Scientia Iranica B (2019) 26(2), 808{814

Sharif University of TechnologyScientia Iranica

Transactions B: Mechanical Engineeringhttp://scientiairanica.sharif.edu

Plasma based surface modi�cation of poly(dimethylsiloxane) electrospun membrane proper fororgan-on-a-chip applications

A. Kiyoumarsioskoueia,b, M.S. Saidia,*, H. Moghadasa, and B. Firoozabadia

a. Department of Mechanical Engineering, Sharif University of Technology, 11365/8639, Tehran, Iran.b. Dalio Institute of Cardiovascular Imaging, Department of Radiology, Weill Cornell Medicine.

Received 1 January 2017; received in revised form 3 September 2017; accepted 13 January 2018

KEYWORDSElectrospun porousmembrane;Superhydrophilicsurfaces;Superhydrophobicsurfaces;Cell culture;Organ on a chip;Flexible membrane;Strong membrane;Surface modi�cations.

Abstract. Constructing of the sca�olds for cell culture applications has long been ofinterest for engineering researchers and biologists. In this study, a novel process is utilizedfor construction of suitable membrane with a high mechanical strength and appropriatesurface behavior. Poly (dimethylsiloxane) (PDMS) is electrospun in �ne �bers usingpoly (methyl methacrylate) (PMMA) as the carrier polymer in di�erent weight ratios.Since the surface behavior of all PDMS substrates is moderately hydrophobic (120 <Contact Angle (CA) < 150), the electrospun membranes with higher PDMS ratios showslightly higher hydrophilicity. Direct plasma treatment is utilized to change the interfacialwettability of the membrane. Applying plasma changes the surface energy and renders thePDMS/PMMA substrates superhydrophilic (CA < 5). In the following, the mechanicalproperties of the membrane are evaluated by the tensile test, and the results con�rm thesuitable mechanical strength of electrospun PDMS for cell culturing objectives (yield stressof more than 10 kPa). Also, changing the PDMS ratio does not signi�cantly a�ect thetotal sti�ness of the membrane. Thus, applying the proposed fabrication protocol providesa proper platform for cell viability and proliferation, which is proven by the results of MTTassay.© 2019 Sharif University of Technology. All rights reserved.

1. Introduction

Porous membranes are one of the inseparable parts ofmost of the \organ-on-a-chip" studies [1-3]. Also, inrecent years, the popularity of the electrospun sca�oldsin biomedical applications has been increased [4-7]since it is a cost-e�ective and very exible methodfor fabricating two and three-dimensional cell culturesca�olds [8-14]. Due to the �brous morphology ofelectrospun sca�olds, surface properties are signi�-

*. Corresponding author. Tel.: +98 66165558E-mail address: mssaidi@sharif.edu (M.S. Saidi).

doi: 10.24200/sci.2018.20148

cantly distinct compared with base polymer sheets.Indeed, surface roughness causes the Contact Angle(CA) to increase in electrospun hydrophobic polymersaccording to the Wenzel's theory. This phenomenonis not favorable in cell culture applications in mostof the experiments, because cells need to adhere tothe substrate. To address this problem, chemicalor electrochemical methods have been used to rendersuch sca�olds hydrophilic [15-17]. Lee et al. [15]used AA-grafted nano�bers to treat the electrospunpolyurethane nano�ber matrices surface. The resultscon�rmed that the contact angle of the AA-graftedtreated surface was 10 times smaller than the untreatedones. Collagen is another well-known natural polymer,which is commonly found in the extracellular matrix

A. Kiyoumarsioskouei et al./Scientia Iranica, Transactions B: Mechanical Engineering 26 (2019) 808{814 809

as it provides good adhesive properties, and has beenfrequently used in cell culture applications. Poliniet al. [18] functionalized the polymethylmethacrylate(PMMA) electrospun �bers sca�old with collagen bydi�erent methods of polymer coating. They demon-strated that the type of linking of collagen to thesurface played a more important role than the amountof coating of the collagen in cell adhesion property.More novel works in fabrication of the electrospun bio-membrane using other polymers than PDMS have beendone as well [19,20]. The mechanical properties andful�lling the tissue engineering requirements are theobjectives studied in the mentioned works.

