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Development and Characterization of a Hydrogel for Flexible and Stretchable Substrates

Marina ALBALADEJO SIGUAN, Roland FISCHER

Institute of Materials in Electrical Engineering 1, RWTH Aachen University, Sommerfeldstr. 24, 52074 Aachen, Germany

albaladejo@iwe1.rwth-aachen.de, fischer@iwe1.rwth-aachen.de

Abstract. The latest biomedical wearable electronics are being integrated on flexible and stretchable silicone substrates. These have proved a suitable integration with the curvy and dynamic surface of the human body [1]. The main challenge of the silicone-based substrates appears when using them in vivo and in vitro. Because of its hydrophobic properties and permeability of some gases, they can't provide the perfect environment for cells. For these reasons new materials are being researched. One promising material is the hydrogel, which has been one of the most important materials set for tissue engineering since many years.

In this paper a new hydrogel, synthesized with poly(ethylene glycol) diacrylate (PEGDA), poly(ethylene glycol) methacrylate (PEGMA) and trimethylolpropane tris(3-mercaptopropionate) (TMP3M), as crosslinker, has been engineered. The hydrogel presented shows a Young's modulus of 32.58 kPa and a rupture limit of 151% comparable to the mechanical properties of extra soft silicone substrates [2]. Good stability in different environments has been showed. Furthermore was demonstrated, with a Raman spectroscopy, that the crosslinking degree depends on the amount of mixed polymer solution.

Keywords Material engineering, Hydrogel, flexible substrates, wearable electronics.

1. Introduction With the new materials and technologies it is now possible to produce microstructures on flexible and stretchable substrates [2]. These structures give the possibility to control diseases and wounds, as well as a continuous monitoring of vital constants (blood pressure, pH, ECG, etc. [3]). The flexible substrates that have been produced in the last years are primarily silicone-based. But silicone has some disadvantages for being used in vivo and in vitro. It has been shown that silicone absorbs proteins to its surface [4]. Another issue is the permeability of oxygen and carbon dioxide, which could lead to drying of cells [5].

Because of these liabilities new materials have to be engineered.

Hydrogel has shown in the past years suitable properties for being used in tissue engineering. From one side it has a very similar structure to the macromolecular components of the skin, it allows the diffusion of nutrients or residues of the cells by diffusion, and provides a very good environment for cell growth [6]. It also offers more advantages than other polymer based substrates, such as very high water content, biocompatibility and simple control of the structural parameters [7]. With these properties, hydrogels are a very good option to develop smart skin.

Hydrogels have a large number of properties, but swelling and the mechanical properties are the most important ones for synthesizing a hydrogel that will be used as a substrate. The swelling and mechanical properties can be modified with the percentage of crosslinker or polymer concentration in the solution. By searching for a correlation between the properties and the product ratios, it is realized that for each hydrogel composition a different dependency is obtained. For these reason, the appropriate mixing percentage has to be found to achieve the suitable properties for the desired application. To achieve the good properties that the extra soft silicone substrates exhibit (Young's modulus: ≈50kPa, rupture limit: ≈80%) the long chained PEGDA polymer is chosen, because of the good mechanical properties that have been reported at ZHAO, X. et al. and Hahn, M. S. et al. among others. Owing to the high costs of this polymer, a combination of short chained PEGDA and PEGMA is used in this research. To crosslink both polymers and to reach a suitable polymer TMP3M, a three arm thiol functionalized crosslinker, is chosen.

In this paper, we will describe the synthesis and characterization of PEGDA-PEGMA-TMP3M hydrogels. A study on the dependency between the crosslinking ratio and the mixing volume will also be presented. Due to the engineered properties, the presented hydrogel may be used as a substrate for integration of stretchable electronics.

M. ALBALADEJO SIGUAN, R. FISCHER, 2 DEVELOPMENT AND CHARACTERIZATION OF A HYDROGEL FOR FLEXIBLE AND STRETCHABLE SUBSTRATES

2. Methods Engineering of the Hydrogel Polymer solution was prepared by mixing 675 µl 700 Mn PEGDA (Sigma Aldrich, 455008), 2,025 ml 500 Mn PEGMA (Sigma Aldrich, 409529) with 300 µl TMP3M (Sigma Aldrich, 381489) as crosslinker. The solution was gently mixed with a magnetic stirrer for one minute at 1000 r/min. Solutions were poured into molds and exposed to room light (568 lx) for ten hours.

Evaluation of Properties in Different Environments After the synthesis the samples had to be dialyzed. Through the process the samples were weighted, so that a characterization in water and at room conditions of the hydrogel could be made. Firstly the samples were submerged in a continuous flow of water for four hours. The hydrogels were weighted the first time, before putting them into the water, and after every hour. To make sure all the unlinked materials had left the hydrogel structure, the samples were left afterwards one day in purified water. After the washing process, the samples were left for ten days in the clean room with a temperature of 19.7°C and a relative humidity of 46%. The samples were weighted the first five days each day and at last the tenth day.

The weight ratio (WR) was described as:

0

0i

w w- w

=WR (1)

where wi is the weight after a certain time and w0 the weight of the sample after the synthesis.

