Highly Stretchable and Biocompatible Strain Sensors Based on

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Highly Stretchable and Biocompatible Strain Sensors Based on MusselInspired Super-Adhesive Self-Healing Hydrogels for Human Motion Monitoring Xin Jing, Hao-Yang Mi, Yu-Jyun Lin, Eduardo Enriquez, Xiang-Fang Peng, and Lih-Sheng Turng ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b06475 • Publication Date (Web): 04 Jun 2018 Downloaded from http://pubs.acs.org on June 4, 2018

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ACS Applied Materials & Interfaces

Highly Stretchable and Biocompatible Strain Sensors Based on Mussel-Inspired Super-Adhesive Self-Healing Hydrogels for Human Motion Monitoring Xin Jing1,2,3, Hao-Yang Mi1,2,3*, Yu-Jyun Lin2, Eduardo Enriquez2, Xiang-Fang Peng3, and Lih-Sheng Turng1,2* 1

2

Wisconsin Institute for Discovery, University of Wisconsin–Madison, 53715, WI, USA

Department of Mechanical Engineering, University of Wisconsin–Madison, 53706, WI, USA 3

Department of Industrial Equipment and Control Engineering, South China University of Technology, Guangzhou, China

*

Corresponding authors: Lih-Sheng Turng, email: [email protected] Hao-Yang Mi, email: [email protected]

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Abstract Integrating multifunctionality such as adhesiveness, stretchability, and self-healing ability on a single hydrogel has been a challenge and is a highly desired development for various applications including electronic skin, wound dressings, and wearable devices. In this study, a novel hydrogel was synthesized by incorporating polydopamine-coated talc (PDA-talc) nanoflakes into a polyacrylamide (PAM) hydrogel inspired by the natural mussel adhesive mechanism. Dopamine molecules were intercalated into talc and oxidized, which enhanced the dispersion of talc and preserved catechol groups in the hydrogel. The resulting dopamine-talcPAM (DTPAM) hydrogel showed a remarkable stretchability, with over 1000% extension and a recovery rate over 99%. It also displayed strong adhesiveness to various substrates, including human skin, and the adhesion strength surpassed that of commercial double-sided tape and glue sticks, even as the hydrogel dehydrated over time. Moreover, the DTPAM hydrogel could rapidly self-heal and regain its mechanical properties without needing any external stimuli. It showed excellent biocompatibility and improved cell affinity to human fibroblasts compared to the PAM hydrogel. When used as a strain sensor, the DTPAM hydrogel showed high sensitivity, with a gauge factor of 0.693 at 1000% strain, and was capable of monitoring various human motions such as the bending of a finger, knee, or elbow, and taking a deep breath. Therefore, this hydrogel displays favorable attributes and is highly suitable for use in human-friendly biological devices. Key words: Polydopamine (PDA); Hydrogel; Adhesiveness; Self-Healing; Biocompatibility


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1. Introduction Flexible human-friendly devices are of special interest for multifunctional wearable electronic devices1-2, which are currently in high demand. To meet the requirements of complex human motion and safety for direct skin contact, stretchable, recoverable, and biocompatible substrate materials are highly desirable and have been attracting tremendous amounts of attention in recent years3-5. Hydrogel as a crosslinked, water-containing solid has been used in various applications, such as tissue engineering scaffolds6-8, contact lenses9-11, wound dressings12-13, drug delivery14-16, etc. Due to the complexity of their chemical structure, hydrogels have a wide range of macroscopic properties. Recently, several flexible hydrogels, which have properties close to human skin, were developed and assembled into various wearable sensors to monitor human motion by transforming human motion into electrical signals including current, resistance, and capacitance2, 16-17. Although many of these devices showed high sensitivity for signal detection, there is great motivation to integrate more functions into the hydrogel to improve the performance stability and enhance the human experience. Most wearable devices fabricated in recent studies, although they may be flexible, usually lack stretchability and recoverability, which greatly restricts their use for human joint motion18-20. Pursuing highly stretchable and recoverable hydrogels with desired electrical properties is an ongoing task. Cai et al. reported extremely stretchable strain sensors based on a borax-crosslinked polyvinyl alcohol/carbon nanotube composite hydrogel, which could be stretched up to 1000% but showed a large hysteresis resulting from the stretching–releasing cycles21. Self-healing is another desirable attribute for multifunctional hydrogels. With selfhealability, hydrogels can be easily reshaped and reused even when they are partially damaged.



As such, it will greatly reduce the repair and replacement costs for the hydrogel device. Integrating self-healing properties into biosensors would greatly enhance the robustness and service lifetime of the device. Many electronic hydrogels have been developed and have shown good self-healing behavior. For example, by polymerizing pyrrole in agarose solution, Park developed a self-healing conductive hydrogel22. Bao et al. prepared a self-healing electronic sensor based on a supramolecular organic polymer with embedded nickel-nanostructured microparticles23. However, those healable hydrogels had limited stretchability at less than 100%. Therefore, there is a need to combine high stretchability and self-healing abilities to develop hydrogel systems for applications such as robotics, human motion detectors, and medical monitoring and treatment. Almost all wearable devices need to use tape, a belt, or stitches to attach to the human body or clothes5, 24-25. A biocompatible adhesive platform that sticks tightly to human skin and cloth is highly preferred to minimize the device size and enhance the human experience. Recently, inspired by the mussel adhesive mechanism, a number of adhesive hydrogels have been developed26-29. The adhesiveness of the synthesized hydrogels originates from partially oxidized dopamine, which shows high adhesiveness to varied surfaces and good biocompatibility during the self-polymerization process of dopamine30-31. Due to the presence of catechol groups, polydopamine (PDA) has been used in preparing self-healing hydrogels32-34. Han et al. developed a clay-initiated polydopamine–polyacrylamide (PDA–PAM) composite hydrogel that displayed superior toughness due to nano-reinforcement by clay and PDA-induced cooperative interactions26. Moreover, their group also developed a stimuli-free adhesive PDA–PAM hydrogel by preventing the over-oxidation of dopamine; their hydrogel could repeatedly adhere onto and be stripped from various surfaces28. Therefore, this mussel-inspired chemistry opens a pathway


