed stable metal nanoparticles
through an aggregation process. The properties of the resulting nanocomposites (Ag filling factor,
Antibiotics2018,7,78 6of17
impingedupontheplasmapolymersurface,whichgrewsimultaneouslybyplasmapolymerization.
Agatoms,duetotheirlimiteddiffusioninacross-linkedmatrix,subsequentlyformedstablemetal
Antibiotics 2018, 7, x 6 of 17
nanoparticlesthroughanaggregationprocess. Thepropertiesoftheresultingnanocomposites(Ag
fillingfactor,sizeofAgNPs,andPEO-likecharacterofthematrix)werecontrolledbyoperational
size of Ag NPs, and PEO-like character of the matrix) were controlled by operational parameters
parameters (power, pressure, and Ar flow). Based on the disk diffusion test that was performed
(power, pressure, and Ar flow). Based on the disk diffusion test that was performed with S.
with S. epidermidis, it was reported that the inhibition area correlated with the Ag content in the
epidermidis, it was reported that the inhibition area correlated with the Ag content in the coatings.
coatings. SimilarapproachesusingsimultaneousplasmapolymerizationandAgsputteringwassince
Similar approaches using simultaneous plasma polymerization and Ag sputtering was since then
thenemployedbyotherresearchgroups,whichutilizeddifferentprecursors/workinggasmixtures.
employed by other research groups, which utilized different precursors/working gas mixtures.
PreparednanocompositesweretestedtowardsbothGramm-negativeandGramm-positivebacteria
Prepared nanocomposites were tested towards both Gramm-negative and Gramm-positive bacteria
(for a summary of results, please refer to Table 1). Furthermore, it was found that Ag/HMDSO
(for a summary of results, please refer to Table 1). Furthermore, it was found that Ag/HMDSO
nanocompositeswithproperly-tunedsilvercontentmaynotonlykillbacteria,butalsodrastically
nanocomposites with properly-tuned silver content may not only kill bacteria, but also drastically
reducemicrobialadhesion[121,122].
reduce microbial adhesion [121,122].

Figure 4. Different approaches for the production of Ag/plasma polymer nanocomposites: (a)
Figure 4. Different approaches for the production of Ag/plasma polymer nanocomposites:
Simultaneous sputtering and plasma polymerization, (b) deposition from two independent magnetrons,
(a) Simultaneous sputtering and plasma polymerization, (b) deposition from two independent
and (c) a combination of a gas aggregation source and plasma polymerization.
magnetrons,and(c)acombinationofagasaggregationsourceandplasmapolymerization.
The great advantage of simultaneous sputtering and plasma polymerization is that it is a single-
The great advantage of simultaneous sputtering and plasma polymerization is that it is a
step process. However, as the sputtering and plasma polymerization are fully coupled, it is not
single-stepprocess. However,asthesputteringandplasmapolymerizationarefullycoupled,itis
possible to independently tailor the size of Ag NPs and their amount in the films and matrix
not possible to independently tailor the size of Ag NPs and their amount in the films and matrix
properties. In order to overcome this limitation, another procedure that is based on co-sputtering
properties. In order to overcome this limitation, another procedure that is based on co-sputtering
from two independent magnetron sources may be used (see Figure 4b). The volume fraction of silver
fromtwoindependentmagnetronsourcesmaybeused(seeFigure4b). Thevolumefractionofsilver
in a matrix material is, in this case, controlled by the power applied to the individual magnetrons.
inamatrixmaterialis,inthiscase,controlledbythepowerappliedtotheindividualmagnetrons.
This approach, which is also applicable for the production of inorganic Ag containing antibacterial
Thisapproach,whichisalsoapplicablefortheproductionofinorganicAgcontainingantibacterial
nanocomposites (e.g., Ag/silica [123], Ag/hydroxyapatite [124], or Ag/TiO2 [125]), was used for the
nanocomposites (e.g., Ag/silica [123], Ag/hydroxyapatite [124], or Ag/TiO [125]), was used for
fabrication of Ag/C:F antibacterial films by Zaporojtchenko et al. [126]. It 2was reported that the
thefabricationofAg/C:FantibacterialfilmsbyZaporojtchenkoetal.[126]. Itwasreportedthatthe
nanocomposites produced steadily supplied silver ions for a long period of time (reported values
nanocomposites produced steadily supplied silver ions for a long period of time (reported values
were for 300 days) and exhibited antibacterial effects towards S. epidermidis, S. aureus, and P.
