Leeches Inspired Hydrogel-Elastomer Integration Materials

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Surfaces, Interfaces, and Applications

Leeches Inspired Hydrogel-Elastomer Integration Materials Jun-Feng Feng, Jiao-Long Chen, Kun Guo, Jun-Bo Hou, XianLi Zhou, Shuai Huang, Bang-Jing Li, and Sheng Zhang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b12886 • Publication Date (Web): 14 Sep 2018 Downloaded from http://pubs.acs.org on September 16, 2018

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ACS Applied Materials & Interfaces

Leeches Inspired Hydrogel-Elastomer Integration Materials Jun-Feng Feng †,‡,, Jiao-Long Chen †, Kun Guo †, Jun-Bo Hou §, Xian-Li Zhou ‡, Shuai Huang ‡, * Bang-Jing Li †, *,Sheng Zhang §,* †

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China § State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Sichuan University, Chengdu, 610041, China ‡ School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China KEYWORDS：mimicry, self-healing, micelle cross-linking, tough material, hydrogel-elastomer

ABSTRACT: Inspired by the functions of leeches, for the first time homogeneous materials integrating hydrogels and elastomers was achieved by free radical polymerization. 2-Mehtoxyethyl acryate (MEA) was used as elastomer monomer and Pluronics functionalized with vinyl groups act as cross-linkers to impart the hydrogel property to the materials. The resulting Pluronic/PMEA gels possess a swelling ratio of about 210 % and good water-retaining ability. Compression tests of Pluronic/PMEA gels at swelling equilibrium state show a stress up to 1.6 MPa under 85 % strain. The gels act as elastomer after dehydrated. Uniaxial tensile fracture stress and the elongation reached 1200 kPa and 500 % respectively, and compression stress

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is above 22 MPa. Furthermore, the Pluronic/PMEA gels also show self-healing properties. Due to the excellent mechanical performance in both wet and dry condition, this hydrogel-elastomer integrated materials may have potential applications in tissue engineering, soft robotics and biomedical devices.

INTRODUCTION Soft materials have received significant attention because their widely application in modern technologies including biomedical devices,1-4 tissue engineering,5,6 drug delivery,7 stretchable and bio-integrated devices,8-11 optics12-14 and soft robotics.15,16 It consists of hydrogels and elastomers which all have their own unique characteristics. Hydrogels’ merits including high water contents, various chemical and biological molecules permeability, biocompatible and/or biodegradable; whereas elastomers are mechanically robust and stable in various environments. Since the advantages of hydrogels and elastomers are complementary to each other, it is natural to think about designing a material that integrating the merits of both soft materials. Leeches are a subclass (Hirudinea) of segmented worms (phylum Annelida), it is a creature that shows both the merits of hydrogels and elastomers.17 The flexibility can assure leeches show a elongation up to 5 times of their original length and ingest 3 to 10 times their weight in blood. They can also live under severe dehydration and a wide range of temperature, even a 40 % of water losses against their body weight, they can still survive and show body elasticity.18 Some species of segmented worms even exhibiting capability of regeneration an entire individual from


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a single mid-body segment.19 If a material possessing characters of leeches that will be of great importance in the field of bio-integrated researches. However, in most technological applications, hydrogels and elastomers are used separately,4-16 since the hydrogel-elastomer hybrid always suffered from weak interfacial bonding.20-22 Recently, Zhao and his co-workers developed a kind of hydrogel-elastomer hybrids with robust interfaces by crosslinking and grafting pre-shaped interpenetrated hydrogel on the surface of modified elastomer. This method solved the problems of low robustness, weak interfacial bonding and microstructure patterning of hydrogel-elastomer hybrid,23-25 but still the hybrid is a combination of two different materials. A facile method capable of fabricating a homogeneous and functional material like leeches is still a critical demand and central challenge in the field. Inspired by the functions of leeches, here we report a simple method capable of assembling elastomer monomers with amphiphilic micelles into homogeneous structures with excellent mechanical property in both wet and dry states, water-retaining property and self-healing ability. 2-Mehtoxyethyl acrylate (MEA) was used as elastomer monomer because its hydrophobic nature and low glass transition temperature after polymerized. Different kinds Pluronics were functionalized with vinyl groups act as cross-linkers to impart the hydrogel property to the materials. The current study for the best of our knowledge is the first time not only addresses the long-lasting challenge of developing robust material with the merits of hydrogels and elastomers, but also introducing a new way to integrate hydrogels and elastomers into



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one homogeneous material. Due to the excellent mechanical performance in both wet and dry condition, this hydrogel-elastomer integrated materials may have potential applications in tissue engineering, soft robotics and biomedical devices.

