Polymeric Coatings with Antimicrobial Activity: a Short Review

Review Polymeric Coatings with Antimicrobial Activity: A Short Review

Ana C. Pinho and Ana P. Piedade *

Department of Mechanical Engineering, CEMMPRE, University of Coimbra, 3030-788 Coimbra, Portugal; [email protected] * Correspondence: [email protected]; Tel.: +351-239-790700

Received: 29 September 2020; Accepted: 23 October 2020; Published: 24 October 2020

Abstract: The actual situation of microorganisms resistant to antibiotics and pandemics caused by a virus makes research in the area of antimicrobial and antiviral materials and surfaces more urgent than ever. Several strategies can be pursued to attain such properties using diﬀerent classes of materials. This review focuses on polymeric materials that are applied as coatings onto pre-existing components/parts mainly to inhibit microbial activity, but polymer surfaces with biocidal properties can be reported. Among the several approaches that can be done when addressing polymeric coatings, this review will be divided in two: antimicrobial activities due to the topographic cues, and one based on the chemistry of the surface. Some future perspectives on this topic will be given together with the conclusions of the literature survey.

Keywords: antimicrobial polymeric coatings; surface topography; surface chemistry; monolithic coatings; polymer-based composites

1. Introduction There are several reasons why microorganisms, particularly bacteria, developed resistance to antibiotics: incorrect medical prescription [1], incompletion of appropriate antimicrobial therapy by the patient [2], overuse [3], extensive agricultural use [4], availability of few new antibiotics [5], and the overuse of antibacterial products for hygienic or cleaning purposes [6]. The fact is that, independently of the reason, researchers have devoted strenuous efforts in developing materials that can present antimicrobial and/or biocidal activity to overcome the stated problem. A wide range of medical components, more prone to bacterial infections and more serious consequences, are based on polymeric materials mainly due to their chemical stability, good mechanical properties, manufacturing versatility, and lower cost. Polymers are very versatile materials and, since long ago, have been modified to present additional properties/characteristics for different applications [7–9]. Nevertheless, by themselves or after some chemical modification, polymers can present antimicrobial properties, as described in many excellent papers, such as the one in ref [10]. However, often polymeric materials do not present the appropriate bulk properties that enable them to be applied in components/parts for structural engineering applications and invasive medical devices that require similar mechanical solicitations. In those situations, the polymer, monolithic, or composite, is used as a coating to confer to the surfaces of other materials the desired antimicrobial properties. This review focuses on this aspect, which explores both the topographic and chemistry cues used as strategies to prevent microbial adhesion and proliferation.

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2. Polymeric Coatings Several techniques can be used to produce coatings that are deposited onto a speciﬁc surface. The methodologies can be divided according to several approaches, considering if the deposition occurs at ambient conditions or under vacuum, according to the few given examples. Within the techniques used at ambient conditions, the simplest one usually involves the evaporation of the solute from a polymeric solution placed onto the desired substrate. Sometimes, the blade methodology can be used to control the amount of polymer onto the substrate [11]. This methodology is generally used for ﬂat substrates, whereas for the coating of complex three-dimensional substrates is usually achieved through dip coating [12] and spray [13] methods. Within the methodologies used at ambient conditions, spin coating produces polymeric coatings with high quality [14]. Among the techniques that are used under vacuum conditions for the deposition of polymeric coatings, two of the most cited in the literature are the chemical vapor deposition (CVD) [15] and the physical vapor deposition (PVD) [16]. The latest is considered one of the cleanest technologies for the deposition of coatings of any class material, as it does not involve any chemical or hazardous materials [17–19]. However, within this review, the emphasis will not be given to the technique but to the resulting polymeric coatings and their characterization, particularly their antimicrobial performance. This aim will be presented in the next sub-sections.

2.1. Topographic Cues A significant percentage of the available literature that studies the influence of the topographic cues onto the antimicrobial activity of polymers is not related to the roughness surface parameters of polymeric coatings. Instead, they describe the effect of engineered micro- and nano-features produced onto the surface of bulk polymers. Such is the case of surface engineered PEEK (polyetheretherketone) with cone/pillar-like micro/nano-arrays that mimic insect wings found to have antimicrobial activity. However, this behavior depended on the overall surface topography and dimensions of the surface structures [20]. Similar to this approach, several micro pattern architectures inspired in nature have been used to produce antimicrobial surfaces. Patterns, such as pits, pillars, ribs, channels, and ridges, are some examples engineered onto bulk surfaces [21]. If the only cue to be considered is the topographic one, only very few published articles use this type of approach. Most of the literature survey results in manuscripts were the influence of the topography is studied together with chemical modifications produced in the surfaces. One of the most recent works reports the plasma polymerization of the antibacterial polyterpenol onto several titanium substrates with different roughness at the nanoscale [22]. Nevertheless, the authors attribute the difference in the antibacterial properties, towards Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), to a heterogeneous chemical distribution of some chemical functional groups induced by the different topography. As reported in the paper, the topographic cues are not directly responsible for the more or less antimicrobial effect but induce different chemical surfaces responsible for the antibacterial effect. One other work highlighting the difficulty of establishing only the effect of topography onto the bacterial attachment was published by Pegalajar-Jurado and collaborators [23]. The authors used colloidal lithography and plasma polymerization, onto glass substrates, to produce periodic nanotopographies with controllable surface chemistry. The attachment of Escherichia coli (E. coli) onto carboxyl and hydrocarbon plasma polymer films both on flat and array surfaces was studied (Figure1). The authors concluded that surface chemistry played a critical role in bacterial attachment, whereas the exclusive effect of surface nanotopography was almost impossible to access. The influence of the topography on P. aeruginosa attachment was evaluated onto a polyimide biomedical film [24]. The authors induced micrometric periodic arrays of lines with 1, 2 and 10 µm period using Direct Laser Interference Patterning (DLIP). The authors find that the only the highest period was not able to inhibit bacterial adhesion. Polymers 2020,, 12,, x 2469 FOR PEER REVIEW 33 of of 15 14 Polymers 2020, 12, x FOR PEER REVIEW 3 of 15