werefor300days)andexhibitedantibacterialeffectstowardsS.epidermidis,S.aureus,andP.aeruginosa.
aeruginosa. Moreover, an addition of a small amount of Au (1%) was found to substantially increase
Moreover,anadditionofasmallamountofAu(1%)wasfoundtosubstantiallyincreasetherelease
the release rate of silver ions (by one order of magnitude) [126]. This effect is explained by the
rate of silver ions (by one order of magnitude) [126]. This effect is explained by the formation of
formation of galvanically-coupled Ag and Au NPs, because in the galvanic pair, silver is more active
than gold, and the presence of gold enhances Ag+ ion formation.
Antibiotics2018,7,78 7of17
galvanically-coupledAgandAuNPs,becauseinthegalvanicpair,silverismoreactivethangold,
andthepresenceofgoldenhancesAg+ionformation.
Table1.OverviewofthereportedantibacterialeffectofAg/plasmapolymernanocomposites.
WorkingGas
DepositionMethod Precursor Bacteria Result Reference
Target
Simultaneoussputtering Agtarget
StaphylococcusEpidermidis Inhibitionzone6mm [120]
andplasmapolymerization Ar/DEGME
Simultaneoussputtering Agtarget Pseudomonasaeruginosa,
Bacterialgrowthdownto0% [127]
andplasmapolymerization Ar/NH3/C2H4 Staphylococcusaureus
Agtarget
Simultaneoussputtering Pseudomonasaeruginosa,
andplasmapolymerization Ar/NH3/C2H4 Staphylococcusaureus >7logreduction [128]
Ar/CO2/C2H4
Simultaneoussputtering Agtarget Escherichiacoli, E.Coli>6logreduction
[129]
andplasmapolymerization Ar/HMDSO Staphylococcusaureus S.aureus>1log
Simultaneoussputtering Agtarget
Saccharomycescerevisiae 1.9logreduction [130]
andplasmapolymerization Ar/HMDSO
MRSA,
MRSE,VRE, Inhibitionzone20–22mmforall
Simultaneoussputtering Agtarget Escherichiacoli testedbacteria.
[131]
andplasmapolymerization polyaniline Pseudomonasaeruginosa, >6logreductionforE.Coliand
Proteusmirabilis, MRSA
Klebsiellapneumoniae
Simultaneoussputtering Agtarget
Staphylococcusaureus 99%ofbacteriakilled [132]
andplasmapolymerization C2H2
Staphylococcusepidermidis,
Staphylococcusaureus,
Enterococcusfaecalis,
AgandPTFE
Co-sputtering Pseudomonasaeruginosa, 7logreductionforS.aureus [126]
targets
Escherichiacoli,
Klebsiellapneumoniae,
Candidaalbicans
GASsystemcombinedwith AgGAS
Escherichiacoli Almost3logreduction [133]
plasmapolymerization Ar/n-hexane
AnotherstrategythatmakesitpossibletocompletelydecouplethedepositionofAgNPsandthe
plasmapolymermatrixisbasedontheuseofgasaggregationsources[134,135]. Thisapproachwas
recentlyusedbyVaidulychetal.[133]forthedepositionofAg/a-C:Hnanocomposites. Inorderto
producehardcoatings,thesubstrateswereplacedonaRFelectrode,usedfora-C:Hmatrixdeposition,
perpendicularlytothedirectionofabeamofAgNPsproducedbytheGASsystem(Figure4c). Asit
was shown in a previous study focusing on Cu/a-C:H nanocomposites [136], the volume fraction
ofmetallicNPsina-C:Hmatrixandconnectedantibacterialefficiencymaybetunedeitherbythe
current applied onto the DC magnetron in the gas aggregation source, or by changing the duty
cycle of RF power used for the matrix deposition. Furthermore, it was reported that antibacterial
actionofAg/a-C:Hcoatingsmaybeenhancedbythepartialetchingofnanocompositesbyplasma
treatmentperformedinthesamedepositionchamberresultinginpartialremovalofacarbonaceous
layerfromtheoutermostsurfaceofproducednanocomposites,thusmakingAgNPsmoreaccessible
forwater[133].