Mechanical Properties Synthesized hydrogels were mechanically tested in a

mechanical testing machine Zwicki Z5.0 (Zwick/Roell). Five samples were tested using the DIN 53504 standart. Samples were synthesized as dogbones with a longitudinal area of 2x4 mm2. The tensile strain rate was 200 mm/min. The taken values included elastic modulus and rupture limit. The young modulus is measured in the linear region (between 0% and 15% strain) of the stress-strain plot (E = ∂σ/∂ε). Rupture limit is simply the elongation of the sample at the rupture point. To demonstrate a better comparison between the silicone and the hydrogel, we also tested samples from Polydimethylsiloxane (PDMS) with a mixing ratio of silicone to harder of 40:1.

Raman Spectroscopy The Raman spectroscopy was performed with the system RFS 100/S (Bruker Optics), using a Nd:YAG laser (1064 nm) with a power of 200 mW. For each spectrum 500 scans with a resolution of 4 cm-1 were collected.

In this case, five samples from hydrogel were synthesized and measured. Samples were synthesized with the same solution ratio as for the other samples, but the volume was varied. From a solution of 1 ml 1 sample was crosslinked, from a solution of 6 ml two samples were crosslinked, one with 5 ml and one with 1 ml. And from a solution of 11 ml were a sample of 1ml and a sample of 10 ml synthesized. All the samples were compounded in different petri dishes, so that every sample had the same height (1 mm).

3. Results Properties of the Hydrogel in Water and under Room Conditions Through the washing process from PEGDA-PEGMA-TMP3M hydrogels is seen that the samples swell in the first hours until they reached a maximum (see Fig. 1). During the day in purified water the samples show a loss of mass. This characterized the losing of unlinked materials through the diffusion to water. After they are taken out of water a linear mass loss can be estimated until aprox. 52 hours later. During the shrinking process, two steps can be observed. At the beginning the absorbed water evaporates out of the hydrogel structure (55 hours), subsequently the hydrogel dries. After 80 hours the samples reach a minimum and remain stable at room conditions, without losing the stretchable properties.

Fig. 1. Average weight ratio per time of five samples

It can be said that the synthesized hydrogel has good swelling properties, with an increase of aprox. 165% (water absorption of 225% minus the unlinked material loss of 60%) in their weight. After approximately two days the samples dries and reaches a stable state.

Mechanical Properties Figure 2 shows the average stress-strain correlation from PDMS and the PEGDA-PEGMA-TMP3M hydrogel. The PDMS strips fractured at a strain of 159% and the hydrogel at 151%, which are nearly equal. From the average of the five samples it can be appreciated that the PDMS shows a Young's modulus of 54.5 kPa which is

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superior as the one from the engineered hydrogel with an elastic modulus of 32.58 kPa in average.

Fig. 2. Strain-stress correlation of the average of five samples of PDMS and hydrogel

Raman Spectroscopy The first Raman spectroscopy was made to characterize the TMP3M and the solution of PEGDA-PEGMA. In Fig. 3 the prominent Raman shifts can be observed. In the PEGDA-PEGMA solution the band at 1648 cm-1 represents the stretching vibration of the C=C bound. The peak at 1725 cm-1 was for the stretching vibration of the C=O group [10]. The important Raman shifts from TMP3M are both thiol peaks, C-S vibration at 675 cm-1 and S-H vibration at 2575 cm-1, as well as the stretching vibration of the C=O group at 1738 cm-1 [11].

Fig. 3. Raman spectroscopy of TMP3M and PEGDA-PEGMA solution in arbitrary units (a.u.)

Two Raman shifts regions are important to analyze the crosslinking ratio from the compounded hydrogels. On the one hand the reduction of intensity from the thiol stretching vibrations due to the bond with the polymers. And on the other hand the variation of the stretching vibration from the C=C and C=O groups, due to the breakage of the bonds. It can be said that with a higher ratio of PEGMA as PEGDA in the solution, if the intensity is lower, more PEGMA would have been crosslinked and the more flexible and stretchable the sample will become.

Comparing the samples, it can be seen that almost every thiol group has been crosslinked (see Fig. 4) except for the sample of 1 ml solution. It was less crosslinked witch a "honey"-like consistence.

Fig. 4. Raman shifts region between 2450 cm-1 and 2675 cm-1 of

the five hydrogel samples in arbitrary units (a.u.)

Taking a closer look to the C=C and C=O vibration peaks (Fig. 5), the viscose state from the 1 ml sample, and the higher elasticity of the 1ml sample from the 11 ml solution rather than the 1 ml sample from the 6 ml solution is confirmed.

Fig. 5. Raman shifts region between 1550 cm-1 and 1800 cm-1 of

the 1ml samples in arbitrary units (a.u.)

Figures 6 and 7 show both samples from the same solution. It is realized that the samples have also a variation in intensity of the stretching vibration from the C=C and C=O groups. In this case the samples from the same solution didn't vary in their elasticity. The difference in intensity shows that the crosslinking of the samples differ between each other. It can be said that the crosslinking process is influenced by different crosslinked volume.