Figure 1. ConfocalConfocal Laser Laser Scanning Scanning Microscopy Microscopy images images of of E.E. coli coli attachedattached to to glass glass ( (aa)) to to ppOct ppOct ( (bb)) and and Figure 1. Confocal Laser Scanning Microscopy images of E. coli attached to glass (a) to ppOct® (b) and toto ppAAc ppAAc ( c) after 18 hh ofof incubationincubation atat 3737 °C.C. BacteriaBacteria werewere stainedstained usingusingLIVE LIVE/DEAD/DEAD® BacLightBacLightTMTM to ppAAc (c) after 18 h of incubation at 37◦ °C. Bacteria were stained using LIVE/DEAD® BacLightTM Bacterial Viability kit. Green Green cells cells are considered alive, and red cells are consideredconsidered dead. Reprinted Bacterial Viability kit. Green cells are considered alive, and red cells are considered dead. Reprinted with permission from [23]. [23]. Copyri Copyrightght 2015, American Vacuum Society. with permission from [23]. Copyright 2015, American Vacuum Society. However, the results cannot be evaluated only co consideringnsidering the topographic topographic effect effect as the authors authors However, the results cannot be evaluated only considering the topographic effect as the authors indicateindicate thatthat the the DLIP DLIP processing processing also also induces induces chemical chemical changes changes in the surfacein the ofsurface the polymer. of the Moreover,polymer. indicate that the DLIP processing also induces chemical changes in the surface of the polymer. Moreover,they attribute they the attribute observed the degree observed of bacterial degree of colonization bacterial colonization to the different to the wettability different ofwettability the surface, of Moreover, they attribute the observed degree of bacterial colonization to the different wettability of thebut surface, they did but not correctthey did the not measured correct contactthe measured angle values contact considering angle values the di consideringfferent surface the roughness. different the surface, but they did not correct the measured contact angle values considering the different surfaceTherefore, roughness. once again Therefore, no unequivocal once again conclusions no un regardingequivocal theconclusions topographic regarding effect in the antimicrobialtopographic surface roughness. Therefore, once again no unequivocal conclusions regarding the topographic effectactivity in canthe beantimicrobial obtained. activity can be obtained. effect in the antimicrobial activity can be obtained. InIn a a recent work, a a polymer polymer coating coating was was sputtered sputtered onto onto the the surface surface of of an an elastomer, elastomer, In a recent work, a polymer coating was sputtered onto the surface of an elastomer, polydimethylsiloxane (PDMS), (PDMS), creating creating hierarch hierarchicalical micro- and nanowrinkled surfaces, and polydimethylsiloxane (PDMS), creating hierarchical micro- and nanowrinkled surfaces, and simultaneouslysimultaneously onto Si wafers to produce nanorough surfaces [[25]25] (Figure2 2).). simultaneously onto Si wafers to produce nanorough surfaces [25] (Figure 2).

Figure 2. Different surface morphology and topography, evaluated by SEM and AFM, of a polyamide Figure 2. Different surface morphology and topography, evaluated by SEM and AFM, of a polyamide coatingFigure 2. deposited Different ontosurface PDMS morphology (a,b) and and Si (c topography,) substrates. evaluated Reprinted by from SEM [25 and], published AFM, of bya polyamide MDPI. coating deposited onto PDMS (a,b) and Si (c) substrates. Reprinted from [25], published by MDPI. coating deposited onto PDMS (a,b) and Si (c) substrates. Reprinted from [25], published by MDPI. The coating was obtained from a polyamide target to promote a surface with a chemical composition The coating was obtained from a polyamide target to promote a surface with a chemical attractiveThe forcoating bacterial was colonization obtained from to evaluate a polyamide the true ta effrgetect ofto topography. promote a Insurface this study, with four a chemical bacterial composition attractive for bacterial colonization to evaluate the true effect of topography. In this strainscomposition were used: attractive two Gram-negative for bacterial colonizationE. coli, P. aeruginosa to evaluate, and twothe Gram-positivetrue effect of S.topography. aureus and BacillusIn this study, four bacterial strains were used: two Gram-negative E. coli, P. aeruginosa, and two Gram- subtilisstudy, (B.four subtilis) bacterial. It wasstrains found were that, used: regardless two Gram-negative of the bacterial E. strain, coli, onlyP. aeruginosa nano-topographic, and two features Gram- positive S. aureus and Bacillus subtilis (B. subtilis). It was found that, regardless of the bacterial strain, presentpositive lessS. aureus density and of Bacillus attached subtilis bacteria (B. (Figuresubtilis)3.). It was found that, regardless of the bacterial strain, only nano-topographic features present less density of attached bacteria (Figure 3). only Thisnano-topographic study shows that,features in what present concerns less density topographic of attached cues whenbacteria the (Figure surface 3). presents attractive This study shows that, in what concerns topographic cues when the surface presents attractive chemistry,This study higher shows surface that, roughness in what parametersconcerns topographic increase the cues probability when the of surface bacterial presents colonization attractive and chemistry, higher surface roughness parameters increase the probability of bacterial colonization and biofilmchemistry, formation. higher surface This fact roughness is a consequence parameters of theincrease similarity the probability between the of bacterial morphology colonization/topography and biofilm formation. This fact is a consequence of the similarity between the morphology/topography ofbiofilm the extracellularformation. This matrix fact is and a consequence nano and microroughnessof the similarity between in opposition the morphology/topography to surfaces with only of the extracellular matrix and nano and microroughness in opposition to surfaces with only nanotopographicof the extracellular profile. matrix and nano and microroughness in opposition to surfaces with only nanotopographic profile. nanotopographicMoreover, another profile. problem arises as determining surface topography importance is still not Moreover, another problem arises as determining surface topography importance is still not accurate,Moreover, considering another the problem complex arises interactions as determinin betweeng bacteria surface andtopography surfaces [importance26,27]. is still not accurate, considering the complex interactions between bacteria and surfaces [26,27]. accurate, considering the complex interactions between bacteria and surfaces [26,27].