Acompletelydifferentone-stepprocessapplicableforthedepositionofAg/plasmapolymer
antibacterialfilmswasproposedbyZimmermanetal.[137],Beieretal.[138],andGerullisetal.[139].
Theseauthorsusedanatmosphericpressureplasmachemicalvapordepositiontechnique,inwhicha
HMDSOprecursorwasintroducedintotheatmosphericpressureplasma,togetherwithsilvernitrate
byamodifiedjetnozzle(Figure5a). Astrongantibacterialeffectofnanocompositesproducedinthis
wayonE.coliwasshownevenafter10,000washingcycles[138]. Atmosphericpressuredepositionwas
finallyalsotestedbyDengetal.[140],wheretheydirectlyintroducedAgNPs(100nmsize)instead
ofsilvernitrateintothefeedgas(N withadmixingofO andTMDSO)(Figure5b). Accordingto
2 2
thereportedresults,preparedcoatingsexhibitedstrongantibacterialeffectsagainstGramm-negative
Antibiotics 2018, 7, x 8 of 17
Antibiotics2018,7,78 8of17
nm size) instead of silver nitrate into the feed gas (N2 with admixing of O2 and TMDSO) (Figure 5b).
Antibiotics 2018, 7, x 8 of 17
According to the reported results, prepared coatings exhibited strong antibacterial effects against
Gramm-negative E. coli, and a modest effect on Gram-positive S. aureus. A similar approach was
E.colin,man sdizea) minostdeeasdt oeff fseilcvteor nniGtraratem in-ptoo tshitei vfeeedS .gaausr (eNu2s .wAiths iamdimlaixrianpg porfo Oa2c hanwd aTsMrDecSeOn)t l(yFiegmurpe l5oby)e. dby
recently employed by Ligouri et al. [141] for the production of plasma-polymerized polyacrylic acid
LigouArciceotradli.n[g1 4to1 ]thfoer rtehpeorpterodd ruescutilotsn, porfepplaarsemd ac-opaotilnygms eerxihziebditepdo lsytarcornygl icanatciibdacwteirthiale meffbeectdsd aegdaiAnsgt NPs.
with embedded Ag NPs. Disk diffusion tests with E. coli confirmed the antibacterial efficacy of
DiskGdirfafmusmio-nnetgeasttisvew Eit. hcoEli., caonlidc ao nmfiordmeestd etfhfeecta nonti bGarcatmer-ipaolseitfifivcea Scy. aoufrefuasb. rAic astiemdilcaor aatpinprgosa.ch was
fabricated coatings.
recently employed by Ligouri et al. [141] for the production of plasma-polymerized polyacrylic acid
with embedded Ag NPs. Disk diffusion tests with E. coli confirmed the antibacterial efficacy of
fabricated coatings.

Figure 5. Schematic representation of atmospheric pressure plasma systems for the deposition of
Figure 5. Schematic representation ofatmospheric pressureplasma systemsfor the depositionof
Ag/plasma polymer nanocomposites. (a) Plasma jet with injection of silver nitrate solution, and (b)
Ag/plasmapolymernanocomposites.(a)Plasmajetwithinjectionofsilvernitrate solution,and(b)
plasma jet fed with suspension of Ag NPs.
plasmFaigjuetref e5d. Swchitehmsautsicp erenpsrieosnenotfatAiogn NofP sa.tmospheric pressure plasma systems for the deposition of
Ag/plasma polymer nanocomposites. (a) Plasma jet with injection of silver nitrate solution, and (b)