Furthermore, other similar protocols as well asirradiation methods, known as photochemical modi�-cations, have been used [21-23]. Zhang et al. [24] usedUV radiation to change the hydrophobicity of the Poly(vinylidene uoride) (PVF) membrane. They showedthat contact angle could be decreased considerably byincreasing the radiation time.

From the structural point of view, the mechanicalstrength plays an important role in the cell culturingmembrane selection [25-27]. In most of the applica-tions, the membrane is better to be as thin as possiblewhile it also needs to have good resistance against themechanical stimulations [11]. Chen et al. [28] measuredthe Young modulus and ultimate tensile strength ofthe nano�bers and studied the e�ect of crosslinking onthe mechanical properties of the �brous membranes.The membrane tensile test was also done by Niu et al.[29] for single PDMS �bers and a �brous mat madeof Poly Vinyl Pyrrolidone (PVP). They showed thatelongation of the PDMS �ber mat was more thanthat of a single PDMS �ber; also, elongation of thesingle PDMS �ber was more than that of PDMS cast�lm. Previously, it was indirectly reported that aminimum of about 0.1 N for mechanical tensile strengthwas suitable for porous membranes in organ-on-a-chipapplications while the membranes thickness was morethan 10 �m [30,31].

To the best knowledge of the authors, the en-hancement of surface wettability of electrospun PDMSbase membranes to make them superhydrophilic, whichis appealing in cell culture applications, as well asthe quanti�cation of mechanical properties of suchsca�olds has not been investigated in the literature,which is the primary objective of the present paper.Already, similar studies have been done on PCL orsome other polymers [32]. In the present study, thegoal is improving the wettability of a prefabricatedsuperhydrophilic PDMS membrane in cell culture ap-plications. First, superhydrophobic porous �lms withdi�erent ratios of PDMS/PMMA are fabricated usingelectrospinning process. Then, a simple, yet robust,technique will be introduced to render the membranessuperhydrophilic. Finally, surface wettability as well

as mechanical properties of the fabricated electrospunmembranes will be investigated in details.

2. Materials and methods

The kit of SYLGARD® 184 silicone elastomer suppliedfrom Dow Corning Corporation was used as the basepolymer. Also, PMMA (MW 350000) supplied fromSigma-Aldrich Corporation was utilized as a carrierpolymer. Tetrahydrofuran (THF) was also suppliedfrom Sigma-Aldrich and used as the solver of the carriersolution. PDMS base polymer was mixed with its cur-ing agent with a ratio of 1:10 (Wt/Wt). PMMA/THFsolution was prepared with the ratio of 1:6 (Wt/Wt).Also, for cellular tests, human pulmonary alveolarepithelial cells were cultured in DMEM/F12 media,supplemented with 10% fetal bovine serum and 2%penicillin/streptomycin. The Human Epithelial LungCells (HELC) were cultured in two di�erent tests. Also,a material of a mixture of 5 mg/ml MTT solution in theRPMI environment (in 5 vials) was utilized for MTTassay.

2.1. Electrospinning procedureThe mixture of the PDMS and PMMA solutions wasprepared in di�erent weight ratios f0:1 1:1 2:1 3:14:1 5:1 6:1 all in Wt(PDMS)/Wt(PMMA)g and themembranes were fabricated by electrospinning method.The electrospinning process was conducted at thevoltage of 12 kV while the nozzle distance was adjustedat 15 cm. The polymer ow rate was set at about5 mL/min.

2.2. Surface characterizationThe quality and topographical features of all mem-branes were quanti�ed by Scanning Electron Mi-croscopy (SEM). JXA-840 electron microscopy modelof the Jeol Japan Company was used to this end.

2.3. Mechanical strength characterizationA load cell with the precession of 0.001 N in a tensiletesting machine of the houns�eld h10 ks model of testResources Company was used. Membrane sampleswere cut into rectangular samples with the size of about20 (mm)� 5 (mm). Hollow quadrangular paper frameswere built for better alignment of the samples to thesetup [33], as shown in Figure 1.

2.4. Contact angle measurementTo measure the contact angle, a manual setup compat-ible for putting the membrane was prepared.

