Interfacial Reinitiation of Free Radicals Enables the Regeneration of Broken Polymeric Hydrogel Actuators

Abstract

Open AccessCCS ChemistryRESEARCH ARTICLE10 May 2022Interfacial Reinitiation of Free Radicals Enables the Regeneration of Broken Polymeric Hydrogel Actuators Baoyi Wu, Huanhuan Lu, Yukun Jian, Dachuan Zhang, Yu Peng, Jie Zhuo, Xiaoxia Le, Jiawei Zhang, Patrick Théato and Tao Chen Baoyi Wu Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Huanhuan Lu Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Yukun Jian Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Dachuan Zhang Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 , Yu Peng Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Jie Zhuo Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Xiaoxia Le Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Jiawei Zhang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 , Patrick Théato *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] Soft Matter Synthesis Laboratory, Institute for Biological Interfaces III, Karlsruhe Institute of Technology (KIT), D-76344 Eggenstein-Leopoldshafen Institute for Chemical Technology and Polymer Chemistry, Karlsruhe Institute of Technology (KIT), D-76131 Karlsruhe and Tao Chen *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049 https://doi.org/10.31635/ccschem.022.202201942 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Living organisms, from plants to animals, have inspired and guided the design and fabrication of polymeric hydrogels with biomimetic morphology, shape deformation, and actuation behavior. However, the existing polymeric hydrogels are fragile and vulnerable, which seriously hinders further application. Therefore, endowing hydrogels with a biomimetic self-growth property and regenerating the macroscopic shape of hydrogels after they suffer significant damage are highly desirable for the next generation of adaptive biomimetic hydrogels. Inspired by the tail regeneration of geckos, we herein report an efficient and universal strategy of interfacial diffusion polymerization (IDP), which can regenerate the polymeric layer at a solid–liquid interface, thereby growing new hydrogels on the existing hydrogel layers. Through changing the solvent viscosity and/or monomer type of the hydrogel precursor, diverse new hydrogels have been regenerated to endow the initial hydrogels with additional fluorescent functions and/or actuating properties. Due to the high efficiency and universality of IDP, an injured hydrogel actuator can be repaired, regenerated, and recovered to its initial condition, even after suffering severe damage such as cutting or piercing. We believe that the regeneration strategy of polymeric hydrogels will inspire the design of biomimetic materials and motivate the fabrication of the next generation of soft robots with adaptive and multifunctional properties. Download figure Download PowerPoint Introduction Nature is an unlimited source of inspiration and has guided the design and fabrication of versatile intelligent artificial materials.1–9 Hydrogel actuators,10–12 which are one of the most promising classes of such bionic materials,13,14 can imitate the morphology and deformation of biological organisms due to their wet and soft properties.15–19 However, most of the existing hydrogel actuators are fragile and vulnerable, which seriously hinders the development of hydrogel actuators in complex situations.20–27 As one of the most promising bionic materials, self-healing hydrogels can repair themselves when the damaged parts are close enough to form chemical bonds or noncovalent interactions but can not regenerate a missing part when the hydrogel suffers from huge damage. Besides, the existing self-healing hydrogels usually require that the damage be fresh; otherwise, the self-healing becomes more and more inefficient.28–31 By contrast, although biological organisms also suffer from huge damage, the injured parts can still recover to their initial state via body metabolism. Moreover, biological organisms can also exhibit self-growth properties which are capable of endowing them with brand new functions.32,33 For example, tadpoles only breathe through their gills and swim under water, propelling themselves with their tails. Interestingly, after metamorphosis, tadpoles grow into frogs, who breathe through their lungs and jump with their limbs. Inspired by this growth behavior of biological organisms, the development of next-generation bionic hydrogel actuators with self-growing properties is receiving immense scientific attention.34–36 In order to realize the self-growth and functionalization of the as-prepared hydrogels, the reinitiation of the polymerization and a tough interfacial interaction between original hydrogel and newly