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Figure 3. SEM micrographs of the polyamide thin film deposited onto PDMS and Si after the incubation Figure 3. SEM micrographs of the polyamide thin film deposited onto PDMS and Si after the with bacterial strains in solid medium (white bars = 5 µm; red & white bar = 2 µm). Reprinted from [25], incubation with bacterial strains in solid medium (white bars = 5 µm; red & white bar = 2 µm). published by MDPI. Reprinted from [25], published by MDPI. 2.2. Chemical Action 2.2. Chemical Action In opposition to the number of works reported in the literature regarding the influence of the topographicIn opposition cues of to polymeric the number coatings of works on the reported microbial in the activity, literature when regarding the subject the is influence focused onof thethe chemistrytopographic of thecues surface, of polymeric a significant coatings number on the of microbial published activity, research when is available. the subject is focused on the chemistryHybrid of polymericthe surface,/metal a significant coatings numb haveer been of published widely reported research in is theavailable. late years. Usually, these coatingsHybrid include polymeric/metal metal ions or nanoparticles, coatings have which been arewidely impregnated reported in in the the coating late years. for further Usually, release these or notcoatings to conduct include the metal antimicrobial ions or nanoparticles, activity [28]. Silverwhich is are by impregnated far the most studied in the coating metal in for such further approaches release sinceor not its to antimicrobial conduct the properties antimicrobial are well activity established [28]. Silver for a is wide by rangefar the of most microorganisms studied metal [29 ].in such approachesIn a study since conducted its antimicrobial by Pishbin properties et al., Ag are NPs well were established encapsulated for a wide into arange composite of microorganisms formulation of[29]. chitosan and bioactive glass to coat 316 stainless steel samples, by a single-step electrophoretic depositionIn a study (EPD), conducted for orthopedic by Pishbin applications et al., Ag [ 30NPs]. Besideswere encapsulated helping to avoid into a thecomposite initial burst formulation release, theof chitosan encapsulation and bioactive of the nanoparticles glass to coat also 316 hinders stainless possible steel environmentalsamples, by a hazardssingle-step associated electrophoretic with the releasedeposition of Ag (EPD), NP. However, for orthopedic although applications the coatings [30]. proved Besides to be helping efficient to towards avoid theS. aureusinitial upburst to 10release, days, thethe concentrationencapsulation of of Ag the NPs nanoparticles revealed to also be cytotoxic hinders possible to osteoblast-like environmental cells up hazards to 7 days associated [30]. Further with studiesthe release are proposedof Ag NP. in However, order to refinealthough the correctthe coatings concentration proved to of be the efficient Ag NP. towards In a different S. aureus approach, up to the10 days, antimicrobial the concentration ability of of PET Ag coated NPs revealed and uncoated to be cytotoxic surfaces wasto osteoblast-like evaluated against cells up bacteria. to 7 days Herein, [30]. PETFurther meshes studies were are coated proposed with in a order polyacrylic to refine acid the/Ag correct NPs formulationconcentration by of a the plasma Ag NP. polymerization In a different approach, the antimicrobial ability of PET coated and uncoated surfaces was evaluated against bacteria. Herein, PET meshes were coated with a polyacrylic acid/Ag NPs formulation by a plasma

Polymers 2020, 12, 2469 5 of 14 Polymers 2020, 12, x FOR PEER REVIEW 5 of 15 polymerizationtechnique [31]. Beforetechnique the [31]. coating Before procedure, the coating the Agprocedure, NPs were the entrapped Ag NPs were into theentrapped polyacrylic into acidthe polyacrylicpolymeric network. acid polymeric After 24 network. h, the coated After meshes24 h, the presented coated meshes a visible presented inhibition a visible halo towards inhibitionS. aureus halo towardsand E. coli S. comparedaureus and to E. the coli uncoated compared PET to the mesh uncoated (Figure 4PET). mesh (Figure 4).

Figure 4.4. AntibacterialAntibacterial analysis analysis of Agof Ag loaded loaded and controland control PET meshes: PET meshes: (a) S. aureus (a) S.;( baureus) E. coli; .(b Reprinted) E. coli. Reprintedfrom [31], withfrom permission[31], with permission from Elsevier. from Elsevier. No bacterial growth reduction was observed for the uncoated meshes. Another approach No bacterial growth reduction was observed for the uncoated meshes. Another approach describes the preparation of a polyacrylate-based hydrogel with Ag NPs to coat titanium implants, describes the preparation of a polyacrylate-based hydrogel with Ag NPs to coat titanium implants, by electrosyntherization [32]. The antimicrobial activity of the coatings was tested using the most by electrosyntherization [32]. The antimicrobial activity of the coatings was tested using the most common pathogens in orthopedic infections. Besides, the interaction with osteoblasts was also assessed. common pathogens in orthopedic infections. Besides, the interaction with osteoblasts was also The results show that tuning of the Ag ion release was conducted properly since the coatings were able assessed. The results show that tuning of the Ag ion release was conducted properly since the to maintain the antimicrobial activity without causing any harm or negative response to the osteoblasts coatings were able to maintain the antimicrobial activity without causing any harm or negative present at the implant interface. The release of Ag NPs caused some concerns about their possible response to the osteoblasts present at the implant interface. The release of Ag NPs caused some toxic behavior towards the cell, unlike Ag ions [33]. concerns about their possible toxic behavior towards the cell, unlike Ag ions [33]. Following this route, a research team proposed a coating production that allows the release of Ag Following this route, a research team proposed a coating production that allows the release of ions while maintaining the Ag NPs attached to the network to reduce toxicity [34]. The stabilization Ag ions while maintaining the Ag NPs attached to the network to reduce toxicity [34]. The of the Ag NPs was achieved by their incorporation into a poly(butyl acrylatemethyl methacrylate) stabilization of the Ag NPs was achieved by their incorporation into a poly(butyl acrylatemethyl copolymer. This formulation was then used to coat glass slides by a dip coat technique. After six days, methacrylate) copolymer. This formulation was then used to coat glass slides by a dip coat technique. the coatings proved to maintain the Ag NPs while releasing silver ions to the surrounding media. After six days, the coatings proved to maintain the Ag NPs while releasing silver ions to the To coat Ti screws for biomedical applications, silver nanoparticles were embedded into a PP-g-PEG surrounding media. To coat Ti screws for biomedical applications, silver nanoparticles were graft copolymer [35]. After the coating formulations were complete, the Ti screws were dipped into the embedded into a PP-g-PEG graft copolymer [35]. After the coating formulations were complete, the solution and dried for 5 min. This last step was repeated 20 times until a film was covering the screw. Ti screws were dipped into the solution and dried for 5 min. This last step was repeated 20 times The antimicrobial effect was determined by the exposure to S. aureus, showing promising results. After until a film was covering the screw. The antimicrobial effect was determined by the exposure to S. 21 days of implantation, the screws were able to maintain Ag NPs attached to their surface showing aureus, showing promising results. After 21 days of implantation, the screws were able to maintain that the coating was resistant to the tapping forces to which the screws were susceptible. Ag NPs attached to their surface showing that the coating was resistant to the tapping forces to which Using a sol-cast method, new chitosan/Ag/ZnO composite films were prepared for coating glass the screws were susceptible. slides [36]. After the Ag NPs impregnation, it was possible to observe that the particles presented a Using a sol-cast method, new chitosan/Ag/ZnO composite films were prepared for coating glass granular and spherical morphology and were uniformly distributed along the composite film. In what slides [36]. After the Ag NPs impregnation, it was possible to observe that the particles presented a concerns the antimicrobial tests, a wide range of bacteria was used. After the tests, it was possible to granular and spherical morphology and were uniformly distributed along the composite film. In conclude that the chitosan/Ag/ZnO coatings presented higher antimicrobial activity than chitosan/ZnO what concerns the antimicrobial tests, a wide range of bacteria was used. After the tests, it was and chitosan/Ag films. This fact proves that the antimicrobial effect is enhanced by incorporating possible to conclude that the chitosan/Ag/ZnO coatings presented higher antimicrobial activity than Ag and ZnO together within the chitosan polymeric network [36]. The initial color of chitosan is not chitosan/ZnO and chitosan/Ag films. This fact proves that the antimicrobial effect is enhanced by significantly affected by the incorporation of Ag and ZnO. incorporating Ag and ZnO together within the chitosan polymeric network [36]. The initial color of To avoid the use of silver nanoparticles, Tzanov et al. described the preparation of hybrid chitosan is not significantly affected by the incorporation of Ag and ZnO. chitosan/ZnO coatings for cotton fabrics [37]. In this work, the deposition of both ZnO nanoaprticles To avoid the use of silver nanoparticles, Tzanov et al. described the preparation of hybrid and chitosan was performed by a sonochemical technique. The ZnO concentration in the film chitosan/ZnO coatings for cotton fabrics [37]. In this work, the deposition of both ZnO nanoaprticles and ultrasound irradiation time (processing time) were varied to achieve the highest antibacterial and chitosan was performed by a sonochemical technique. The ZnO concentration in the film and ultrasound irradiation time (processing time) were varied to achieve the highest antibacterial

