ARTICLE

Fatigue-resistant adhesion of hydrogelsJi Liu 1,2,7, Shaoting Lin2,7, Xinyue Liu2,7, Zhao Qin3,4,7, Yueying Yang2,5, Jianfeng Zang 5✉ &

Xuanhe Zhao 2,6✉

The adhesion of soft connective tissues (tendons, ligaments, and cartilages) on bones in

many animals can maintain high toughness (∽800 J m−2) over millions of cycles of

mechanical loads. Such fatigue-resistant adhesion has not been achieved between synthetic

hydrogels and engineering materials, but is highly desirable for diverse applications such as

artificial cartilages and tendons, robust antifouling coatings, and hydrogel robots. Inspired by

the nanostructured interfaces between tendons/ligaments/cartilages and bones, we report

that bonding ordered nanocrystalline domains of synthetic hydrogels on engineering mate-

rials can give a fatigue-resistant adhesion with an interfacial fatigue threshold of 800 J m−2,

because the fatigue-crack propagation at the interface requires a higher energy to fracture

the ordered nanostructures than amorphous polymer chains. Our method enables fatigue-

resistant hydrogel coatings on diverse engineering materials with complex geometries. We

further demonstrate that the fatigue-resistant hydrogel coatings exhibit low friction and low

wear against natural cartilages.

https://doi.org/10.1038/s41467-020-14871-3 OPEN

1 Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, China. 2 Department of MechanicalEngineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 3 Department of Civil and Environmental Engineering, Syracuse University,Syracuse, NY 13244, USA. 4 Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA. 5 School of Optical and Electronic Informationand Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China. 6 Department of Civil andEnvironmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 7These authors contributed equally: Ji Liu, Shaoting Lin,Xinyue Liu, Zhao Qin. ✉email: zhaox@mit.edu; jfzang@hust.edu.cn

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Tough adhesions between hydrogels and engineeringmaterials have been achieved by covalently anchoringpolymer chains of tough hydrogels on solid surfaces

(Supplementary Fig. 1a)1. When the hydrogel is peeled from thesolid under a single cycle of the mechanical load, the energyrequired for fracturing anchored polymer chains and the energydissipated in deforming the bulk hydrogel synergistically give aninterfacial toughness over 1000 J m−2. However, such toughhydrogel adhesion suffers from fatigue failure over multiple cyclesof mechanical loads, in which the effect of bulk dissipation hasbeen depleted (Supplementary Fig. 1b). The resultant interfacialfatigue threshold (i.e., the minimal fracture energy at whichinterfacial crack propagation occurs under cyclic loads) is equal tothe energy for fracturing a single layer of bonded amorphouspolymer chains, on the order of 1–100 J m−2 2–7.

In nature, the adhesions of tendons, ligaments, and cartilagesto bones are commonly achieved through a transitional interface(Fig. 1a), from the uncalcified collagen nanofibrils (i) to the cal-cified collagen nanofibrils (ii) to the bones (iii) (Fig. 1b)8. At theinterface (ii), nanostructured composites of aligned collagennanofibrils and ordered hydroxyapatite nanocrystals8–13 areanchored on the bones, leading to fatigue-resistant adhesions oftendons, ligaments, and cartilages to the bones (Fig. 1b)12. Forexample, the cartilage–bone interface in the human knee joint cansustain compressive stresses of 1 MPa along with an interfacialtoughness around 800 J m−2 over 1 million cycles of loading peryear14–16.

Here, we propose a bioinspired strategy to achieve fatigue-resistant adhesions of synthetic hydrogels by anchoring orderednanostructures (e.g., nanocrystalline domains) on engineeringmaterials, since the ordered nanostructures require a much higher

energy for fatigue-crack propagation than the correspondingamorphous polymer chains (Fig. 1c). To test this strategy, wechoose poly(vinyl alcohol) (PVA) hydrogels as a model materialsystem, which can readily form nanostructures (e.g., nanocrys-talline domains and nanofibrils) with tuneable crystallinity. Theanchorage of nanocrystalline domains on solid substrates throughdry-annealing treatment gives a remarkable fatigue-resistantadhesion between hydrogels and substrates, with an interfacialfatigue threshold of 800 J m−2. The fatigue-resistant hydrogeladhesion can potentially enable a number of applications such asrobust hydrogel coatings on devices made of various materialsand with various sizes and shapes. In particular, we demonstratethat the fatigue-resistant hydrogel coatings exhibit low frictionand low wear against natural cartilages.