M. ALBALADEJO SIGUAN, R. FISCHER, 4 DEVELOPMENT AND CHARACTERIZATION OF A HYDROGEL FOR FLEXIBLE AND STRETCHABLE SUBSTRATES

Fig. 6. Raman shifts region between 1550 cm-1and 1800 cm-1 of

the samples from the 6 ml solution in arbitrary units (a.u.)

Fig. 7. Raman shifts region between 1550 cm-1 and 1800 cm-1 of

the samples from the 11 ml solution in arbitrary units (a.u.)

4. Conclusion The engineered hydrogel has, after the synthesis time, unlinked materials in its structure, so that a washing process is needed after cross-linking. After ten days at room conditions the hydrogel shows a good stability in his shape and weight. By testing the mechanical properties it is confirmed that the hydrogel is more flexible than the extra soft PDMS and has almost the same rupture limit. A chemical characterization of the main materials from the solution has been made by a Raman spectroscopy. Comparing the Raman shifts of the hydrogel samples it is noticed, that the quantity of solution and mold form have a correlation with the crosslinking process. But only the variation of the mixing solutions shows a correlation with the elasticity of the samples which also could easily be seen by optical inspection.

Overall characterization of different mixing ratios has to follow to get the best hydrogel substrate for smart skin applications.

The innovation of the presented hydrogel is the accomplishment of the synthesis of a non-liquid or brittle hydrogel. Furthermore this hydrogel shows very good mechanical properties, like elastic strain, so that it can be well compared with soft PDMS which is today state of the art for use as flexible and stretchable substrates. Regarding that and the advantages of hydrogels using them in vivo or in vitro the developed hydrogel should be considered as an

optimal material to use as a substrate in production of flexible and stretchable substrates like in smart skin applications.

Acknowledgements This research was supervised by apl. Prof. Dr.-Ing. U.

Schnakenberg and Prof. Dr. rer. nat. W. Mokwa. We also want to thank M.Sc. A. Töpel from the DWI Leibniz Institute for Interactive Materials in Aachen for the help and support during this project.

References [1] XU, L., GUTBROD, S. R., ROGERS, J. A. et al. 3D multifunctional

integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nature Communication, 2014, vol. 5, no. 3329.

[2] ZHOU, C. Flexible and Stretchable Gold Microstructures on Extra Soft Poly(dimethylsiloxane) Substrates. Advanced Material, 2015, vol. 27, p. 6664 – 6669

[3] XU, S., ZHANG, Y., ROGERS, J. A. Soft Microfluidic Assemblies of Sensors, Circuits, and Radios for the Skin. Science, 2014, vol. 344, no. 6179, p. 70 – 74.

[4] TOEPKE, M. W., BEEBE, D. J. PDMS Absorption of small Molecules and Consequences in Microfluidic Applications. Lab Chip, 2006, vol. 6, no. 12, p. 1484 - 1486.

[5] HANSEN, C. L., CLASSEN, S., BERGER, J. M., QUAKE, S. R. A Microfluidic Device for Kinetic Optimization of Protein Crystallization and In Situ Structure Determination. Journal of the American Chemical Society, 2006, vol. 128, no. 10, p. 3142 - 3143.

[6] LEE, K. Y., Mooney, D. J. Hydrogels for Tissue Engineering. Chemical Reviews, 2001, vol. 101, no. 7, p. 1869 - 1879.

[7] ZHU, J., ROGERS, E. Design Properties of Hydrogel Tissue-Engineering Scaffolds. Expert review of medical devices, 2011, vol. 8.5, p. 607 - 626.

[8] ZHAO, X. et al. Stretchable Hydrogel Electronics and Devices. Advanced Materials, 2015, vol. 28, no. 22, p. 4497 - 4505.

[9] HAHN, M. S. et al. Influence of Hydrogel Mechanical Properties and Mesh Size on Vocal Fold Fibroblast Extracellular Matrix Production and Phenotype. Acta biomaterialia, 2008, vol. 4.5, p. 1161 - 1171.

[10] LAMBERT, J.B. Introduction to Organic Spectroscopy, Macmillan, 1987.

[11] KUSUMA, V. A. et al. Crosslinked Poly(ethylene oxide) Containing Siloxanes Fabricated through Thiol-ene Photochemistry, Journal of Polymer Science A Polymer Chemistry, 2015, vol. 53, p. 1548 - 1557.

About Authors... Marina ALBALADEJO SIGUAN was born in February 1993 in Valencia, Spain. In September 2016 she received her Bachelor degree in Electrical Engineering from the RWTH Aachen University, Germany. She is currently studying her Masters in Micro- and Nanotechnology as also working as a research assistant student at the Institute of Materials in Electrical Engineering 1 at RWTH Aachen University.

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Roland FISCHER was born in Dortmund, Germany in 1986. He received his Dipl.-Ing. degree in mechanical engineering from RWTH Aachen University, Germany, 2012 and is now pursuing his doctorate degree at the Institute of Materials in Electrical Engineering 1, RWTH Aachen University, Germany. His research interests include thin, flexible and stretchable CMOS devices, diagnostic sensors for medical applications and other topics in design and fabrication of microsystem devices.