generated hydrogel are unavoidable.37–46 Recently, a few strategies have been proposed successfully. For example, Gong and coworkers regenerated mechano-radicals and reinitiated polymerization by force-induced polymer strand scission.37 A double-network hydrogel containing monomer was subjected to repetitive mechanical loading that destroyed the polymer chains and induced the generation of mechano-radicals, which reinitiated the polymerization of the monomer. Further, Daraio and coworkers utilized the photosynthesis of embedded chloroplasts to reproduce glucose inside a hydrogel network and remodel microstructures under white light exposure.38 Also, Zarket and Raghavan proposed an inside-out technique for creating multilayered polymer capsules.39 Although the above-mentioned studies proposed the possibility of linking/reconstructing the hydrogel layers with firm interfacial toughness, the polymerization mechanism and applications were still unclarified, which limited the further development of self-growth hydrogel. Therefore, to propose an efficient and universal techniques for the growth of the macroscopic shape of as-prepared hydrogels remains a challenge. Inspired by the tail regeneration of the gecko that can secrete and transport growth hormone to its injured part and regenerate a new tail by the division of cells in the injured part (Scheme 1a), herein, an efficient strategy is proposed that endows hydrogels with such a self-growing property via an interfacial diffusion polymerization (IDP). Different from other reported methods that reinitiate the polymerization within the hydrogel, free radicals in the IDP strategy were generated via a redox reaction at the solid–liquid interface between ammonium persulphate (APS) in an as-prepared hydrogel and N,N,N′,N′-tetramethylethylenediamine (TEMED) in another hydrogel precursor (Scheme 1b). Here, the initiating polymerization at the solid–liquid interface exhibits several advantages. (1) The new hydrogel could grow on the surface of the initial hydrogel and increase the macroscopic volume of the whole system. (2) The hydrogel precursor could fully moisten the initial hydrogel surface and prevent oxygen from getting in, which commonly acts as a polymerization inhibitor. (3) Polymerization at the solid–liquid interface could enhance the interfacial interaction between two layers, thereby generating a unique interpenetrating network at the interface. (4) This approach represents a universal strategy that can be adapted to generate diverse new hydrogels on hydrogel-based substrates and hydrophilic substrates. (5) Such an IDP strategy could custom repair an injured hydrogel actuator. Different from those self-healing hydrogels that require fresh damage and potential self-healing factors such as supramolecular interaction or dynamic covalent bonds,47,48 any injured hydrogel actuators could be repaired and recover to their initial condition both in macroscopic shape and chemical structure and continue functioning via IDP. We believe this will provide a new vision and inspire the fabrication of the next generation of adaptive robots, multifunctional hydrogel actuators, and biomimetic systems. Scheme 1 | Gecko-inspired regeneration of polymeric hydrogels. (a) The typical regeneration process of severed gecko tails. The injured gecko would secrete and transport growth hormone which induces the division of cells in the injured part and regenerates until the injured part is recovered. (b) Gecko-inspired hydrogel-regenerating strategy. The free radicals were reinitiated at the solid–liquid interface and induced the polymerization in order to reconstruct the new hydrogel network. Download figure Download PowerPoint Experimental Methods Materials Acrylamide (AAm), 2-hydroxyethyl methacrylate (HEMA), 1-pyrenylbutyric acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl), 4-dimethylaminopyridine (DMAP), and sodium chloride (NaCl) were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Allylamine, sodium alginate (Alg), N,N′-methylene bis(acrylamide) (BIS), CH2Cl2, APS, TEMED, calcium chloride (CaCl2), gelatin, polyvinyl alcohol (PVA), ferroferric oxide (Fe3O4), rhodamine B, congo red, methyl violet, methyl blue, tartrazine, xylenol orange sodium salt (XO), ammonium ferrous sulfate (Fe(NH4)2·(SO4)2·6H2O), and ethylene diamine tetraacetic acid (EDTA) were purchased from Aladdin Reagent Co., Ltd. (Shanghai, China). N-hydroxyethyl acrylamide (HEAA), and N-isopropylacrylamide (NIPAm) were purchased from TCI Reagent Co., Ltd. (Shanghai, China). 