4. Perspectives and Challenges
4. Perspecptliavsmesa ajent fdedC whiathl lseunspgeenssion of Ag NPs.
Plasma-based techniques have been shown to present itself as an interesting option for the
Pp4r.l aoPdsemurscapti-eobcnat iosvefe dasn attniebdcah cCntheirqailaullee Ansgghe-bsa avseedb ceoeantinsghso. wInn adtdoitpiorne,s pelnatsmitas-eblafsaeds daenpoinsitteiorens tteicnhgnoolpogtiioesn afroe r the
produwcetlilo-snuiotefda nfotrib thace tperroiadluActgio-nb aosf endovceola atnintigbsa.ctIenriaadl cdoiatitoinng,sp wlaitshm ean-hbaansceedd dfuenpcotisointiaolintyt.e Tchhins orelofegrise sare
Plasma-based techniques have been shown to present itself as an interesting option for the
not only to the possibility to produce coatings with a multi-approach character that may combine the
well-spuroitdeudcftioornt ohfe apntriobdacutcetriioaln Aogf-bnaosveedl caonattiinbgasc.t eInr iaadldciotiaotnin, pglsaswmitah-beansehda ndcepedosfiutionnc ttieocnhanloitloy.giTehs iasrer efers
antibacterial action of Ag NPs with the non-fouling nature of a polymeric matrix (e.g., PEO-like
notownleyll-tsouitthede fpoor sthsieb pilriotydutcotiopnro odf unocveecl oaanttiibnagcstewriaitl hcoaatminugsl twi-iathp penrohaanchcedch fuarnacctitoenratlhitya.t Tmhiasy recfoerms bine
plasma polymers, Figure 6a), silver/plasma polymer nanocomposites with covalently immobilized
theanntoitb oancltye rtoia tlhaec ptioosnsiboiflitAy gtoN pProsdwucieth cothateinngos nw-iftohu al imngulnti-aatpuprreooafcha cphoarlyacmteerr tihcamt mataryi xco(me.bgi.n,eP tEhOe -like
bactericidal substances (Figure 6b), or surface nanotopography (Figure 6c), but also coatings with (i)
plasmanatpiboalcytemriearl sa,cFtiiognu roef 6Aag) ,NsiPlvs ewr/itph lathsem naopno-floyumlinegr nnaatnuorceo omf pa opsoitlyemsweriitch mcaotvriaxl e(ne.tgl.y, PimEOm-loikbeil ized
a temporally non-monotonous release of silver ions, (ii) so-called multi-release coatings that employ
bacteprilcaisdmaal spuoblysmtaenrcse, sFi(gFuigreu r6ea)6, bs)i,lvoerr/spularfsamcae pnoalnyomtoerp onganraopcohmyp(oFsigituesr ew6icth), cbouvtalaelnsotlyc oimatminogbsilwizeitdh (i)a
two or more antibacterial agents, or even (iii) thin films with Ag+ release induced by an external
bactericidal substances (Figure 6b), or surface nanotopography (Figure 6c), but also coatings with (i)
tempsotrimalulyli,n io.en.,- mcooatninogtos nthoauts wreerlee assuegogefsstieldv etro ifoancisli,t(aitie) spore-cvaelnletidonm ouf lbtai-crteelreiaals eincfeocattioinngss (eth.ga.,t [e3m1])p. lo ytwo
a temporally non-monotonous release of silver ions, (ii) so-called multi-release coatings that employ
ormoreantibacterialagents,oreven(iii)thinfilmswithAg+releaseinducedbyanexternalstimuli,
two or more antibacterial agents, or even (iii) thin films with Ag+ release induced by an external
i.e.,coatingsthatweresuggestedtofacilitatepreventionofbacterialinfections(e.g.,[31]).
stimuli, i.e., coatings that were suggested to facilitate prevention of bacterial infections (e.g., [31]).

Figure6.Ag-basedmulti-functionalcoatingswith(a)non-foulingcharacter,(b)Ag/plasmapolymer
nanocompositeswithcovalentlyimmobilizedantibacterialagents, or(c)ananostructuredplasma
polymertoplayer.