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Polymers 2020, 12, x FOR PEER REVIEW 6 of 15 eﬀectiveness without being cytotoxic. Figure5 displays the morphology of the cotton fabric coated effectiveness without being cytotoxic. Figure 5 displays the morphology of the cotton fabric coated with ZnO/chitosan coatings. with ZnO/chitosan coatings.

FigureFigure 5. 5.SEM SEM micrographs micrographs of of cotton cotton fabricfabric coatingcoating with ZnO/chitosan ZnO/chitosan coating. coating. In In the the right right image image the the arrowsarrows show show the the size size of of the the ZnO ZnO nanoparticles. nanoparticles. ReprintedReprinted with with permission permission from from [37]. [37 ].Copyright Copyright 2016 2016 AmericanAmerican Chemical Chemical Society. Society.

InIn what what concerns concerns the the antimicrobial antimicrobial activityactivity of th thee coated coated cotton cotton fabric, fabric, the the most most effective effective coating coating waswas achieved achieved for for 30 30 min min depositiondeposition time and and 2 2 mM mM concentration concentration of ofZnO ZnO NPs. NPs. The Theincorporation incorporation of ofchitosan enhanced enhanced the the final final biocom biocompatibilitypatibility of of the the coatings coatings avoiding avoiding the the possibility possibility for for them them to to become harmful for human health. Concomitantly, the coatings containing chitosan displayed become harmful for human health. Concomitantly, the coatings containing chitosan displayed superior superior antimicrobial potential against S. aureus and E. coli. Hospital laundry conditions were antimicrobial potential against S. aureus and E. coli. Hospital laundry conditions were simulated by simulated by multiple washing cycles at 75 °C to assess its influence on the antimicrobial properties multiple washing cycles at 75 C to assess its influence on the antimicrobial properties of the coatings. of the coatings. Results show◦ that chitosan improved the durability of the antimicrobial effect. The Results show that chitosan improved the durability of the antimicrobial effect. The final cytotoxicity of final cytotoxicity of the coating was also positively influenced by the incorporation of chitosan since thechitosan/ZnO coating was alsocoatings positively presented influenced higher byfibrobl theast incorporation viability in ofcomparison chitosan sincewith chitosanZnO coatings./ZnO coatings presentedComposite higher fibroblastAg NPs/alginate viability coatings in comparison were applied with to ZnO the coatings.cotton fabric to study the antibacterial activityComposite of the Agcoated NPs fabric/alginate throughout coatings successive were applied washes to the[38]. cotton In the fabric coating to formulation, study the antibacterial alginate activityplays oftwo the roles, coated as it fabric is concomitantly throughout the successive reducing washes and stabilizer [38]. In agent the coating of the metal formulation, nanoparticles. alginate playsThe twocoating roles, procedure as it is concomitantly consisted of the the immersion reducing of and the stabilizerfabrics into agent the coating of the mixture, metal nanoparticles. following Theby coating padding, procedure drying at consisted 75 °C for of15 the min, immersion and lastly of, the the curing fabrics process into the at coating120 °C for mixture, 3 min. followingAgainst E. by padding,coli, S. aureus drying, and at 75 P.◦ Caeruginosa for 15 min,, the and coated lastly, fabrics the curing demonstrated process atpr 120omising◦C for antibacterial 3 min. Against activity.E. coli , S. aureusHowever,, and withP. aeruginosa successive, the washing, coated the fabrics antibact demonstratederial potential promising suffered antibacteriala slight decrease activity. [38]. However, with successiveAnother washing,study reports the antibacterial the coatings potential of nylon su andffered silk a slightfibers decrease by a layer-by-layer [38]. dipping technique.Another studyMultilayers reports of the poly coatings (diallyldimethylammonium of nylon and silk fibers bychloride) a layer-by-layer (PDADMAC) dipping and technique. silver Multilayersnanoparticles of polypre-capped (diallyldimethylammonium in poly (methacrylic acid) chloride) (PMA) (PDADMAC)constituted the andfinal silverfiber coating nanoparticles [39]. pre-cappedFigure 6 shows in poly the (methacrylic fibers after 20 acid) cycles (PMA) of dipping. constituted the final fiber coating [39]. Figure6 shows the fibers after 20 cycles of dipping. After coating solution preparation and dipping of the nylon and silk fibers, the antimicrobial potential was assessed using S. aureus. Results show that there was ca. 80% bacteria reduction on coated silk fibers and around 50% reduction for the coated nylon fibers. Even though these coatings seem to be more effective for silk fibers, it is suggested that this technique could be useful for the design and manufacture of both synthetic and natural fibers with antimicrobial properties.