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for integrating adhesiveness to biosensors. In addition, since many wearable sensors are intended for direct contact with human skin, the biocompatibility of the hydrogel becomes a major requirement. PDA has a structural similarity to the adhesive protein of mussels, which displays high adhesiveness to many surfaces and demonstrates excellent cell affinity30-31, 35. The sensitivity of the device is always the first priority for biosensors. Hydrogels are intrinsically conductive due to the large amount of water and the small molecules in the hydrogel. For resistive strain sensors, the change in resistance of the hydrogel upon deformation is the main cause of the signal change. In order to enhance the sensitivity, conductive fillers—such as carbon nanotubes36-38, graphene20,

39-40

, conductive polymer polypyrrole22, and microfluidic

channels41-42—have been introduced to various sensor systems. Liu et al. prepared nanostructured supramolecular conductive elastomers (NSCEs) using rubber latex particle-reinforced carbon nanotube/cellulose nanocrystal/polyethylenimine (CNT/CNC/PEI) composites, which showed similar sensitivity for human motion monitoring even after bending over 10 000 times. However, the prepared strain sensor could only be stretched less than 200% and required a second band-aid to attach it to the human body4. Therefore, it is highly desirable to develop a hydrogel system that integrates stretchability, self-healing, adhesiveness, conductivity, and biocompatibility all at the same time. In light of the highly preferred multifunctional hydrogel, and motivated by the mussel adhesive mechanism, in this study, we aimed to synthesize a novel hydrogel capable of integrating all of the aforementioned special properties. Furthermore, we aimed to specifically investigate its application as a strain sensor for human motion monitoring. We have previously found that adding dopamine into biocompatible chitosan/graphene oxide hydrogels endowed them with excellent self-healing properties and enhanced stretchability43. In this study, it was



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surprisingly found that talc induced the partially oxidation of dopamine, and polydopamine modified talc particles achieved uniform dispersion in the PAM hydrogel, which together led to significantly enhanced mechanical properties and excellent adhesiveness for the hydrogel. The developed dopamine-talc-PAM (DTPAM) hydrogel integrates several desirable features including high stretchability, self-healing property, adhesion ability, biocompatibility, and conductivity, which make it extremely suitable for wearable sensors to detect human motion.

2. Experimental Methods 2.1 Materials Dopamine hydrochloride (DA), talc powder (10 µm), acrylamide (AM), ammonium persulfate

(APS),

N,N’-methylenebisacrylamide

(MBAA),

tetramethylethylenediamine

(TEMED), and potassium chloride (KCl) were purchased from Sigma–Aldrich (Milwaukee, WI, USA). Other chemicals involved in this study were bought from Thermo Fisher Scientific. 2.2 Methods 2.2.1 Preparation of hydrogels Talc powder was added into the DA solution and magnetically stirred at 700 rpm for 8 h at room temperature to achieve the intercalation and oxidation of DA, which was named PDAtalc. Then, the acrylamide (AM) monomer powder and KCl were added to the PDA-talc solution and stirred for 30 min under the protection of nitrogen in an ice bath. After that, N,N’methylenebisacrylamide (MBAA) was added into the solution and stirred for 15 min. Next, ammonium persulfate (APS) and TEMED were added and stirred for 15 min. After that, the ice bath and stirrer were removed. After degassing for 15 min, the solution was casted into a glass


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petri dish and placed in the oven at 60 °C for 4 h to ensure complete gelation. The compositions of the hydrogels are listed in Table S1. 2.2.2 HEF1 cell culture HEF1 fibroblast cells derived from the human embryonic stem cell line WA09 (WiCell Research Institute) were used as the cell model to investigate the cytotoxicity of the hydrogels. The cells were cultured in a cell culture medium composed of 80% knockout Dulbecco’s modified Eagle’s medium (KO-DMEM) (Invitrogen, CA), 20% fetal bovine serum (FBS) (FBS, WiCell), 1% penicillin–streptomycin (10, 000 U/mL, Life Technologies), 1% L-glutamine (200 mM, Life Technologies), and 1% MEM non-essential amino acids (Life Technologies). When the cells reached 70% confluency, they were passaged using Trypsin-EDTA (Life Technologies). Before cell seeding, the prepared hydrogels were immersed into PBS for 24 hours and then washed with fresh PBS three times. Then, the washed hydrogels were sterilized under UV light for 30 min on each side. After sterilization, the hydrogels were placed into 24 well plates and seeded with cells at a density of 105/cm2. Then the cells were cultured in an incubator setting of 5% CO2 and 37°C and fed with HEF1 media every two days. 2.3 Characterizations 2.3.1 General characterizations The FTIR spectra of freeze-dried PAM and DTPAM were recorded using a Bruker Tensor 27 spectrometer in transmittance mode (Thermo Scientific Instrument) in the range of 4000–600 cm-1 with a resolution of 4 cm-1. The UV-Vis spectra of DA in deionized water and DA oxidized by talc were recorded from 800 nm to 200 nm on a UV-Vis spectrophotometer (Cary 500 UV-Vis–NIR spectrophotometer).