Antibiotics 2018, 7, x 9 of 17
Antibiotics 2018, 7, x 9 of 17
Figure 6. Ag-based multi-functional coatings with (a) non-fouling character, (b) Ag/plasma polymer
Antibiontiacnso20c1o8m,7p,o7s8ites with covalently immobilized antibacterial agents, or (c) a nanostructured plasma9 of17
Figure 6. Ag-based multi-functional coatings with (a) non-fouling character, (b) Ag/plasma polymer
polymer top layer.
nanocomposites with covalently immobilized antibacterial agents, or (c) a nanostructured plasma
poRlyemgearr dtoipn glacyoear.t i ngswithnon-monotonouskineticsinthereleaseofsilverions,twoapproaches
Regarding coatings with non-monotonous kinetics in the release of silver ions, two approaches
areunderinvestigation. ThefirstoneisbasedonthepossibilitytotuneAg+releasebythethicknessof
are under investigation. The first one is based on the possibility to tune Ag+ release by the thickness
Regarding coatings with non-monotonous kinetics in the release of silver ions, two approaches
thebarriertoplayer(Figure7). Inthiscase,differentpartsofAgNPscontainingfilmsmaybecoated
of the barrier top layer (Figure 7). In this case, different parts of Ag NPs containing films may be
are under investigation. The first one is based on the possibility to tune Ag+ release by the thickness
by plasma polymer films with different thicknesses. Zones with thin top layers will ensure burst
coated by plasma polymer films with different thicknesses. Zones with thin top layers will ensure
of the barrier top layer (Figure 7). In this case, different parts of Ag NPs containing films may be
release,whereaszonescoatedwiththickerfilmswillbecharacterizedbythedelayedandprolonged
burst release, whereas zones coated with thicker films will be characterized by the delayed and
colaetaecdh ibnyg polfaasmsma aplloelryammeoru fniltmosf Awgit+h. Tdhifefesraemnte tihsiecxkpneecstseeds.t oZboeneasc hwieivthe dthbiyn tthoeps leacyoenrds awpipllr oeancshurthe at
prolonged leaching of a smaller amount of Ag+. The same is expected to be achieved by the second
burst release, whereas zones coated with thicker films will be characterized by the delayed and
isbasedonmulti-layercoatings,orthecoatingswithadepthgradientinthenumberofembedded
approach that is based on multi-layer coatings, or the coatings with a depth gradient in the number
prolonged leaching of a smaller amount of Ag+. The same is expected to be achieved by the second
NPs. Suchmaterialsshouldfulfilltherequirementoflong-lasting(severalmonthsof)antibacterial
of embedded NPs. Such materials should fulfill the requirement of long-lasting (several months of)
approach that is based on multi-layer coatings, or the coatings with a depth gradient in the number
actionneededtopreventinfectionsonimplants.
antibacterial action needed to prevent infections on implants.
of embedded NPs. Such materials should fulfill the requirement of long-lasting (several months of)
antibacterial action needed to prevent infections on implants.

FFiigguurree 77.. SScchheemmee ooff AAgg//ppllaassmmaa ppoollyymmeerr ccooaattiinngg wwiitthh nnoonn--mmoonnoottoonnoouuss kkiinneettiiccss ooff rreelleeaa ssee ooff ssiillvveerr iioonnss..
Figure 7. Scheme of Ag/plasma polymer coating with non-monotonous kinetics of release of silver ions.
In the case of multi-release coatings, different antibacterial agents (e.g., silver and copper NPs
Inthecaseofmulti-releasecoatings,differentantibacterialagents(e.g.,silverandcopperNPsor
or Ag NPs and antibiotics) with different release kinetics and/or bactericidal effects can be combined.
In the case of multi-release coatings, different antibacterial agents (e.g., silver and copper NPs
AgNPsandantibiotics)withdifferentreleasekineticsand/orbactericidaleffectscanbecombined.
Such coatings should significantly reduce the induction of bacterial resistance and guarantee synergic
or Ag NPs and antibiotics) with different release kinetics and/or bactericidal effects can be combined.
Suchcoatingsshouldsignificantlyreducetheinductionofbacterialresistanceandguaranteesynergic
antibacterial action, thus enhancing antibacterial efficiency. Possible structures under consideration
Such coatings should significantly reduce the induction of bacterial resistance and guarantee synergic
antibacterialaction,thusenhancingantibacterialefficiency. Possiblestructuresunderconsideration
include silver-containing plasma polymer films impregnated with antibiotics (Figure 8a),
antibacterial action, thus enhancing antibacterial efficiency. Possible structures under consideration
includesilver-containingplasmapolymerfilmsimpregnatedwithantibiotics(Figure8a),sandwiched
sandwiched structures with different metallic NPs with antibacterial character (Figure 8b), or multi-
include silver-containing plasma polymer films impregnated with antibiotics (Figure 8a),
structureswithdifferentmetallicNPswithantibacterialcharacter(Figure8b),ormulti-layeredcoatings
layered coatings prepared by a step-by-step deposition, in which individual layers will be loaded
sandwiched structures with different metallic NPs with antibacterial character (Figure 8b), or multi-
prepared by a step-by-step deposition, in which individual layers will be loaded with different
with different antibacterial agents (Figure 8c).
layered coatings prepared by a step-by-step deposition, in which individual layers will be loaded
antibacterialagents(Figure8c).
with different antibacterial agents (Figure 8c).