Scheme 1 Schematic illustration of the synthesis of pluronic diacrylate and the corresponding hydrogels, xerogels with micelles as cross-linkers.

RESULTS AND DISCUSSION Preparation of Pluronic/PMEA gels. The general synthesis of Pluronic/PMEA gels are described as follows. First, a series of Pluronics were modified with vinyl groups. Pluronics are typical amphiphilic triblock copolymers (PEOm-PPOn-PEOm) with different molecular weight and associative properties, which self-assemble into micelles easily in aqueous solution.26-29 The micelles with vinyl functional groups replaced traditional chemical cross-linkers co-polymerized with acrylics monomer 2-mehtoxyethyl

acryate

(MEA)

yielding

Pluronic/PMEA

hydrogel.

The

Pluronic/PMEA hydrogel shows good water-retaining ability and mechanical strength.


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After dried, the Pluronic/PMEA xerogel exhibit elastomer properties as shown in Scheme 1. Four selected Pluronics, which have similar PEG content but different molecular weight, were acrylated by reacted them with acryloyl choride in the presence of trimethylamine (the detailed information of Pluronic was showed in Table S1). The acrylation were confirmed by 1H NMR (Figure S1-S4) and FTIR (Figure S5). The acrylation degree of all the selected Pluronics was more than 95% (calculated on the basis of 1H NMR data). The modification of end hydroxyl groups did not affect the hydrophilicity of the PEO blocks, thus the amphiphilic triblock copolymers self-assemble in aqueous solution into micelles easily. Figure 1 showed the size and morphology of typical Pluronic diacrylates micelles (F108DA). As shown in Figure 1a, the critical micelle concentration (CMC) of the Pluronic F108DA was determined by fluorescence study using pyrene as a probe. At low concentration of F108DA, pyrene exhibited relatively low fluorescence intensity because the pyrene was in water and few micelles were present. However, the fluorescence intensity increased remarkably with the increasing of the concentration, this reflected the pyrene was encapsulated in the interior of the micelles. CMC was determined from the crossover point in the low concentration ranges. The CMC of F108DA micelles is 0.6 mg/ml, which was supported by other works.30 Dynamic light scattering (DLS) results showed that the size of F108DA micelles were around 180 nm (Figure 1b). Figure 1c showed transmission electron microscopy (TEM) images of F108DA. It can be seen that these micelles have a size of about 40 nm. The different size distribution between



DLS and TEM is because the shrinkage of micelles during the solvent evaporation process under light heat before TEM tests, also the TEM tests are under vacuum condition which caused the different size distribution. DLS tests the hydrated particle size of the micelles. What’s more, the F108DA triblock has a lower critical solution temperature (LCST), during the evaporation under heat, the hydrophobic interaction of the PPO blocks increases, which causes the decrease of F108DA micelles size.31,32

Figure 1. Characterization of F108DA micelles. a) I373/I384 vs log[F108DA] profile for pyrene at 25 ℃. b) DLS results of F108DA micelles. c) TEM microscopy images of the F127DA micelles.

The Pluronic/PMEA gels were successfully prepared through a one-pot copolymerization of Pluronic diacrylates micelles and 2-methoxyethyl acrylate (MEA), the resulting hydrogels were shown in Figure 2b, the micelles enhanced the solubility of MEA, so the Pluronic/PMEA gels have regular shapes and smooth


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surface. Figure 2a shows the picture of MBAA crosslinked control-gel, because of the hydrophobic nature of MEA monomers, the control-gel showed phase separation during the polymerization, which caused the rough surface and irregular structure of control-gel. Scanning electron microscopy (SEM) was used to further study the inner structure of two different kinds of materials. Figure 2c exhibits the SEM result of control-xerogel, some cracks and small cavities were observed, indicating the nonuniformity of the control-gel. Compared to the control-gel, the F108DA-xerogel showed even texture, without particle aggregation and phase separation. This is because the elastomer nature of PMEA, after dried, the F108DA gel

(Figure 2d).