The morphologies of the freeze-dried hydrogels were observed via a fully digital scanning electron microscope LEO GEMINI (Zeiss, Germany) at a voltage of 3 kV. Before observation, the surfaces of the dried hydrogels were sputter-coated with a thin gold layer. The morphologies of talc and PDA-talc were characterized via a Tecnai 12 transmission electron microscope (TEM) (FEI, USA) at an accelerating voltage of 120 kV. The samples were prepared by dipping a Farmvar-carbon grid into 1 mg/mL of talc and PDA-talc in deionized water. The chemical compositions of DA and PDA-talc were analyzed via X-ray photoelectron spectroscopy (XPS), which was performed on a photoelectron spectrometer with a focused, monochromatic Kα X-ray source and a monoatomic/cluster ion gun (Thermo Scientific, USA). Overlapping C peaks were curve-fitted into their individual components with XPSPEAK 4.1 software. 2.3.2 Mechanical property tests Hydrogels prepared in petri dishes were cut into 50 mm × 10 mm × 1.5 mm (length × width × thickness) rectangular strips for tensile testing. The two ends of hydrogels were sandwiched by two glass slides exposing 15 cm hydrogel length and clamped by the tensile test machine. For compression tests, the hydrogel solutions were poured into 5 ml syringes to prepare cylindrical hydrogels. The size of the hydrogels used for compression testing was 12.1 mm in diameter and 10 mm in length. Tensile tests were performed at a speed of 100 mm/min on a universal testing machine (Instron 5967, USA) with a 30 kN load cell. Three samples were tested for each group. The compression tests were carried out using the cylindrical hydrogels, which were compressed to 80% strain at a speed of 50 mm/min. Moreover, cyclic loading-unloading tensile and compression tests were also performed to evaluate the shape recovery and elastic properties of the hydrogels by 10 continuously repeated cycles.


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2.3.3 Adhesion properties The adhesive strength of the hydrogels was investigated via a lap shear testing method following a previously reported study with some modifications43. Fresh pig skin (bought from the local grocery store) was cut into 10 mm × 10 mm squares and attached to aluminum plates (10 mm in width and 50 mm in length) via cyanoacrylate glue (the original SUPER GLUE Corp.) bought from Grainger Industrial Supply. Then, a piece of 10 mm × 10 mm hydrogel film was applied to the epidermis of the skin and sandwiched by the other piece of porcine skin. Next, the sample was lap-shear tested to failure at a speed of 10 mm/min on the above-mentioned tensile testing machine. The adhesive strength was calculated from the maximum load over the area of the adhesive overlap27. To further investigate the adhesive strength of the hydrogel on different surfaces, the hydrogels were also sandwiched between different substrates including polyethylene terephthalate (PET film, 0.04 mm in thickness, bought from Amazon), glass slides (75 × 25 mm, FisherbrandTM premium plain glass microscope slides, purchased from Fisher Scientific), wood (1.5 mm in thickness, bought from banggood.com), fabric (Crafty Cuts cotton fabric, obtained from Amazon), and steel (mild steel plate 1.5 mm in thickness, bought from Ebay.com), and then tested following the same method as previously described. Furthermore, the adhesive strength of the hydrogel was compared with a commercial glue stick (Avery Glue SticTM, bought from Amazon) and Scotch double-sided tape (3M, bought from Amazon) over different time periods after adhering to different substrates. All measurements were performed in triplicate. 2.3.4 Self-healing properties The self-healing ability of the hydrogel was quantitatively investigated by tensile–heal– tensile testing and compression–heal–compression testing. For the tensile tests, the hydrogels



were stretched until breaking on a universal tensile machine. Then the crosshead was moved back to let the two broken pieces come into contact. Next, the hydrogel was taken out from the machine and put into a Ziploc storage bag to prevent water evaporation. After the hydrogel was healed for 2 hours, it was stretched again following the same parameters. For the compression test, the cylindrical hydrogels were compressed to 80% strain at a speed of 50 mm/min, then the crosshead was moved back and the hydrogel was cut into two pieces. The hydrogels were allowed to heal for 2 hours with the protection of the Ziploc storage bag, and then the healed hydrogels were compressed again using the same testing parameters. 2.3.5 Cell viability, proliferation, and cytoskeleton tests Cell viability was evaluated using a Live/Dead Viability/Cytotoxicity Kit (Invitrogen, USA) that can simultaneously visualize both live and dead cells. Green fluorescent Calcein-AM was used to target esterase activity within the cytoplasm of living cells, while red fluorescent ethidium homodimer-1 (EthD-1) indicated cell death by penetrating damaged cellular membranes. This assay was performed following the manufacturer’s instructions. After staining, the cells were observed using a laser confocal microscope (LSCM, A1RsiTi-E, Nikon). The ImageJ software was used to count the number of live and dead cells. Six images of each sample were recorded, and the cell viability was calculated based on the obtained cell number. A Cell Titer 96 Aqueous One Solution Cell Proliferation Assay (Promega) was carried out for the cell proliferation test. Prior to the experiment, standard curves were established and confirmed by comparison with hemocytometer readings. After aspirating the media, cells were treated with an 83% media, 17% MTS solution and allowed to incubate for exactly one hour. After incubation, 100 µL of spent media were transferred to a clear 96-well plate. The absorbance of this plate at the 450 nm wavelength was read with a GloMax-Multi+ Multiplate


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Reader (Promega) and the subsequent number of cells was determined by comparison with the established standard curves. Phalloidin–tetramethylrhodamine B isothiocyanate (phalloidin– TMRho, Sigma) staining was used to determine the shape and cytoskeleton organization of the cells. This assay was carried out following the methods of our previous studies44. 2.3.6 Preparation of the strain sensor To investigate the potential of using the hydrogel as a strain sensor, the hydrogel was employed as the conductor and the VHB tape (Very High Bond tape 4905, 3M, bought from Amazon) was used to encapsulate it to prevent water evaporation from the hydrogel. For the stretching tests to detect the resistance change, the sensors were fixed on a self-developed stretching stage to apply the different strains. All of the signals were collected using a versaSTAT-3 two-electrode system (Princeton Applied Research, USA) under a constant current of 10 mA.