Figure 8. Different architectures suggested for multi-release coatings.
Figure 8. Different architectures suggested for multi-release coatings.
Plasma-based deposition techniques may also be utilized for producing coatings with stimuli-
Figure8.Differentarchitecturessuggestedformulti-releasecoatings.
responsive behavior. These materials benefit from the ability of some materials to undergo volume
Plasma-based deposition techniques may also be utilized for producing coatings with stimuli-
or structural changes when exposed to a particular trigger. This property may be utilized for
responPsilvaes mbeah-baavsioedr. Tdheepsoes mitiaotneritaelcs hbneinqeufeits frmomay thael saobilbitey uoft isliozmede mfoartepriraolsd utoc iunngdecrogaoti nvoglsumweit h
controlling the release of antibacterial agents, including silver ions, from the coatings “on demand”.
ors tsitmruucltiu-rreaslp cohnasnivgeesb ewhhavenio re.xTphoesseed mtoa tear ipalasrtbiceunleafirt tfrriogmgetrh. eTahbisil iptyroopfesrotmy emmaya tebrei aulstitloizuedn dfeorrg o
The first example of Ag/plasma polymer nanocomposites with this ability was reported by Kulaga et
covnotrluolmlinego rthsetr rueclteuarsael ocfh aanngtiebsacwtehreinal eaxgpeonstesd, itnoclaupdainrtgic suillvarert riiogngse,r f.rTohmis thpero cpoearttiyngms a“yonbe duetmiliaznedd”f. or
al. [142]. These authors coated polypropylene surgical mesh with a layer of plasma-polymerized
Thceo nfitrrsot lelixnagmtphlee roefl eAagse/polfasamntaib paocltyemriaelr angaennotcso,minpclousditiensg wsiiltvhe trhiios nasb,ilfirtoym wtahse rceopaotritnegds b“yo nKudleamgaa netd ”.
maleic anhydride (MA), impregnated with silver NPs and coated by a barrier layer (plasma
al.T [h1e42fi]r.s tTehxeasme apulethoofrAs gc/oaptleadsm paolpyoplryompeyrlennaen soucorgmicpaol smiteesshw withithth ais laabyielirt yofw palsarsempao-rpteodlybmyeKriuzeladg a
polymerized MA) that blocked the spontaneous release of silver from the coatings. Tailored release
maelteiacl .a[1n4h2y]d.rTidhee s(eMaAu)t,h oimrspcroeagtnedatepdo lywpirtohp ysillevneer suNrPgsic aalnmd eschoawteidth abyla yae rboafrrpielars mlaay-epro l(ypmlaesrmizae d
of silver ions was then achieved by mechanical stimulation of the coatings that led to the formation
pomlyamleiecraiznehdyd MridAe)( MthAat) ,bilmocpkreedg ntahtee dspwointhtasnielvoeursN rePlseaasned ocfo saitlevderb yfroamba trhriee rcolaaytienrg(sp.l aTsamiloarpeodl yrmeleeariszee d
of cracks in the barrier layer. Moreover, plasma polymerization may also be used for the production
ofM siAlv)erth iaotnbs lwocakse tdhethne ascphoienvteadn eboyu msreeclheaasneicoafl ssitlivmeurlfartoimont hofe tchoea ctionagtsin.gTsa itlhoaret dlerde lteoa tsheeo ffosrimlvaetrioionn s
of other types of stimuli-responsive plasma polymers where changes in the temperature or pH acts
ofw craasckthse inn athche ibeavrerdiebr ylamyeerc. hManoriceaolvsetri,m pulalasmtioan pooflytmheerciozaattiinogns mthaayt alelsdo tboe tuhseefdo rfomra tthioe nproofdcuracctikosni n
as a trigger. For instance, Pan et al. [143], Spridon et al. [144], Chen et al. [145], and Moreno-Couranjou
oft ohtehbera rtryipeersl aoyf esrt.imMuolir-eroevspero,npsliavsem palapsmolay mpoelryizmaetirosn wmhearye aclhsoanbgeesu isne dthfeo rtetmhepeprraotduurec toior npHof aoctths er
ast ay ptreisggoefrs.t Fimoru ilni-srteasnpcoen, sPivaen petl aaslm. [a14p3o],l ySmpreirdsown heet rael.c [h1a4n4g],e Cshinenth eet atel.m [1p4e5r]a,t aunred oMroprHenaoc-tCsoasuraatnrjiogug er.