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Figure 6. SEM micrographies of fibers coated with 20 cycles of dipping into PDADMAC and PMA capped Ag NPs: (A) nylon; (B) and (C) silk. Reprinted from [39], with permission from Elsevier.

After coating solution preparation and dipping of the nylon and silk fibers, the antimicrobial potential was assessed using S. aureus. Results show that there was ca. 80% bacteria reduction on coated silk fibers and around 50% reduction for the coated nylon fibers. Even though these coatings seem to be more effective for silk fibers, it is suggested that this technique could be useful for the Figure 6. SEMSEM micrographies micrographies of offibers fibers coated coated with with 20 cycles 20 cycles of dipping of dipping into PDADMAC into PDADMAC and PMA and design and manufacture of both synthetic and natural fibers with antimicrobial properties. PMAcapped capped Ag NPs: Ag ( NPs:A) nylon; (A) nylon; (B) and (B )(C) and silk. (C) Reprintedsilk. Reprinted from from[39], with [39], permission with permission from fromElsevier. Elsevier. Using a different approach, polytetrafluorethylene (PTFE)/polyamide (PA)/Ag composite coatings,Using produced a different by approach, PVD, were polytetrafluorethylene deposited onto PTFE (PTFE) substrates/polyamide [40]. (PA)In this/Ag work, composite the coatings coatings, After coating solution preparation and dipping of the nylon and silk fibers, the antimicrobial wereproduced tested by against PVD, one were of deposited the most hazardous onto PTFE microorganisms substrates [40]. responsible In this work, for the nosocomial coatings were infections: tested potential was assessed using S. aureus. Results show that there was ca. 80% bacteria reduction on P.against aeruginosa one of. theThe most incorporation hazardous microorganismsof PA in the responsiblecoating formulation for nosocomial helped infections: to decreaseP. aeruginosa the . coated silk fibers and around 50% reduction for the coated nylon fibers. Even though these coatings hydrophobicityThe incorporation of ofthe PA PTFE in the subs coatingtrates. formulation Besides, when helped Ag to decreasewas added, the hydrophobicitythe surface of the of the coating PTFE seem to be more effective for silk fibers, it is suggested that this technique could be useful for the assumedsubstrates. a negative Besides, whenvalue Agof zeta was potential added, the and surface a high of polar the coating component assumed of the a negativesurface energy. value of With zeta design and manufacture of both synthetic and natural fibers with antimicrobial properties. thepotential release and of Ag a high ions, polar the componentcoating acquired of the antimicrobial surface energy. properties, With the releasewhich proved of Ag ions, to be the effective coating Using a different approach, polytetrafluorethylene (PTFE)/polyamide (PA)/Ag composite againstacquired P. antimicrobialaeruginosa (Figure properties, 7). which proved to be effective against P. aeruginosa (Figure7). coatings, produced by PVD, were deposited onto PTFE substrates [40]. In this work, the coatings were tested against one of the most hazardous microorganisms responsible for nosocomial infections: P. aeruginosa. The incorporation of PA in the coating formulation helped to decrease the hydrophobicity of the PTFE substrates. Besides, when Ag was added, the surface of the coating assumed a negative value of zeta potential and a high polar component of the surface energy. With the release of Ag ions, the coating acquired antimicrobial properties, which proved to be effective against P. aeruginosa (Figure 7).

FigureFigure 7. 7. SEMSEM images images of of PTFE/PA PTFE/PA coating coating with with P.P. aeruginosa aeruginosa (left(left);); PTFE/PA PTFE/PA with with silver silver (middle (middle);); inhibitioninhibition halo halo formed formed fo forr PTFE/PA PTFE/PA with with silver silver (right (right). Reprinted). Reprinted from from[40], with [40], permission with permission from Elsevier.from Elsevier.

MultilayerMultilayer thinthin films films made made from from a mixture a mixture of poly(allylamine of poly(allylamine hydrochloride) hydrochloride) (PAH), poly(acrylic (PAH), poly(acrylicacid) (PAA) andacid) polyacrylamide (PAA) and polyacrylamide (PAAm), (PAH (PAAm),/PAA/PAAm), (PAH/PAA/PAAm), with Ag nanoparticles with Ag were nanoparticles synthetize wereto coat synthetize planar surfacesto coat planar and magneticsurfaces and colloidal magnetic particles colloidal to evaluateparticles to the evaluate antibacterial the antibacterial effect [41]. Figure 7. SEM images of PTFE/PA coating with P. aeruginosa (left); PTFE/PA with silver (middle); effectThe influence [41]. The ofinfluence the thickness of the thickness of the entire of the film entire and film the and concentration the concentration of Ag nanoparticlesof Ag nanoparticles in the inhibition halo formed for PTFE/PA with silver (right). Reprinted from [40], with permission from inantibacterial the antibacterial properties properties was also was assessed. also assessed. Results Results suggest suggest that the that inhibition the inhibition halo increases halo increases with the Elsevier. withincrease the increase of Ag concentration of Ag concentration in the film. in the In film. addition, In addition, the release the release of silver of into silver the into surrounding the surrounding media mediaoccurs occurs by oxidation by oxidation of the of surface the surface of the of nanoparticles. the nanoparticles. The The magnetic magnetic microspheres microspheres coated coated with with the Multilayer thin films made from a mixture of poly(allylamine hydrochloride) (PAH), thedescribed described films films were were suggested suggested as possibleas possible antibacterial antibacterial deliver deliver agents agents towards towards precise precise locations. locations. poly(acrylic acid) (PAA) and polyacrylamide (PAAm), (PAH/PAA/PAAm), with Ag nanoparticles Besides silver, copper nanoparticles have also been studied for antimicrobial purposes. were synthetize to coat planar surfaces and magnetic colloidal particles to evaluate the antibacterial The possibility to coat stainless steel devices with a poly(ethylene glycol diacrylate)/copper-based effect [41]. The influence of the thickness of the entire film and the concentration of Ag nanoparticles nanoparticles hydrogel was described elsewhere [42]. The coatings were attached to the substrates by in the antibacterial properties was also assessed. Results suggest that the inhibition halo increases fast and straightforward electrochemical polymerization. Antimicrobial tests using S. aureus and E. coli with the increase of Ag concentration in the film. In addition, the release of silver into the surrounding demonstrated the ability of the CuNPs-PEGDA coatings to inhibit the growth of the studied bacteria. media occurs by oxidation of the surface of the nanoparticles. The magnetic microspheres coated with the described films were suggested as possible antibacterial deliver agents towards precise locations.