3. Results and Discussion 3.1 Design Strategy of the Multifunctional Hydrogel In order to incorporate special functionalities—including stretchability, self-healing, adhesiveness, conductivity, and biocompatibility—into one hydrogel, an ingenious approach and material system were proposed in this study mainly based on mussel-inspired chemistry. The hydrogel synthesis procedure and reaction mechanism were illustrated in Figure 1. First, the dispersion of talc nanoflakes in the dopamine solution yields an alkaline environment with a pH of 7.8. Dopamine was polymerized on the surface of 2D talc nanoflakes to enhance the stability of talc in hydrogel system and achieve a partial oxidation state of dopamine. The intercalation of dopamine molecules into talc flakes facilitated the exfoliation and uniform dispersion of talc



particles. Meanwhile, the talc flakes prevented the over-oxidation of dopamine since the nanospaced talc flakes provided a limited oxygen environment to prevent some catechol groups from oxidation28. Moreover, it has been reported in previous studies that the catechol groups on the PDA can chelate with ions such as Mg and Si through the adjacent hydroxyl groups, which would facilitate the anchoring of the PDA molecules on the talc surfaces45-46. Therefore, the mechanical properties of the hydrogel could be further enhanced. When the acrylamide (AM) monomers were polymerized in situ in the presence of a crosslinker and an initiator, the dopamine-modified talc particles and K+ and Cl- ions were confined in the hydrogel system. In the composite hydrogel, the PDA chains not only enhanced the interactions between talc layers and the polymer network by physical entanglement, but also built a network through chemical crosslinking (Figure 1 (1)). Moreover, the PDA chains intertwined to form recoverable bonds, including π–π stacking and hydrogen bonds, in the PAM network47-48 (Figure 1 (2) and (3)).


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Figure 1. The schematic and fabrication process of the DTPAM hydrogel. (a) DA molecules intercalated into talc layers. (b) AM monomers, crosslinkers, and an initiator were added to form the hydrogel. (1) The PDA chains formed with the presence of talc were linked to the PAM chains via interactions between PDA and the amide groups49 (green stars). (2) π–π stacking of PDA and (3) hydrogen bonds in the hydrogel. 3.2 Characterization of DTPAM Hydrogel To reveal and verify the chemistry behind the integrated multifunctionality of the DTPAM hydrogel, UV-visible spectrometry, FTIR, and XPS were used to characterize the PDAtalc particles and the synthesized DTPAM hydrogels. It is believed that the PDA-talc is the key to the hydrogel’s self-healing and adhesive properties, as well as its significantly improved stretchability47. From the UV-vis spectra (cf. Figure 2 (a)), a new peak was detected at a wavelength of 325 nm, suggesting the formation of dehydro-dopamine as observed in periodatemediated oxidation50-51. Similar behavior was also observed in the APS-induced polymerization of APS in a previous study52. However, the peak was broad and the intensity was low compared to fully oxidized dopamine in the literature30, 53, which indicated that the oxidation process was slow and controllable for the PDA–talc system. The inset images show that the dopamine (DA) solution remained colorless while the PDA-talc solution turned black 8 h later, which is strong evidence that talc induced the oxidation of dopamine to form polydopamine (PDA). The XPS high-resolution C1s curve of PDA-talc (Figure 2 (c)) showed a C–O bond at 286.2 eV and a C=O bond at 288.1 eV, which were assigned to the catechol and quinone groups, respectively. The statistical results (Figure 2 (d)) showed that PDA-talc still had a high ratio of C–O groups, thus indicating that a large amount of catechol groups were preserved. In contrast, the C=O groups were not detected on dopamine, as shown in Figure S1 (a) and Figure 2 (d). XPS



measurements were performed on both the hydrogel surface and the middle section to study the uniformity of chemical composition. No difference was observed from the XPS spectra (Figure S1 (b)), indicating the homogenous properties of the DTPAM hydrogel. FTIR results of the DTPAM (0.75%D, 0.75%T) and PAM hydrogels (Figure 2 (b)) showed very similar curve patterns. The stretching vibrations of the C=O group of amide and CH2 scissoring were located at 1656 cm-1 and 1447 cm-1, respectively54. The bands between 3000–3500 cm-1 corresponded to the stretching vibration of the N–H bond, thus indicating the successful synthesis of PAM. A small peak at 1258 cm-1 was observed on DTPAM that corresponded to the C–N stretching vibrations in the phenyl amines. The presence of this band implied the interaction between the NH2 groups of PAM and the catechol groups of PDA28. The low peak intensity was due to the low concentration of dopamine (0.75%). Proton nuclear magnetic resonance analysis results also indicated the presence of interactions between DA and AM (shown in Figure S2).


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Figure 2. (a) UV-vis spectra of DA and PDA–talc solutions. The insets show digital photos of DA and PDA–talc solutions held at room temperature overnight. (b) FTIR spectra of dried PAM and DTPAM (0.75%D, 0.75T%) hydrogels. (c) High resolution XPS spectra of C1s for dried PDA–talc particles. (d) Statistical results of Gauss-fitted peak compositions of dried DA and PDA–talc particles. Scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to investigate the morphology of talc before and after dopamine intercalation. SEM and TEM images (Figures 3 (a) and (c)) show the aggregated and layered structure of original talc flakes. After dopamine modification, the particle aggregates became smaller and the stacked talc layers become less than the original talc (Figures 3 (b) and (d)), thus indicating the successful intercalation of polydopamine (PDA) into the talc layers. X-ray diffraction (XRD) was also performed on talc and PDA–talc to investigate the intercalation behavior of PDA into the talc



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layers. The d-spacing of the PDA–talc hybrid increased from 0.936 nm to 0.944 nm (Figure S4), which indicated that the PDA had intercalated into the interlayer of talc and resulted in an increased gallery height. The morphology of the freeze-dried hydrogels was also investigated and the results are shown in Figure S3. Pure polyacrylamide (PAM) showed a smooth surface, while DTPAM hydrogel showed microfibril structures. The formation of microfibrils might be ascribed to the interactions between PDA and PAM, because DA can form intermolecular interactions with many polymers and affect the growth of ice crystals during freezing28,

55

.