This special structure of Pluronic/PMEA gels are quite different from the conventional hydrogel, which a pore structure is common in the hydrogel microstructure. Pluronic/PMEA xerogel showed a compact structure, no matter nature dried or freeze dried. We supposed that this interesting phenomenon was due to the elastomer nature and hydrophobic property of PMEA matrix. For their matrixes are hydrophilic. The hydrophilic polymer matrix swelled and contained a lot of water in the network in the wet state. After being dried, the water evaporated and left pore structure. But in the case of the Pluronic/PMEA gel developed by this study, the PMEA matrix was hydrophobic. Hydroscopicity of Pluronic/PMEA attributed to the hydrophilic PEO structure in Pluronic micelles. As a result, the Pluronic/PMEA xerogels showed compact as elastomer, but not conventional hydrogel.



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Figure 2. a) Photo of control-gel. b) Photo of four pluronic/PMEA gels. SEM images of c) control-xerogel and d) F108DA-xerogel.

Swelling property and hygroscopicity of pluronic/PMEA gels. PMEA is a kind of hydrophobic elastomer. As shown in Figure 3a, the swelling ratio of PMEA in water was only around 16 %. However, the swelling ratios of four Pluronic/PMEA hydrogels reached 210 %, indicating that the introduction of Pluronic imporved the hydrophilicity greatly. The swelling ratios of the four hydrogel were similar, suggesting that they had close cross-link densities. After dehydration, all the Pluronic/PMEA

xerogels

show

better

hygroscopicities

compared

to

the

control-xerogel (Figure 3b). Under the humidity of 100 %, the hygroscopicity of four Pluronic/PMEA xerogels showed twice higher than the control-xerogel, also confirming that the hydrophilic PEO structure of Pluronic micelles increased the hydrophilicity of Pluronic/PMEA gels. The different hydrophilicities of four


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Pluronic/PMEA xerogels were related to the molecular weight and PEO block content of Pluronics. F68DA-xerogel, F128DA-xerogel and F108DA-xerogel all have the same PEO block content of 80 %, but with increasing of molecular weight, the PEO units increased, they showed increasing of hygroscopicity especially under high humidity. F127DA-xerogel has a similar hygroscopicity to F68DA-xerogel, although the molecular weight of F127DA is higher than F68DA, the length of PEO segment of both Pluronics are quite close.

Figure 3. a) Swelling ratio of four pluronic/PMEA gels and control-gel. b) Hygroscopicity of pluronic/PMEA gels and control-gel in different humidities.

Water-retaining property and thermodynamic property of pluronic/PMEA gels. The water retaining ability is crucial for leeches and other creatures, the strategy for leeches is the secrete of cuticles that made of collagen fibers to prevent excessive water evaporation, and the hydrophilic proteins inside the body can also help retain water, so the leeches can live even under a 40 % of water losses against their weight. The Pluronic/PMEA gels also show better water retaining property than control-gel because the hydrophilic PEG blocks inside the gel. The as-prepared Pluronic/PMEA hydrogels were weighted (M0) and then put into oven at 40℃, this temperature was



considered only occurs in an extreme climate. The hydrogels were weighted at a specific interval (Mn), and the final xerogel were weighted (Mx), the cumulative water loss = (M0–Mn) / (M0–Mx)×100 %. As shown in Figure 4a, the control gel shows higher water loss than F108DA gel under any time interval. After 7 hours drying, the water losses ratio of control gel reached 80 %, compared to a 40% water losses of F108DA gel. The control gel almost reached a xerogel state after 12 hours heating in oven compared with the F108DA gel possessing a water loss ratio of 62 %. Glass transition temperature (Tg) is an indicator to polymer segment mobility and increases as the chain mobility is hindered,33 if the Tg of a polymer is lower than room temperature, the polymer may show self-healing ability due to the flexible chain movement. Diﬀerential scanning calorimetry (DSC) thermograms showing changes in glass transition temperature for F108DA-gel and control-gel are depicted in Figure 4b. Both F108DA-gel and control-gel have a Tg of about -38℃, indicating the introduce of Pluronic micelles have little effect on the Tg of PMEA gel. Notably, there is a endothermic peak at 45℃ of Pluronic/PMEA gel, which can be explained by the crystallization of PEO block during the drying process.34