Antibiotics2018,7,78 10of17
Forinstance,Panetal.[143],Spridonetal.[144],Chenetal.[145],andMoreno-Couranjouetal.[146]
synthetizedthermo-responsiveplasma-polymerizedpoly(N-isopropylacrylamide)orN-vinylcaprolactam
films. Muzammil et al. [147] reported on the pH-responsive coatings prepared by the plasma
co-polymerizationofacrylicacidandoctafluorocyclobutane. Althoughnoneofthealreadydeveloped
stimuli-responsiveplasmapolymerswereusedforthefabricationofAg-containingnanocomposites,
thisoptionstillshowsagreatdealofpromise.
Finally,ithastobementionedthatdespitethesubstantialandundisputableprogressinthefield
ofantibacterialAg/plasmapolymercoatingsandthelargeamountofsuggestedandtestedapproaches
that were briefly summarized in this review, to date the use of such materials still remains very
limited. Thisispartlyduetothelackofclinicalstudies,aswellasthenotyetstandardizedmethods
applied for evaluating the antibacterial effects of produced coatings. The latter relates both to the
choiceofbacteriaorproceduresusedforthequantificationofantibacterialeffectsthatmakesitalmost
impossibletocompareresultsreachedbydifferentgroups. Becauseofthis,thereisacleardemandto
propose/developstandardized,reliable,andhighthroughputvalidationmethodologiesfortesting
producedantibacterialcoatings,whichappliesnotonlytothecoatingsproducedbyplasma-based
methods but to other methods as well. In addition, all the experiments focused on determining
the antibacterial effects of produced Ag/plasma polymer coatings were performed invitro. It is
well-knownthatunderthemorerelevantinvivoconditionstheperformanceofproducedcoatings
maybelargelyaltered,e.g.,bythepossibleaccumulationofdeadbacteriaorproteinsonsurfacesof
producedcoatings. Furthermore,otherissuesrelatetofactorswhichareoftenoverlooked,suchas
wearresistance,long-termstability,theabilityofAg/plasmapolymernanocompositestowithstand
common sterilization procedures, or, in the case of implanted materials, to integrate well with a
hosttissue. However,theuseofplasma-basedtechniques—mostlikelyincombinationwithother
approaches—stillpresentsitselfasavividandauspiciousoptionfortheproductionofhighlyeffective
antibacterialcoatings.
5. Conclusions
Therehasbeenenormousprogressinsilver/plasmapolymernanocompositeantibacterialcoatings
inthelasttwodecades. Asshowninthispaper,numerousstrategieshavealreadybeentestedorare
underconsiderationfortheeffectiveproductionofsuchmaterials. However,despitepromisingresults,
thefieldofAg/plasmapolymerantibacterialcoatingsstillfacesmanychallenges,meaningthatbetter
understandingandcontrolofbactericideactivityofthepreparedcoatings,aswellasthedevelopment
ofnewmanufacturingprocedures,areneeded.
Author Contributions: Writing-Original Draft Preparation, A.K., J.K.; Writing-Review & Editing, O.K.;
Visualization,J.K.
Funding: ThisresearchwasfundedbyGrantAgencyofCzechRepublicgrantnumberGACˇR16-14024Sand
grantGAUK1394217fromGrantAgencyofCharlesUniversity.
ConflictsofInterest:Theauthorsdeclarenoconflictofinterest.
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