4-Bromo-1,8-naphthalicanhydrideand, and N,N′-dimethylethylenediamine were bought from Energy Chemical Co., Ltd. (Anhui, China). Instruments The lyophilizing process was conducted in the DGJ-10C freeze dryer (Shanghai Boden Biological Science and Technology Co., Ltd., Shanghai, China). The tensile tests were conducted on the Z1 Zwick/Roell Universal Testing System (Shanghai Zwick Testing Equipment Technical Service Co., Ltd., Shanghai, China). Tensile tests were performed at room temperature with the tensile speed of 10 mm/min. Samples were punched into dumbbell shapes (size: length × width × thickness: 50 mm × 3 mm × 1 mm). The images and videos of hydrogel were taken by a polarizing microscope (OLYMPUS, 71781687-5, Japan). UV–vis absorption spectra were recorded by virtue of TU-1810 UV–vis spectrophotometer provided by Purkinje General Instrument Co., Ltd. (Beijing, China). The patterned hydrogels were obtained by laser cutter (GY-460 bought from Shandong Liaocheng Guangyue Laser Equipment Co., Ltd., Shandong, China). The fabrication of the substrate hydrogel The fabrication of the substrate polyacrylamide hydrogel AAm (0.71 g), Bis (21.3 mg), APS (21.3 mg), TEMED (15 μL), and deionized water (10 mL) were mixed to form an aqueous solution. Then the hydrogel precursor was added into a 1 mm thick mold. The polymerization was carried out at room temperature for 6 h. After polymerization, the polyacrylamide (PAAm) hydrogel was immersed in deionized water to remove unreacted monomer and reach a swelling equilibrium. Fabrication of the substrate PNIPAm hydrogel NIPAm (2 g), Bis (20 mg), APS (20 mg), TEMED (20 μL), and deionized water (10 mL) were mixed to form an aqueous solution. The hydrogel precursor solution was added into a 1 mm thick mold. The polymerization was carried out at 4 °C for 12 h. After polymerization, the PNIPAm hydrogel was immersed in deionized water to remove unreacted monomer and reach a swelling equilibrium. Fabrication of the substrate polyvinyl alcohol hydrogel PVA was dissolved in deionized water (weight ration of PVA to H2O is 1∶9) under an oil bath at 95 °C for 4 h to form an aqueous solution. The solution was added into a 1 mm thick mold. During the freezing/thawing treatment, the PVA solution was frozen under −18 °C for 6 h and thawed at room temperature for 2 h. The procedure was repeated three times in order to get PVA hydrogels. Fabrication of the substrate gelatin hydrogel Gelatin was dissolved in deionized water (the weight ratio of gelatin to H2O was 3∶20) under an oil bath at 60 °C for 1 h to form an aqueous solution. The solution was added into a 1 mm thick mold. The gelatinization process was carried out in a 4 °C environment. Fabrication of the substrate Alg-Ca2+ hydrogel Gelatin (15 g), CaCl2 (1.11 g), and deionized water (100 mL) were mixed to form an aqueous solution at 60 °C in an oil bath, and the gelatin-Ca2+ hydrogel was prepared using a similar procedure to prepare the gelatin hydrogel. Then 2% alginate solution was put on the top of gelatin-Ca2+ hydrogel. After 10 min, the Alg-Ca2+ hydrogel was obtained after transferring the gelatin/alginate hydrogel into warm water to remove the gelatin. The measurement of free radical concentration PAAm hydrogel was selected as the substrate hydrogel in this experiment. The PAAm hydrogel was immersed in 15 mg/mL APS solution overnight. Then the hydrogel was removed, and the surface was dried. The low viscosity precursor was prepared by mixing AAm (0.71 g), Bis (21.3 mg), I2959 (21.3 mg), Fe(NH4)2·(SO4)2·6H2O (0.196 g), and deionized water (10 mL). The high viscosity precursor was prepared by mixing linear polyacrylamide (0.71 g), AAm (0.71 g), Bis (21.3 mg), I2959 (21.3 mg), Fe(NH4)2·(SO4)2·6H2O (0.196 g), and deionized water (10 mL). A PAAm hydrogel sheet (size: length × width × thickness: 40 mm × 10 mm × 1 mm) was first put into a homemade mold including one hollow silicone rubber sheet and two glass side pieces. Then the precursor was injected into the mold on top of the PAAm hydrogel. After 10 min, the hydrogel was irradiated under ultraviolet light (365 nm) for 5 min. The newly generated hydrogel was cut into strips 20 mm × 1 mm × 1 mm. An aqueous solution of 250 μM XO and 20 mM H2SO4 was used to determine the Fe3+ content. After soaking the strips in 4.0 mL XO solution for 10 min, 3 mL solution was then taken from the test tube for UV–vis light analysis to determine the Fe3+ concentration. The observation of interfacial diffusion polymerization PAAm hydrogel was selected as the substrate hydrogel in this experiment. The PAAm hydrogel was immersed in 15 mg/mL APS solution overnight. Then the hydrogel was removed and the surface dried. The precursor was prepared by mixing linear polyacrylamide (0.71 g), AAm (0.71 g), Bis (21.3 mg), TEMED (150 μL), and deionized water (10 mL). A PAAm hydrogel sheet (size: length × width × thickness: 40 mm × 10 mm × 1 mm) was first put into a homemade molding including one hollow silicone rubber sheet and two glass side pieces. The model