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Figure 4. a) Cumulative water loss of F108DA-gel and control-gel. b) DSC thermogram of F108DA-gel and control-gel.

Mechanical property of pluronic/PMEA hydrogels. Leeches show excellent deformation resistance and good elongation behavior, so we also tested the mechanical performance of Pluronic/PMEA gels. The mechanical tests were performed by using Pluronic/PMEA hydrogels at the equilibrium swelling state. Compressive tests at a crosshead speed of 10 % strain per min were showed in Figure 5a.

The

compression

stress

of

F108DA-hydrogel,

F128DA-hydrogel

and

F127DA-hydrogel reached megapascal under the strain of 85 %, and it is twice higher than the control-gel. F68DA-hydrogel failed the compressive test at a fracture strain of 64 %, this is mainly due to the energy dissipation mechanism of Pluronic/PMEA hydrogels is the deformation of Pluronic micelles. F68DA has the lowest molecular weight, so the polymer chain is shorter than three other Pluronics. Under large deformation the smaller micelle cross-linked hydrogels are more likely to form cracks and later broken. Pluronic/PMEA

hydrogels

also

showed

good

elastic

resilience.

F108DA-hydrogel did not fracture at 90 % compressive strain and recovered 95 % to the initial height within 1 min (Figure 5b 1-2). The control-hydrogel started losing water when stress was applied, and can not recover the shape (Figure 5b 3). Cyclic compressive loading-unloading tests on F108DA-hydrogel with 85 % strain with a 2 min stop between each cycle resulted in overlapping hysteresis loops (Figure 5c). In contrast, the loading-unloading loops of control-hydrogel shows a



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dramatic decrease of stress right after the second half of a cycle (Figure 5d). Figure 5e further plots the variation of the compressive stress over time upon cyclic loading-unloading

tests,

which

demonstrates

the

quick

recovery

of

the

F108DA-hydrogel after unloading with negligible decay for four consecutive cycles. These results indicate an excellent fatigue resistance of these Pluronic/PMEA hydrogels. It has been reported that the hydrogel crosslinked by micelles may show tough and elastic since the chain slippage and disentanglements of soft micelles under loading.35 It is noted that the control-hydrogel showed high stress after the first run (Figure 5f), this could be attributed to the loss of water in the first run. After the water loses, the control-gel becomes tougher.

Figure 5. a) Compressive stress-strain curves of pluronic/PMEA hydrogels and control-hydrogel at 85% strain. b) The picture of F108DA-hydrogel at strain of 85% b1), after compressive test b2) and the control-hydrogel after compressive test b3). c)


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Cyclic compressive stress-strain and (e) stress-time curves at 85% strain of F108DA-hydrogel. d) Cyclic compressive stress-strain and f) stress-time curves at 85% strain of control-hydrogel.

Mechanical property of pluronic/PMEA xerogels. Unlike leeches still gain their toughness while losing water, most hydrogels show hard and brittle properties when dehydrated. It is interesting that Pluronic/PMEA hydrogels developed by this study act as elastomers and exhibit even better mechanical strength after losing water. The Pluronic/PMEA xerogels were prepared by drying the hydrogels in the vacuum oven at 60℃ for 24 h. All the Pluronic/PMEA xerogels showed better tensile strength than the control-xerogel upon uniaxial tensile tests at a crosshead speed of 80 mm×min-1 (Figure 6a and 6b). The reason why Pluronic micelles can enhance the mechanical strength of Pluronic/PMEA xerogels can ascribe as follows: first, the self-assemble of hydrophobic PPG chain into core functions as cross-linking point and the hydrophobic force enhance the mechanical strength of Pluronic/PMEA xerogels. What’s more, the crystallization of PEO chain during the drying process also attribute to the increase of mechanical strength of Pluronic/PMEA xerogels. In the case of F68DA-xerogel, F128DA-xerogel and F108DA-xerogel, which all have a PEO content of 80 %, their tensile strength and fracture strain increase along with the increase of molecular weight. F128DA-xerogel has a close molecular weight to F127DA-xerogel, but a higher PEO content, as a result, F128DA-xerogel exhibits a higher tensile strength and lower fracture strain. These results suggested that the crystallization of PEO attributes to the increase of mechanical strength. So no matter