Moreover, it was found that the number of talc aggregates was greater for hydrogels with low DA concentrations (e.g., DTPAM (0%D, 1%T)) and high talc concentrations (e.g., DTPAM (1%D, 1%T)). Figure S5 shows the digital photos of all 22 prepared hydrogels with different DA and talc contents, from which it can be seen that the dispersion of particles was enhanced with the simultaneous increase of DA and talc concentrations, with DTPAM (0.75%D, 0.75%T) showing the optimal results. Without the addition of talc, DTPAM (1%D, 0%T) was a dark brown viscous solution, indicating the over-oxidation of dopamine. Therefore, the combination and concentration of talc and dopamine together are critical factors for the DTPAM hydrogel system.


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Figure 3. SEM and TEM images of the talc and PDA-talc (DA/talc = 1:1, the talc concentration was 1.8 mg/mL) layers: (a) SEM of talc, (b) SEM of PDA-talc (DA/talc = 1:1, the talc concentration was 1.8 mg/mL), (c) TEM of talc, and (d) TEM of PDA-talc (DA/talc = 1:1, the talc concentration was 1.8 mg/mL) The viscoelastic properties of the hydrogel were investigated and the results are shown in Figure S6. A strain sweep was performed to investigate the stability of the hydrogel and observe the critical point during viscoelastic transition. When the strain reached 230%, the storage modulus curve intersected with the loss modulus curve. As the strain was further increased, the storage modulus became lower than the loss modulus, demonstrating the collapse of the crosslinking network in the hydrogel. As demonstrated in Figure S6, the DTPAM hydrogel displayed elastic solid behavior when the storage modulus (G’) > loss modulus (G”) over the entire



frequency range, and the values of both G’ and G” were higher than that of the pure PAM hydrogel. 3.3 Tensile and Compressive Properties and Recoverability To investigate the effects of the talc and dopamine content on the mechanical properties, and to optimize the performance of the DTPAM hydrogel, a series of hydrogels with different talc and dopamine concentrations were fabricated. Tensile and compression tests were carried out on the hydrogels as shown in Figure 4. The tensile strength of the hydrogels increased with an increase of talc content and decreased with an increase of dopamine content, thus indicating that the talc particles had a reinforcing effect and the dopamine had a lubricating effect. The compressive strength showed the same trend as the tensile strength results. The synergistic effect of dopamine and talc had a profound influence on the mechanical properties of the DTPAM hydrogels. If talc is absent, the solution could not form an elastic hydrogel as shown in Figure S5 since dopamine was over-oxidized by APS, and AM was not sufficiently crosslinked. Likewise, without dopamine, the extension ratio of talc/AM hydrogels was low (< 500%) and decreased significantly with increasing talc content due to the aggregated behavior of talc. Remarkably, by carefully adjusting the concentration of dopamine and talc in the range of 0.5 ~ 0.75%, the DTPAM hydrogels achieved extremely high stretchability with extension ratios over 1500% (Figure 4 (b)). Due to its high stretchability, DTPAM (0.75% D, 0.75% T) hydrogel was chosen as an example to further investigate its cyclical properties (Figures 4 (d) and (e)). It can be seen that the hydrogel showed small hysteresis loss in both cyclic tensile and compression tests, thus indicating low energy loss in repetitive loading and unloading for 10 cycles. The recovery rate calculated from the cyclical tests showed that the hydrogel possessed excellent recoverability with a recovery rate of about 100% (Figure S7). Moreover, to evaluate the recoverability of the


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hydrogels, the hysteresis energy, Young’s modulus, and stress were calculated according to cyclic tensile and cyclic compression tests (Figure S8). It was found that the dissipated energy was only 54% of the total energy (the first cycle). However, for the rest of the loading–unloading cycles, the dissipated energy increased slightly, which indicated that the deformed bonds were restored during the process. This further demonstrated that the DTPAM hydrogel had good recoverability.

Figure 4. (a) Tensile strength, (b) extension ratio in tensile test, and (c) compression strength of DTPAM hydrogels synthesized with different dopamine and talc concentrations. (d) Cyclic tensile test and (e) cyclic compression test on DTPAM (0.75% D, 0.75% T) over 10 cycles. Inset images show the recoverability of a film hydrogel and a cylinder hydrogel when subjected to stretching and compression. 3.4 Reversible Super Adhesiveness