A high-resolution horizontal camera was installedin front of the stage, and a light source was mountedon the backside. Figure 2 shows a schematic view ofthe contact angle measurement device.

810 A. Kiyoumarsioskouei et al./Scientia Iranica, Transactions B: Mechanical Engineering 26 (2019) 808{814

Figure 1. Quadrangular hollow paper for tensile testframe. This framework was utilized for mounting of thesamples on the machine.

Figure 2. Setup for measuring the contact angle. Thesyringe was schematic, and it could be replaced by pipette.

3. Results and discussion

The generated electrospun membranes exhibited goodappearance and were uniform. The Scanning ElectronMicroscopy (SEM) image of an electrospun membraneis shown in Figure 3.

3.1. Surface modi�cationThe applications of PDMS-based materials are signif-icantly increasing in biomedical sciences. Intrinsically,the polymer sheet is slightly hydrophobic (90 < CA <120) [34]. Using oxygen plasma has bene�cial e�ectson decreasing the contact angle and, subsequently,increasing the hydrophilicity. Widespread experiments

Figure 4. High-resolution image of distilled water dropleton (a) sheet of the PDMS, and (b) electrospun PDMSmembrane.

have shown decrease in the contact angle of about30�[35-37], which is helpful in micro uidic applications,but no work is found to report a reduction in contactangle to a highly hydrophilic phase.

The electrospinning of the polymer seems to in-crease hydrophobicity. Electrospinning changes poros-ity and roughness of the membrane, which is a validparameter in wettability [38]. Figure 4 displays thecontact angles in two di�erent conditions. This phe-nomenon could be explained using Wenzel's theory.According to the Wenzel's model, when the dropletsize is su�ciently larger than the surface roughness,increasing the roughness ratio causes increase in con-tact angle of the surface [39]. Although the porousproperty and the surface roughness of the electrospin-ning sca�olds are considered as suitable parameters,increasing the contact angle is a negative factor in celladhesion event. To modify the surface, plasma treatingprocedure was used. Two protocols were utilized.In the �rst procedure, the classical method of 1 minplasma exposure by plasma generator was used. In thesecond procedure, the exposure time was decreased to 7seconds, but the number of exposures was tripled (thisprotocol was obtained from about 200 trial and errortests). Figure 5 displays the e�ect of plasma treatmenton the electrospun PDMS membrane. Decreasing theexposure time does not provide enough time to modifythe surface of the membrane. On the other hand,increasing the exposure time causes a di�erent chemical

Figure 3. Scanning electron microscopy image of the electrospun PDMS membrane: (a) 1000� and (b) 10000�.

A. Kiyoumarsioskouei et al./Scientia Iranica, Transactions B: Mechanical Engineering 26 (2019) 808{814 811

Figure 5. Measured contact angle in di�erent conditions.Comparison of the contact angle before surfacemodi�cation was done with di�erent modi�ed surfaces.

reaction on the surface of �bers [40] and increase incarbonaceous in the surface, which is not a positiveevent in rendering the surface hydrophilic. Due to this,increasing the exposure number was proposed and usedin the new protocol.

According to the experiments, it is concludedthat change in the roughness of the surface, whichhappens due to electrospinning process, causes theslightly hydrophobic (90 < CA < 120) membranesto change into moderately hydrophobic (120 < CA <150) and even sometimes to superhydrophobic (150 <CA < 180) phases (as mechanical changes take placeon the membrane surface). This phenomenon is causedby changing surface roughness in micro scale whenthe �bers are accumulated in spinning. As describedbefore, changing the surface roughness causes thehydrophobicity of the membrane to increase (Wenzel'smodel). The o�ered protocol modi�es the hydrophobicsurfaces to hydrophilic phases and, consequently, thesuperhydrophobic surfaces to superhydrophilic ones.

3.2. Tensile testTensile tests were utilized to evaluate the e�ect ofPDMS concentrations on the mechanical behavior ofthe electrospun membrane. The ratios of the solu-tions are shown in Table 1. The yield strength andelongation of the membrane were measured for allseven samples, which are shown in Figures 6 and 7

Figure 6. The yield strength of the electrospunmembrane with di�erent PDMS percentages.

Figure 7. Elongation of the electrospun membrane withdi�erent PDMS percentages.