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Besides silver, copper nanoparticles have also been studied for antimicrobial purposes. The possibility to coat stainless steel devices with a poly(ethylene glycol diacrylate)/copper-based nanoparticles hydrogel was described elsewhere [42]. The coatings were attached to the substrates by fast and straightforward electrochemical polymerization. Antimicrobial tests using S. aureus and PolymersE. coli demonstrated2020, 12, 2469 the ability of the CuNPs-PEGDA coatings to inhibit the growth of the studied8 of 14 bacteria. More recently,recently, the the conjugation conjugation of polymeric of polymeric materials materials and copper and has copper been studiedhas been for antimicrobialstudied for purposesantimicrobial using purposes the metal using nanoparticle the metal approachnanoparticle and approach other processing and other techniques. processing Antechniques. example An of thatexample is the of work that conductedis the work by conducted Rtimi et al. by where Rtimi Cu-polyester et al. where (Cu-PES)Cu-polyester coatings (Cu-PES) are prepared coatings by are a sputteringprepared by technique a sputtering [43]. technique Herein, the [43] coatings. Herein, could the coatings inactivate couldE. coli inactivatewithin 45 E. min coliin within both anaerobic45 min in andboth aerobic anaerobic media and (Figure aerobic8). media The inactivation (Figure 8). The occurred inactivation not only occurred under low not intensityonly under visible low lightintensity but alsovisible for light dark but conditions. also for dark conditions.

a) b) c)

Figure 8. Live and dead bacteria onon Cu-PESCu-PES samples:samples: ((aa)) tt= = 0; (b) t = 3030 min; ( c) t = 6060 min min (low (low intensity light irradiation). Reprinted from [[43],43], with permission from DeDe Gruyter.Gruyter. Aside from incorporating metal ions or nanoparticles, there are studies where antimicrobial and Aside from incorporating metal ions or nanoparticles, there are studies where antimicrobial and antibacterial coatings were prepared only using polymeric materials. Due to its biocidal properties [44], antibacterial coatings were prepared only using polymeric materials. Due to its biocidal properties N,N-dodecylmethyl-polyethylenimine (PEI) received special attention and was included in a series of [44], N,N-dodecylmethyl-polyethylenimine (PEI) received special attention and was included in a studies. In a work conducted by Park et al., glass and polyethylene slides were dipped into PEI-based series of studies. In a work conducted by Park et al., glass and polyethylene slides were dipped into hydrophobic solutions [45]. After the dipping process, the solvent was removed by evaporation. PEI-based hydrophobic solutions [45]. After the dipping process, the solvent was removed by The coated samples were then incubated with S. aureus and E.coli. Results show that the coated slides evaporation. The coated samples were then incubated with S. aureus and E.coli. Results show that the were able to kill bacteria, probably due to the rupture of the cellular membranes. coated slides were able to kill bacteria, probably due to the rupture of the cellular membranes. Klibanov and co-workers published several works using PEI, where both formulation and coating Klibanov and co-workers published several works using PEI, where both formulation and procedures were evaluated. The use of linear and branched PEI and other PEI derivatives as a paint-like coating procedures were evaluated. The use of linear and branched PEI and other PEI derivatives as coating in glass slides was also reported [46,47]. The antibacterial action was validated by evaluating a paint-like coating in glass slides was also reported [46,47]. The antibacterial action was validated the antibacterial activity of the coatings in contact with S. aureus and E. coli. by evaluating the antibacterial activity of the coatings in contact with S. aureus and E. coli. In one of the most recent published studies, PEI was used to coat glass slides using a painting In one of the most recent published studies, PEI was used to coat glass slides using a painting technique. As a result, coatings proved to be lethal to both S. aureus and E. coli [46]. Following the technique. As a result, coatings proved to be lethal to both S. aureus and E. coli [46]. Following the paint-like coating approach, most recently, organo-soluble quaternary chitin polymers were synthesized paint-like coating approach, most recently, organo-soluble quaternary chitin polymers were to create bactericidal paint [48]. The immobilization of the prepared polycationic paint was achieved synthesized to create bactericidal paint [48]. The immobilization of the prepared polycationic paint without covalent bonding. The coatings proved to be eﬀective against drug-sensitive and drug-resistant was achieved without covalent bonding. The coatings proved to be effective against drug-sensitive bacteria. When in contact with the bacteria, the cationic polymers can break their cell membrane, and drug-resistant bacteria. When in contact with the bacteria, the cationic polymers can break their causing it to leach out its intracellular constituents. As a consequence of the leaching, the bacterial cell membrane, causing it to leach out its intracellular constituents. As a consequence of the leaching, cell dies. the bacterial cell dies. The preparation of a self-healing antimicrobial polymeric coatings is reported in the literature. The preparation of a self-healing antimicrobial polymeric coatings is reported in the literature. In a work, using a spin coating technique, multilayers of PEI and styrene maleic anhydride copolymer In a work, using a spin coating technique, multilayers of PEI and styrene maleic anhydride copolymer (SMA) were deposited onto PP-based substrates and then cured, as shown in Figure9[ 49]. Due to (SMA) were deposited onto PP-based substrates and then cured, as shown in Figure 9 [49]. Due to the composition of the coating, it was possible to tune several properties. The hydrophobic character the composition of the coating, it was possible to tune several properties. The hydrophobic character was conferred by the styrene subunits, while the antimicrobial potential was related to the cationic primary amine groups and chlorination of N-halamine formed groups. As a result, the coatings maintained their antimicrobial activity even when increasing the organic load conditions of E. coli. In addition, the coatings proved to have self-healing properties, after exposure to both acid and alkaline surrounding media, by being able to restore their characteristic chemical bonds under heat [49]. Polymers 2020, 12, x FOR PEER REVIEW 9 of 15 was conferred by the styrene subunits, while the antimicrobial potential was related to the cationic primary amine groups and chlorination of N-halamine formed groups. As a result, the coatings maintained their antimicrobial activity even when increasing the organic load conditions of E. coli. In

Polymersaddition,2020 the, 12 ,coatings 2469 proved to have self-healing properties, after exposure to both acid and alkaline9 of 14 surrounding media, by being able to restore their characteristic chemical bonds under heat [49].