Moreover, the hydrogels showed amazing adhesiveness to various substrates. Porcine skin was first used to investigate the adhesiveness of the DTPAM hydrogel to biological skin. As illustrated in Figure 5 (a), in the adhesiveness test, the hydrogel was sandwiched between two pieces of porcine skin that were glued to two steel plates. Sandwiched samples were stretched parallel until breaking apart. Interestingly, it was found that the adhesive strength of hydrogels increased with an increase of dopamine and talc concentration. The DTPAM (0.75% D, 0.75% T) hydrogel showed the highest adhesive strength of 15.2 kPa (Figure 5 (b)) and was chosen for the remaining tests. As demonstrated in Figure 5 (ci), a small piece of the DTPAM hydrogel easily adhered to both a centrifuge tube filled with water (63.2 g) and to a researcher’s hand. As the hydrogel was pulled off the glass, many visible sticky fibrils (indicated by blue arrows) formed on the hydrogel–glass interface (Figure 5 (cii)), thus indicating strong bonding. When one tried to separate the two glass slides that were stuck together by the hydrogel perpendicularly, the hydrogel stretched greatly and formed large fibrils that were still attached to both glass slides even as the distance between the two glass slides increased ten times (Figure 5 (ciii)). Although sticky fibrils formed during separation, no residual hydrogel remained on the glass surface after the hydrogel was fully detached. The DTPAM hydrogel easily stuck to human skin as well, and no irritation was observed after being peeled off (Figure S9 (a)). Moreover, Figure 5 (d) shows that the DTPAM hydrogel had good adhesion to both hydrophobic (leaf) and hydrophilic (glass) surfaces. A small piece of hydrogel (300 mg) can stick two glass slides tightly together and easily hold 50 g of weight, up to a maximum of 500 g of weight. Figure S9 (b) demonstrates that the DTPAM hydrogel could easily stick an iPhone to a monitor screen. Furthermore, it was found that, unlike other hydrogels that would lose most of their properties when they dried out,


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the DTPAM hydrogel actually showed a dramatic improvement in adhesive strength as the water evaporated. The hydrogel’s adhesiveness was evaluated over time to various substrates including polyethylene terephthalate (PET), glass, wood, cotton, fabric, and stainless steel. As shown in Figure 5 (e), the adhesive strength dramatically increased over time as the hydrogel dried out. The adhesive strength after drying for 17 h was 52 to 272 times higher than fresh hydrogel depending on the test substrate. The DTPAM hydrogel also showed much higher adhesive strength than a commercial glue stick and double-sided tape, as compared in Figure 5 (e). The contact angles and the surface energies of the DTPAM hydrogel and various substrates were measured and calculated to understand the differences in adhesive strengths (Table S2 and Table S3). Among all substrates, the steel plate displayed the highest surface energy, 79 mJ/m2, followed by fabric, wood, and glass. Meanwhile, PET demonstrated the lowest surface energy at 45.5 mJ/m2. However, the DTPAM hydrogel had a high surface energy of 83 mJ/m2, which explained its maximum adhesion strength to steel. As previously reported, the catechol groups formed high-strength and reversible coordination interactions on inorganic surfaces, while the oxidized o-quinone groups were able to adhere to organic surfaces via immediate covalent crosslinking, which resulted in the irreversible and quick curing of catechol-containing adhesives55-57. As a result, DTPAM could adhere to both inorganic and organic surfaces.



Figure 5. (a) Illustration of the adhesion measurements of the hydrogels. (b) Adhesive strength of hydrogels containing different dopamine and talc concentrations. (ci) Demonstration of the strong adhesiveness of the DTPAM(0.75%D, 0.75%T) hydrogel, (cii) the formation of sticky fibrils when being peeled off a glass substrate, and (ciii) two glass slides stuck together by hydrogel being stretched apart. (d) Adhesion of the hydrogel to hydrophobic (leaf) and hydrophilic (glass) materials. (e) The adhesiveness of the hydrogel increased as it is dried on different substrates for a period of 17 hours. The adhesive strength was stronger than a commercial glue stick or double-sided tape. Another important attribute of the DTPAM hydrogel was its highly reversible adhesiveness. As demonstrated in Figure S10 and Movie 1, the hydrogel lost its adhesiveness after being totally wetted with water, but the adhesiveness was easily regained when the excess water on the hydrogel surface was absorbed by filter paper. It has been reported that the catechol groups of PDA resemble a bridge interacted at the interface between PDA and the substrates,


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showing a high binding affinity to diverse nucleophiles58. The partially oxidized dopamine in the DTPAM hydrogel contributed to the adhesion properties. However, when the DTPAM hydrogel surface was wetted with water, the water layer hampered the interactions between PDA and the substrates32, and the DTPAM hydrogel regained its adhesiveness when the water layer dried out. Moreover, the hydrogel was hydrophilic and could form strong hydrophilic interactions with water molecules. This could weaken the interactions between the hydrogel and the substrates59. Similar behaviors have been observed in previous studies as well26, 60. The reversible adhesiveness was quantified as well to evaluate the stability of the adhesiveness. It was found that the hydrogel maintained about the same adhesive strength in 5 cycles of wetting and drying on different substrates including PET, wood, and steel (Figure S11). Moreover, it was found that a piece of dried DTPAM hydrogel could regain its high adhesiveness when rehydrated, even after storing it in the atmosphere for 1 month, thus indicating the high stability of the hydrogel. 3.5 Self-Healing Ability and Deformation-Dependent Conductivity As shown in Figure 6 (a), two pieces of cut hydrogel were brought together and the incision disappeared after 30 min resting at room temperature. The mechanical performances of the original and self-healed hydrogels were also measured to quantitatively evaluate the selfhealing effect. Hydrogels were cut apart and allowed to self-heal at room temperature for 2 h before the compression and tensile tests were repeated. As shown in Figure 6 (d), the compression stress–strain curve of the healed hydrogel almost overlapped that of the original hydrogel, thus indicating no deterioration of its mechanical properties. Figure 6 (e) showed that the healed hydrogel could be stretched to over 800%, which revealed good self-healing attributes for the DTPAM hydrogel. The outstanding self-healing abilities of the hydrogel are attributed to the diverse intermolecular actions in the DTPAM hydrogel, as illustrated in Figure 1. In the