the increase of the PEO content of the molecular chain or the increase of molecular weight cause the increase of whole PEO chain in the system, and then contribute to the enhancement of mechanical strength. The tensile strength of F108DA-xerogel even reached megapascal with a strain of 500 %. On the other hand, the hydrophobic aggregation of PPG chain improved the toughness of Pluronic/PMEA xerogels. When the molecular weight of Pluronics increased, the whole PPG chain in the system increased the mechanical strength and fracture strain of Puronic/PMEA xerogels improved simultaneously. F127DA-xerogel and F128DA-xerogel have similar molecular weight, while the fracture strain of F128DA-xerogel is lower owing to the smaller content of PPG. Because the hydrophobic force is much smaller than covalent bond force, when external force applied to the material, partial of PPG hydrophobic force fractured as sacrifice bond. Cyclic tensile loading-unloading tests at crosshead speed of 80 mm×min-1 were conducted to reveal the energy dissipation mechanism of F108DA-xerogel (Figure 6c). The first loading-unloading cycle exhibited a hysteresis, and this hysteresis loop suggests energy dissipation presumably due to the molecular chain movement of the polymer matrix. The following runs exhibited smaller hysteresis loops, indicating good toughness of the material. The reversibly generate and rupture of the hydrophobic force between the Pluronic PPG chains responsible for the excellent elastic resilience of the material. Compressive tests of these Pluronic/PMEA xerogels at a crosshead speed of 10 % strain per min showed extraordinary strength and toughness. The xerogels did not fracture at 90 % compressive strain, the compressive


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stress at 90 % strain increased along with the molecular weight of Pluronics, the compressive stress of F108DA-xerogel at 90 % strain reached 66.9 MPa (Figure 6d).

Figure 6. a)The tensile stress-strain curves of pluronic/PMEA xerogels and b) the corresponding tensile strength of pluronic/PMEA xerogels. c) Cyclic tensile curves of F108DA-xerogel at 400% strain for four cycles. d) Compressive stress-strain curves of pluronic/PMEA xerogels at 90% strain.

Self-healing properties of pluronic/PMEA xerogels. Despite the good mechanical performance, some species of segmented worms also show self-healing property and even regeneration. The control-PMEA xerogel and Pluronic/PMEA xerogels also show self-healing property to some extent without other treatment or additives. They had a close healing efficiency about 40 % at 5 ℃. The chain



movement of PMEA is supposed to be the main reason to this self-healing behavior. The introduction of micelles did not affect the self-healing properties of materials.

CONCLUSION In summary, we developed a novel and facile strategy to construct a kind of hydrogel-elastomer integration materials. The key structural features of these materials are amphiphilic micellar cross-linkers and elastic matrix. These materials are able to adsorb water as hydrogel and act as elastomer after dehydration. These distinctive materials integrate complementary advantages of both elastomers and hydrogels and may explore many diverse applications.

ASSOCIATED CONTENT

Supporting Information Experimental and information of selected Pluronics; 1H NMR of the synthesized F127DA, F68DA, F128DA, F108DA; FTIR of the synthesized F127DA, F68DA, F128DA, F108DA. These materials are available free of charge via the Internet. AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. *E-mail:[email protected]. *E-mail: [email protected]. Notes


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The authors declare no competing financial interest.

ACKNOWLEDGMENT This work was supported by National Natural Science Foundation of China (Grant Nos. 51573187, 51373174) and State Key Laboratory of Polymer Materials Engineering (Grant sklpme2017-2-05).

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Leeches Inspired Hydrogel-Elastomer Integration Materials

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