was placed on the stage of an optical microscope. Then the precursor was injected into the mold, and the generation of the new hydrogel was recorded and measured. The fabrication of hydrogel via interfacial diffusion polymerization Some hydrophilic materials could be selected as the substrate, such as the PAAm hydrogel, gelatin hydrogel, calcium alginate hydrogel (Alg-Ca2+ hydrogel), PVA hydrogel, paper, cloth, skin, fruit peel, and so on. All of the above hydrophilic substrates were immersed in 15 mg/mL APS solution overnight. The precursor was prepared by mixing polymers, monomer (1 M), crosslinking agent (3 wt % of monomer), dye, TEMED (15 μL/mL), and deionized water. For example, precursor 1 was prepared by mixing alginate (0.2 g), AAm (0.71 g), Bis (21.3 mg), TEMED (150 μL), and deionized water (10 mL) to form an aqueous solution. The precursor was coated on the surface of the substrate. After 30 min, a bilayer hydrogel was obtained after washing the ungelatinized precursor with deionized water. A polydimethylsiloxane (PDMS) mold with a cutout pattern was placed on a substrate, and the precursor was placed on the top of the PDMS mold. After 30 min, a patterned hydrogel was obtained after washing the ungelatinized precursor with deionized water. The process of hydrogel custom repair During the fabrication and forthputting process, hydrogel actuator may face various types of damage that may destroy its function and interrupt the task in progress. In order to demonstrate this, various types of injury—such as piercing, cutting, and severing—were endowed to the two-dimensional butterfly-shaped hydrogel actuator. To custom repair the function of the hydrogel actuator, the injured part was treated with 15 mg/mL APS first. Then the hydrogel precursor containing AAm as monomer was utilized to repair the injured part of the bottom layer hydrogel (PAAm) via IDP. Subsequently, the AAm in the hydrogel precursor was replaced with NIPAm to repair the top layer hydrogel (PNIPAm) via IDP. Ultimately, all kinds of injuries were repaired, and the repaired hydrogel actuator was able to continue the incomplete task. Theoretical model In order to describe the dynamic distribution process of free radicals in solution, the convection-diffusion control equation was adopted, and the expression is as follows: ∂ C A ∂ τ + u x ∂ C A ∂ x + u y ∂ C A ∂ y + u z ∂ C A ∂ z = D AB ( ∂ 2 C A ∂ x 2 + ∂ 2 C A ∂ y 2 + ∂ 2 C A ∂ z 2 ) + r A In the above formula, CA represents the concentration of the diffusing substance component A, ux, uy, and uz represent the diffusion speed of the substance, respectively, DAB represents the diffusion coefficient of the diffusing substance A in B, and rA represents the amount of component A generated by chemical reaction in a unit volume of space per unit time. τ represents time, and x, y, and z represent spatial coordinate positions. In this study, CA describes the concentration of the free radical components of the gel, and DAB represents the diffusion coefficient of the gel in the growth solution. Because the chemical reaction is considered, the growth solution is poured on the surface of the acrylamide hydrogel. APS in acrylamide will diffuse from the inside of the gel to the growth solution. APS will react with Fe2+. Therefore, rA is determined by the following chemical reaction equation: Fe 2 + + S 2 O 8 2 − → SO 4 • − + SO 4 2 − + Fe 3 + ⟶ XO ( yellow ) Fe 3 + − XO ( Purple ) The finite element method was processed by Transport of Diluted Species (TDS). The initial parameters were defined as follows: the initial concentration of S2O82− was 15 mg/mL and the initial concentration of Fe2+ in the hydrogel precursor was 100 mM. The definition of the boundary condition parameters: the bottom and two sides were set as closed boundaries (No Flux), and the top boundary was set as an open boundary (Open Boundary). The diffusion coefficient values were set as 3*10−7 m2/s in the viscous solution and 2*10−10 m2/s in the viscous solution (where the viscous growth solution contained 100 mM Fe2+, 20 mM xylenol orange (color indicator), and 1M linear polyacrylamide. The above chemical reaction processes were defined via the Chemistry (chem) module. The reacting substances and the generated substances were in a one-to-one correspondence with the four diffusing substances in the TDS module since the reaction was irreversible. The reaction rate rA parameter, the amount of chemical reaction generated in a unit volume of space per unit time, was jointly determined by the forward rate constant of the reactants Fe2+ and S2O82− and defined by default in the software. Additionally, the Enthalpy of reaction and Entropy of reaction adopted the definition of Automatic. Finally, the reaction rates of each substance were coupled into the