hydrogel, due to the interactions between the catechol groups of PDA and the amide groups of PAM, the PDA chains can be linked to the PAM network, which intertwines to form recoverable π–π stacking and hydrogen bonds. Moreover, the amide groups of the PAM chains also formed a large amount of recoverable hydrogen bonds in the hydrogel. These recoverable bonds, which are linked to the hydrogel network, were able to dissipate energy efficiently by the breakage of the non-covalent bonds. Therefore, crack propagation during deformation was prevented, and the hydrogel was endowed with good self-healing abilities28, 59-60. Although covalent bonds of PAM were broken when cut, these reversible interactions were able to restore the hydrogel network quickly upon contact. In addition, an alternate strain sweep was performed to evaluate the rheological recovery behavior of the hydrogel (Figure S12). When the hydrogel was subjected to a strain of 300%, the loss modulus increased with the storage modulus being lower. This demonstrates that the hydrogel network was broken. However, when the strain returned to 1%, the values of the storage modulus G’ and loss modulus G” almost returned to their original values. Furthermore, the breaking and healing behaviors of the hydrogel network were repeated for three more cycles. This demonstrates that the hydrogel has good self-healing abilities. The DTPAM hydrogel possessed sensitive deformation-dependent conductivity, which was ascribed to the ions (K+, Cl-, Mg2+ ) of the hydrogel. The conductivity was first demonstrated together with the self-healing property. As shown in Figure 6 (b), the hydrogel can light a green LED, thus indicating high conductivity. The LED indicator extinguished when the hydrogel was cut into two pieces. The LED was lit again as soon as the two pieces were brought together without the emitted light being obviously dimmed. Figure 6 (c) and Movie 2 show straindependent resistance of the hydrogel. The LED dimmed significantly when the hydrogel was stretched due to the simultaneous increase of length and decrease of cross-sectional area. The


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LED became bright again when the applied force was released, thus indicating that the stretch and release did not damage the ion pathway in the hydrogel. Besides stretching, the DTPAM hydrogel also responded to compression. After the cylindrical hydrogel being self-healed for 1h (in Figure 6 (b)), it was used to test the resistance change upon compression. As shown in Figure 6 (f), the resistance increased by about 80% when the hydrogel was compressed by a finger, and the signal was relatively stable over multiple compressions. All of these results indicate that the DTPAM hydrogel is extremely suitable for self-healing electronic devices such as electronic skin, wearable electronics, and biosensors.



Figure 6. (a) Optical microscope images of the self-healing process of the DTPAM hydrogel after 30 min. (b) The DTPAM hydrogel instantly regains conductivity when the two pieces are brought together. (c) The resistance of the hydrogel increases when being stretched, which diminishes the brightness of the LED. (d) Compression and (e) tensile test results of the original and self-healed DTPAM hydrogels. (f) The resistance change of the healed DTPAM hydrogel in response to finger compression. 3.6 Performance as Strain Sensor for Human Motion Detection As it was demonstrated above, the DTPAM hydrogel incorporates many favorable properties such as high stretchability and recoverability, strong and reversible adhesiveness, nonstimuli self-healing ability, deformation-dependent resistance. These attributes make it suitable for various applications. In this study, it was proposed that this promising material could be used as a strain sensor for human motion monitoring applications. To evaluate the performance of the hydrogel as a strain sensor, the relative resistance change of the DTPAM hydrogel with an increase in strain was first investigated. From Figure 7, it was found that the relative resistance change increased dramatically with an increase in tensile strain. Amazingly, the hydrogel still showed stable resistance, even when it had been stretched to 1000% strain, where an 800% increase of resistance was achieved. This dramatic increase in resistance was attributed to the narrowing of the hydrogel cross-section which slowed the ions transportation. Moreover, the DTPAM hydrogel was able to recover to its original shape after being released and regained its initial resistance, thus demonstrating high reusability and stability. The relative resistance change versus strain was plotted and fit to the polynomial equation y = Ax2 + Bx + C, where y is the relative resistance change, x is the relative strain, and the factor A


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can be used as an indicator of the sensitivity of the sensor61. The A factor was 0.07 for the DTPAM hydrogel, which was two orders of magnitude higher than for previously reported hydrogels21. The gauge factor is a more commonly used parameter for representing the sensitivity of various sensors. For the DTPAM hydrogel, the gauge factor was 0.125 at 100% strain and it increased to 0.693 at 1000% strain. The gauge factor was higher than reported soft strain sensors based on ionic conduction (0.348 at 700% strain)62 and other piezoresistive strain sensors (0.06 at 200% strain)37. Moreover, the DTPAM hydrogel incorporated many other desirable features as presented above. All of these features add value to this unique DTPAM hydrogel sensor.

Figure 7. Images of the hydrogel being stretched at different strains and the plot of relative resistance change via different strains for the DTPAM hydrogel (inset image). To investigate a real application for the DTPAM hydrogel-based strain sensor, the hydrogel was encapsulated using VHB clear stretchable tape to prevent water evaporation over time. Two cables were led out and connected to a resistance meter to monitor and record the



change of resistance in various human motions. As a demonstration, the strain sensor was directly attached to a human body to detect the bending and stretching in normal human motion, as shown in Figure 8. When the sensor was attached to the index finger, it responded to the finger motion rapidly, and the finger bending angle was reflected by the intensity of the relative resistance peak change (Figure 8 (a)). When the hydrogel was attached to the author’s neck, it was able to sense a deep breath, as indicated by Figure 8 (b). The hydrogel was also used to detect the bending of a knee and elbow. It can be seen from Figures 8 (c) and (d) that the signal was strong and the baseline was stable. Bending of the knee showed a larger relative resistance change than bending of the elbow due to the larger strain. Furthermore, some references reported a shifting baseline during the monitoring process because of the hysteresis in shape recovery62-63. Noticeably, no obvious shifting of the baseline was found for this DTPAM hydrogel sensor, which can be attributed to its excellent recoverability. Moreover, to further verify its signal repeatability, the hydrogel sensor was attached to a mechanical length gauge and stretched under the same strain as well as under different strains. The signal change was recorded via the aforementioned method. The results are shown in Figure S13 and movie 3. It was found that the obtained signal was very consistent and repeatable. All of these results demonstrate that the DTPAM hydrogel sensor developed in this study has great potential for use in biocompatible devices for the accurate sensing of human motion.