Table 1. Sample naming according to the ratio of thePDMS/PMMA.

Sample number Ratio of PDMS/P1VEMA

I 0:1

II 1:1

III 2:1

IV 3:1

V 4:1

VI 5:1

VII 6:1

for di�erent PDMS percentages. Considering thesetwo �gures, it could be concluded that the sti�nessand elongation of membrane are appropriate for cellculture applications and, consequently, for organ-on-a-chip applications according to references [41-44].

Table 1 shows the samples which were used forthe tensile test. Ratio of the PDMS/PMMA is shown.All the samples have the thickness of 50� 10 �m.

Also, it is observed that the mechanical behaviorof the membrane is not a linear function of the ratioof the PDMS. Although the spinning conditions andthe thickness where the �bers are bounded by eachother a�ect the mechanical sti�ness of the membraneand di�erent mechanical behaviors are observed, all thesamples are appropriate for organ-on-a-chip applica-tions [30,31,42].

3.3. CytocompatiblityThe capability of the membrane for culturing the cellsis compared with the classical cell cultures treated wellsby utilizing MTT assay. Since the MTT reagent wassensitive to light, the whole environment was isolatedfrom the light source. To do the assay, �rst, thecells medium was discharged from vials, then 400 �lof PRMI and 10 �l of MTT solutions were added tothe whole 24 well plates. The plates were placed inthe incubator for 24 hours. In the next step, the

812 A. Kiyoumarsioskouei et al./Scientia Iranica, Transactions B: Mechanical Engineering 26 (2019) 808{814

Figure 8. The cells aggregation evaluation using MTTassay (normalized to the maximum value of measurement).

MTT solution was aspirated o� and 1 ml of acidi�edisopropanol solution was replaced in each well (seeFigure 8).

Pipetting was done slowly and the well was putin the incubator for about 30 minutes. After doing thisprocedure, a 510 nm wavelength spectrophotometerwas used to measure the light intensity. The assayswere done three times and the results were averaged.The electrospun membrane provided a better conditionfor cell culturing. The intensity processing representedthe viability of the cells in the test. The results aredisplayed in Figure 8. They show that the cells havebetter viability and proliferation performance.

4. Conclusions

The electrospinning based fabrication of a exiblebeadless superhydrophobic membrane was reportedin this study. Electrospinning caused a remarkableincrease in hydrophobicity of the surface. This couldbe attributed to the increase in the roughness andcreation of nano-metric porosities on the surface of thepolymer. The results showed that physical increasein the hydrophobicity of the membrane enhanced thepotential of the surface going to a more hydrophilicphase using oxygen plasma treatment. Also, themechanical strength of the membrane was studiedas another important characteristic of the sca�olds.Although the strength of the membrane was not alinear function of the PDMS ratios, it was su�cientfor organ-on-a-chip applications.

The capability of the membrane for cell adhesionwas tested. The cells adhered to the membrane withoutusing any extracellular matrix polymers. Also, cellsviability was tested using MTT assay. Results showedthat the cells cultured on the electrospun membranehad about two times more aggregation capabilities.The cells could be alive and proliferate better than theones on the treated vials. Finally, this work showedthat manufacturing electrospun PDMS/PMMA mem-

brane was a fast, biocompatible, exible, and cost-e�ective method for cell culture and organ-on-a-chipapplications.

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Biographies

Amir Kiyoumarsioskouei received his BS and MSin Mechanical Engineering mainly working on environ-mental and energy researches. He started his PhD atSharif University of Technology in 2012 and extendedhis researches in Weill Cornell Medical College fromJune 2016. He did the fabrication and most ofexperiments in this work.

Mohammad Said Saidi is a Professor in Mechan-ical Engineering at Sharif University of Technology.He completed his PhD in Massachusetts Institute ofTechnology (MIT). He was the main manager and ideadeveloper in the recent work.

Hajar Moghadas received her BS and MS in Me-chanical Engineering. She started her PhD at SharifUniversity of Technology in 2012 and, due to herexpertise, she helped in the cell culture works in therecent work.

Bahar Firoozabadi is a Professor in MechanicalEngineering at Sharif University of Technology. Shecompleted her PhD at Sharif University. She was avery impressive consultant in the entire period of thisproject.