Figure 9. Schematic representation of the preparation of the PEI/SMA coating. Reprinted from [49], Figure 9. Schematic representation of the preparation of the PEI/SMA coating. Reprinted from [49], with permission from Elsevier. with permission from Elsevier. The same group investigated the antimicrobial potential of PEI/SMA multilayer coatings on PP The same group investigated the antimicrobial potential of PEI/SMA multilayer coatings on PP based substrates with the variation of SMA molecular weight [50]. Furthermore, the storage stability based substrates with the variation of SMA molecular weight [50]. Furthermore, the storage stability was also evaluated. Before coating, the PP substrates were activated in order to enhance the binding of was also evaluated. Before coating, the PP substrates were activated in order to enhance the binding the coating. Square substrates were exposed to UV-Ozone irradiation (UVO) to promote the formation of the coating. Square substrates were exposed to UV-Ozone irradiation (UVO) to promote the of carboxylic acid groups by a photo-oxidation reaction. Then, to create anhydride groups on its formation of carboxylic acid groups by a photo-oxidation reaction. Then, to create anhydride groups surface, the substrates reacted with 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ). This step on its surface, the substrates reacted with 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ). intended to turn the surface of the PP substrate more reactive when in contact with the primary amine This step intended to turn the surface of the PP substrate more reactive when in contact with the groupsPolymers 2020 of PEI., 12, Thex FOR activation PEER REVIEW and coating of PP substrates are represented in Figure 10. 10 of 15 primary amine groups of PEI. The activation and coating of PP substrates are represented in Figure 10.

FigureFigure 10.10. Representation of the activation of PP substratessubstrates and further coating. Reprinted from [50], [50], withwith permissionpermission fromfrom Elsevier.Elsevier.

Results show that the molecular weight of SMA influenced the surface energy of the coating [49]. With the increase of the SMA molecular weight, the surface energy decreased. Among the different molecular weights studied, the SMA with the lowest molecular weight (6 kDa) originated films with enhanced biocidal activity against E. coli. In a different approach, using electrochemical deposition, coatings of polypyrrole (PPy) and PPy/PEG were deposition on novel titanium allow electrode [51]. This work proved that the composite coatings were more effective against E. coli than the single PPy coating. Besides, the surface characteristics of the composite PPY/PEG coating seem to be the critical factor in the inhibition of E. coli. The preparation of PPy coatings with both antimicrobial and electrical properties was suggested elsewhere [52]. PPy was deposited on stainless steel substrates by an electrodeposition technique. However, to activate the antimicrobial effect of PPy, after the deposition, the prepared coating was treated with chlorine bleach. As a result, the final coating was a N-halamine based PPy (Figure 11). When in contact with S. aureus, the prepared coating could inactive the bacteria after 60 s for more than one test cycle. Therefore, it can be concluded that the coating effectiveness was not affected by a first cycle in contact with the bacteria. Multifunctional coatings for protecting steels in harsh environments were examples of applications suggested for the prepared coatings [52].

Polymers 2020, 12, x FOR PEER REVIEW 10 of 15

Polymers 2020, 12, 2469 10 of 14 Figure 10. Representation of the activation of PP substrates and further coating. Reprinted from [50], with permission from Elsevier. Results show that the molecular weight of SMA influenced the surface energy of the coating [49]. Results show that the molecular weight of SMA influenced the surface energy of the coating [49]. With the increase of the SMA molecular weight, the surface energy decreased. Among the different With the increase of the SMA molecular weight, the surface energy decreased. Among the different molecular weights studied, the SMA with the lowest molecular weight (6 kDa) originated films with molecular weights studied, the SMA with the lowest molecular weight (6 kDa) originated films with enhancedenhanced biocidalbiocidal activity against against E.E. coli coli. . InIn aa didifferentfferent approach, using using electrochemical electrochemical deposition, deposition, coatings coatings of polypyrrole of polypyrrole (PPy) (PPy) and and PPyPPy/PEG/PEG werewere deposition deposition on on novel novel titanium titanium allow allo electrodew electrode [51]. [51]. This This work work proved proved that the that composite the coatingscomposite were coatings more were eff ectivemore effective against againstE. coli E.than coli than the the single single PPy PPy coating. coating. Besides, Besides, thethe surface surface characteristicscharacteristics of of the the composite composite PPY/PEG PPY/PEG coating coating seem seem to be tothe be critical the critical factor in factor the inhibition in the inhibition of E. ofcoli.E. coli. TheThe preparationpreparation of PPy PPy coatings coatings with with both both antimi antimicrobialcrobial and and electrical electrical properties properties was was suggested suggested elsewhereelsewhere [[52].52]. PPy PPy was was deposited deposited on on stainless stainless stee steell substrates substrates by byan anelectrodeposition electrodeposition technique. technique. However,However, toto activateactivate the antimicrobial antimicrobial effect effect of of PPy, PPy, after after the the deposition, deposition, the theprepared prepared coating coating was was treatedtreated withwith chlorinechlorine bleach. As As a a result, result, the the fina finall coating coating was was a N-halamine a N-halamine based based PPy PPy (Figure (Figure 11). 11). WhenWhen inin contact with with S.S. aureus aureus, ,the the prepared prepared coating coating could could inactive inactive the thebacteria bacteria after after 60 s 60for s for moremore thanthan oneone test cycle. Therefore, Therefore, it itcan can be be conc concludedluded that that the the coating coating effe ectivenessffectiveness was was not affected not affected byby aa firstfirst cyclecycle inin contactcontact with the the bacteria. bacteria. Mult Multifunctionalifunctional coatings coatings for forprotecting protecting steels steels in harsh in harsh environmentsenvironments werewere examples of of applications applications suggested suggested for for the the prepared prepared coatings coatings [52]. [52 ].