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Figure 8. Demonstration of real-time human motion detection using the DTPAM hydrogel strain sensor directly attached to a human body. (a) Signal detected for the rapid bending and straightening of a human index finger. (b) Signal detected for a human’s deep breath. (c) Signal detected for the rapid bending and straightening of a human knee. (d) Signal detected for the rapid bending and straightening of a human elbow. 3.7 Biocompatibility Evaluation with Human Fibroblasts Biocompatibility is an important requirement for direct-contact wearable biosensors and devices. As a new material, the synthesized DTPAM hydrogel was used as a biological substrate to culture HEF1 fibroblasts to investigate cytotoxicity and cellular–substrate interactions. Cells were cultured for 10 days, and the cell morphology and proliferation were investigated at day 3 and day 10 time points. Figure 9 (a) shows that cells cultured on the DTPAM hydrogel showed a more spread morphology with clearly visible elongated filopodia compared to cells on the PAM hydrogel, and both hydrogels outperformed the control group at day 3. After 10 days of culture,



the cells had multiplied rapidly to form a great cell colony, demonstrating a flourishing living state on the DTPAM hydrogel. In contrast, cells on the PAM hydrogel and control substrate (a non-treated tissue culture polystyrene plate) showed globular shapes and the cell populations were much smaller than those on the composite hydrogel according to the MTS proliferation data (Figure 9 (c)). It is believed that the dramatic improvement in cell affinity of the DTPAM hydrogel was mainly attributable to the presence of dopamine, since it has been widely confirmed that a polydopamine coating is favorable for the attachment and proliferation of many types of cells due to serum absorption on the surface64-65. Moreover, the live/dead assay results indicated that the DTPAM hydrogel maintained more than 95% cell viability at day 3 and day 10, which was higher than the PAM hydrogel and the control group (Figure 9 (b)). The fluorescence images (Figure S14) showed an obviously larger cell area and stronger fluorescence on the DTPAM hydrogel compared to the PAM hydrogel and the control group. Therefore, these results demonstrate that the DTPAM hydrogel possessed good biocompatibility to human fibroblasts and hence should be a safe candidate material for biomedical and wearable devices. DTPAM also has the potential to be used as a platform for any implantable biomedical applications, such as tissue engineering, in vivo sensing, and implantable actuators.


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Figure 9. HEF1 fibroblast cell culture results. (a) Fluorescence images of the cytoskeleton of cells cultured on the PAM and DTPAM hydrogels and the control culture plate. (b) Statistical results of cell viability from live/dead assays. (c) Statistical results of cell proliferation from MTS assays.

4. Conclusion In this study, a multifunctional hydrogel integrated with high stretchability and recoverability, strong and reversible adhesiveness, non-stimuli self-healing properties, strain-dependent



conductivity, and excellent biocompatibility to human fibroblasts was developed via a facile method by introducing partially oxidized dopamine-coated talc nanoflakes into a traditional PAM hydrogel and using an ionic solution as the solvent. A systematic study of the hydrogel formula, as well as morphological and chemical analyses, revealed that talc was able to induce partially oxidation of dopamine, thus preserving abundant catechol groups on the resulting dopamine-coated talc. It was found that specific dopamine and talc concentrations were required to realize all of these special properties. Over or insufficient oxidation deteriorated the properties of the hydrogel. With optimized dopamine and talc concentrations (e.g., both were 0.75% of PAM), the DTPAM hydrogel showed a simultaneous increase in tensile strength and extension ratio, which were 2.1 and 2.6 times that of the PAM hydrogel, respectively. In particular, DTPAM could be stretched to a strain of over 1000% and still showed excellent recoverability. More importantly, the DTPAM hydrogel showed strong adhesiveness to various substrates, including biological skin. In addition, the hydrogel lost its adhesiveness when the surface was wet, and regained the same adhesion strength when the surface dried. The hydrogel could rapidly self-heal without needing any external stimuli and showed sensitive straindependent resistance. It also showed the high gauge factors of 0.125 at 100% strain and 0.693 at 1000% strain. When assembled into a strain sensor, the hydrogel was able to accurately detect various human motions such as the bending of a finger, knee, and elbow, and even a deep breath. Furthermore, the HEF1 human fibroblast culture revealed excellent biocompatibility with the DTPAM hydrogel, which was attributed to the interactive sites provided by the dopamine. Overall, this mussel adhesive-inspired multifunctional DTPAM hydrogel incorporated almost all of the favorable attributes for human affinitive biomaterials, which can be used as a platform for


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developing various products and devices. As an example, its promising performance as a sensitive strain sensor for human motion monitoring was demonstrated.

5. Acknowledgements The authors would like to acknowledge the financial support of the Kuo K. and Cindy F. Wang Professorship, the Vice Chancellor for Research and Graduate Education (VCRGE) Office, the College of Engineering, and the Wisconsin Institute for Discovery at the University of Wisconsin–Madison, the National Natural Science Foundation of China (21604026; 51603075; 51573063), the Fundamental Research Funds for the Central Universities (2017BQ069; 2015ZM093), the Guangdong Natural Science Foundation (S2013020013855), the Guangdong Science and Technology Planning Project (2014B010104004 and 2013B090600126), and the Guangzhou Science and Technology Planning Project (201604010013).

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Highly Stretchable and Biocompatible Strain Sensors Based on

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