TDS module, and they affected the diffusion of the generated substances. Results and Discussion As is well known, the generation of free radicals is the key step in free radical polymerization. Therefore, in order to clarify the mechanism of the polymerization process of IDP, the as-prepared hydrogel was immersed into the solution of initiators (APS), and the initiators diffused into the hydrogel network until they reached equilibrium. Then, a solution containing Fe2+ as a reduction agent and xylenol orange (XO) as indicator of Fe3+ formation was poured onto the surface of the initial hydrogel to monitor the generation and diffusion process of free radicals (Figure 1a). The generation and monitoring process of free radicals can be described as follows. Due to the osmotic pressure at the solid–liquid interface, initiator molecules diffused from the hydrogel network into solution while the Fe2+ diffused from the solution into the hydrogel, which triggered the redox reaction and generated Fe3+ and free radicals. As soon as redox initiation occurred, the Fenton color reaction set in and resulted in a color change from yellow to purple, due to the metal coordination between XO and Fe3+ (Figure 1b). With the ongoing diffusion of APS, Fe2+ ions were further oxidized into Fe3+, and the color of the solution gradually changed from yellow to purple. Figure 1 | monitoring of the diffusion of free radicals. (a) of the generating and diffusing process of free radicals. (b) The absorption spectra of XO and The images and finite element analysis the diffusing process of free radicals in solution. The images and finite element analysis the diffusing process of free radicals in viscous solution. The and of the concentration of free radicals in positions. The the mechanism of regeneration and diffusion of free radicals. 1 Download figure Download PowerPoint the viscosity of the solution was the diffusion rate was and a of unreacted APS from the interface and the generation process of free radicals (Figure and Therefore, to the diffusion rate of APS, polyacrylamide (PAAm) was dissolved into the solution in order to increase the viscosity of the solution. With the viscosity of the solution, the diffusion rate of APS In the generation process of free radicals more and a between and unreacted parts was and forward by the diffusion of APS (Figure and Further, the diffusing process of APS and the generating process of free radicals were by finite element and the are highly with the is that the of free radicals is to that of Fe3+ and the concentration of Fe3+ ions for of the concentration of free radicals. Therefore, the concentration of Fe3+ ions was determined by UV–vis light absorption analysis ( Figure and the concentration of free radicals was As in Figure was an distribution of free radicals when using a solution with the concentration of free radicals was mM in 1 and mM in In contrast, in a viscous solution, the concentration of free radicals to mM in 1 while the concentration of free radicals by two of to mM in With the of finite element the diffusing mechanism was ( Figure In the low viscosity solution, the diffusion of APS in APS at the solid–liquid interface, which induced a low free radical initiation rate on the one more unreacted APS diffused further into the solution, which generated free radicals from the interface on the other However, in the solution with the diffusing process of APS was by the polymer chains inside the solution (Figure Therefore, more APS at the solid–liquid interface, which induced a initiation rate of free radicals due to the high concentration of APS into the solution, in a distribution of free radicals. As the of a solution affected the generation process and diffusion rate of free the polymerization more This to the IDP strategy to the fabrication of hydrogels. Also, in order to the function of the new hydrogel, a hydrogel precursor containing AAm as TEMED as reduction Bis as and alginate as was onto the surface of an hydrogel. As in Figure the initiator diffused from the hydrogel into the solution while AAm and Bis diffused from the solution into the hydrogel network of the osmotic pressure at the solid–liquid interface. a of free radicals was generated via redox initiation with APS and TEMED, which triggered the process of at this Finally, a new hydrogel was and gradually on the top of the initial hydrogel. with the IDP strategy generated free radicals within the solid–liquid interface, so the newly hydrogel network into the initial hydrogel network and an interpenetrating network at the interfacial (Figure the process, optical on the boundary between the part and the which can be as a when with an optical microscope. Therefore, with the of an optical the self-growth process the new hydrogel was in