Polymers 2020, 12, x FOR PEER REVIEW 11 of 15 Figure 11. N-halamine based PPy coating preparation scheme [52]. Reprinted from Engineered ScienceFigure Publisher. 11. N-halamine based PPy coating preparation scheme [52]. Reprinted from Engineered

Science Publisher. As aforementioned, besides flat samples, other materials with different geometries, like fabrics, have alsoAs aforementioned, been tested with besides different flat samples, coatings other to increase materials their with antimicrobial different geometries, action. like In this fabrics, sense, anhave innovative also been N-halamine tested with chitosan different derivative coatings to was increase synthesized their antimicrobial and used toaction. coat In cotton this sense, fabric an [53 ]. Byinnovative dipping the N-halamine fabric into chitosan the polymeric derivative solution, was synt completehesized and coverage used to ofcoat the cotton fabric fabric was [53]. achieved By (Figuredipping 12). the fabric into the polymeric solution, complete coverage of the fabric was achieved (Figure 12).

FigureFigure 12. 12.SEM SEM images images of: of: ( A(A)) uncoated uncoated cottoncotton fabric, ( (BB)) coated coated cotton cotton fabric. fabric. Reprinted Reprinted from from [53], [53 ], withwith permission permission from from Elsevier. Elsevier.

The coated fabrics show to be able to inactive both S. aureus and E. coli within a contact time of 5 min. CVD deposition technique was used to create polymeric coatings on nylon fabric substrates [54]. Coatings up to 540 mg/cm2 of poly(dimethylaminomethyl styrene) were produced without affecting the color or the feel of the nylon fabric. No leaching from the fabric was observed. Following the ASTM E2149-01 standard, the coatings were tested for antimicrobial activity using E. coli and B. subtilis. Coatings with different concentrations were found to be very effective against both studied bacteria. Especially during the last decade, the study of innovative antimicrobial coatings acquired new routes of investigation base on multifunctional coating preparation and deposition. In a study conducted by Ming et al., polymeric coatings with both antifogging and antimicrobial function were synthetized, leading to semi-interpenetrating polymer networks (SIPN) [55]. These structures were constituted by quaternized poly(2-(dimethylamino)-ethyl methacrylate-co-methyl methacrylate) and polymerized ethylene glycol dimethacrylate. After the coating solution preparation, glass slides were coated by a spin coating technique. The dual functionality of the coatings was evaluated, and results show that the antifogging behavior was related to the hydrophilic/hydrophobic balance, while the antimicrobial effect derived from the hydrophobic quaternary ammonium compound, which was covalently bonded. The coatings proved to be effective in killing both Gram-positive Staphylococcus epidermidis (S. epidermidis) and Gram-negative E. coli. Moreover, it was concluded that the bacteria killing mechanism of the coatings is based on contact killing [55]. No leaching of bactericidal species was observed.

Polymers 2020, 12, 2469 11 of 14

The coated fabrics show to be able to inactive both S. aureus and E. coli within a contact time of 5 min. CVD deposition technique was used to create polymeric coatings on nylon fabric substrates [54]. Coatings up to 540 mg/cm2 of poly(dimethylaminomethyl styrene) were produced without affecting the color or the feel of the nylon fabric. No leaching from the fabric was observed. Following the ASTM E2149-01 standard, the coatings were tested for antimicrobial activity using E. coli and B. subtilis. Coatings with different concentrations were found to be very effective against both studied bacteria. Especially during the last decade, the study of innovative antimicrobial coatings acquired new routes of investigation base on multifunctional coating preparation and deposition. In a study conducted by Ming et al., polymeric coatings with both antifogging and antimicrobial function were synthetized, leading to semi-interpenetrating polymer networks (SIPN) [55]. These structures were constituted by quaternized poly(2-(dimethylamino)-ethyl methacrylate-co-methyl methacrylate) and polymerized ethylene glycol dimethacrylate. After the coating solution preparation, glass slides were coated by a spin coating technique. The dual functionality of the coatings was evaluated, and results show that the antifogging behavior was related to the hydrophilic/hydrophobic balance, while the antimicrobial effect derived from the hydrophobic quaternary ammonium compound, which was covalently bonded. The coatings proved to be effective in killing both Gram-positive Staphylococcus epidermidis (S. epidermidis) and Gram-negative E. coli. Moreover, it was concluded that the bacteria killing mechanism of the coatings is based on contact killing [55]. No leaching of bactericidal species was observed.

3. Conclusions and Future Perspectives From the presented bibliographic review, it can be concluded that the published work that reports only the topographic cues as the cause of the inhibition of bacterial adhesion and spread are few, and very often, contradictory results are described between different manuscripts. Usually, the topographic cues are reported along with the chemical action of materials that constitute the coatings. The significant percentages of work report the use of different chemical substances with the emphasis in the use of metals, such as silver, that confer to the polymeric surfaces the desired antimicrobial properties. Although this path can, in the short term, be presented as a solution in some very specific applications, several problems can arise from these approaches. Firstly, it is very controversial the optimal concentration of metallic material that can, simultaneously, present antimicrobial properties and provoke no harmful consequence to eukaryotic cells. Only very few works report in vitro studies with both types of cells to conclude about the true efficacy of the developed surfaces. Secondly, researchers in the field of genomics conclude that the metabolic pathways that induce metabolic resistance of the microorganisms towards antibiotics are the same that allow the microorganisms to develop resistance to metals. Therefore, it is only a matter of a short time before the approach considering metallic elements as antimicrobial agents is surpassed. Therefore, the authors believe that it is of the most urgency to begin to explore new paths for the development of new strategies for antimicrobial surfaces other than the incorporation of metallic (nano)particles.

Author Contributions: A.C.P. writing—original draft preparation, writing—review and editing. A.P.P. Conceptualization, writing—original draft preparation, writing—review and editing. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Acknowledgments: This work was partially supported by Foundation of Science and Technology of Portugal, Portugal 2020, Centro 2020, Compete 2020 and FEDER through projects UIDB/EMS/00285/2020 and MATIS-CENTRO-01-0145-FEDER-000014. Conﬂicts of Interest: The author declare no conﬂict of interest. Polymers 2020, 12, 2469 12 of 14

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