ResultsMechanical characterization of fatigue-resistant hydrogel adhe-sion. We first form the PVA hydrogels with low crystallinity ondiverse solid substrates including glass, ceramics, titanium, alumi-num, stainless steel, polyurethane (PU), and polydimethylsiloxane(PDMS) through a freeze–thawing process7. Then, we dry andanneal the samples to substantially increase the crystallinity withinthe hydrogels (see Methods for details)7, 17. The dry-annealingprocess also induces the formation of hydrogen bonds between theordered nanocrystalline domains and the solid surfaces (Fig. 1d)18.As control samples, we fabricate tough hydrogel adhesion (e.g.,polyacrylamide (PAAm)–alginate hydrogel) and common hydrogeladhesion (e.g., PAAm hydrogel and polyacrylic acid (PAA)hydrogel) to solid substrates by covalently anchoring the polymernetworks of hydrogels on the substrates (see Methods for details)1.

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Fig. 1 Bioinspired design of fatigue-resistant hydrogel adhesion. a Schematic illustration of the fatigue-resistant adhesions between soft connectivetissues (cartilage, tendon, and ligament) and bones. b The transitional interface from uncalcified collagen nanofibrils (i) to calcified nanofibers (ii) to thebone (iii). The nanostructured composites of aligned collagen nanofibrils and ordered hydroxyapatite nanocrystals contribute to the fatigue-resistantadhesions of the cartilages, tendons, and ligaments to the bones. c Bioinspired fatigue-resistant adhesion of synthetic hydrogels by anchoring ordered high-energy nanostructures (e.g., nanocrystalline domains) on engineering materials. These high-energy nanostructures (e.g., nanocrystalline domains) caneffectively pin the crack propagation both at the interface and within the bulk hydrogels, since they require a much higher energy for fatigue-crackpropagation than the corresponding amorphous polymer chains. d Fatigue-resistant adhesion of poly(vinyl alcohol) (PVA) hydrogel to substrates throughthe anchorage of ordered nanocrystalline domains on the substrates with hydrogen bonds.

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Next, we carry out the standard 90° peeling tests on theadhered hydrogel samples under a single cycle and multiple cyclesof loads to measure the interfacial toughness Γ (Fig. 2a) andinterfacial fatigue threshold Γ0 (Fig. 2c), respectively. From asingle-cycle peeling test, the interfacial toughness is measured as

Γ ¼ Fs=W; ð1Þwhere Fs is the steady-state peeling force and W is the width ofthe hydrogel sample (Fig. 2a)19. In a multiple-cycle peeling test,we apply the cyclic peeling force with an amplitude of Fa (Fa < Fs)over N cycles, and measure the interfacial crack extension c as afunction of cycle number N. Accordingly, the applied energyrelease rate G can be calculated as

G ¼ Fa=W; ð2Þ

and the interfacial crack propagation rate as dc/dN. The multiple-cycle peeling test is performed at varied amplitudes of appliedforces to give a plot of dc/dN versus G (Fig. 2c). By linearlyextrapolating the plot of dc/dN versus G to intercept the G-axis,we can obtain the interfacial fatigue threshold Γ0, measured underthis condition20 (Fig. 2d). Notably, the hydrogel samples areimmersed in an aqueous bath and maintain their swollen statethroughout the peeling tests to prevent dehydration. In addition,a thin and rigid nylon film is attached to the surface of thehydrogel sample as a backing to prevent its elongation along the

peeling direction (see Methods for the details on the peelingtests).

As shown in Fig. 2b, while the measured interfacialtoughnesses for both tough hydrogel adhesion (PAAm-alginatewith 1500 J m−2) and fatigue-resistant hydrogel adhesion (PVAwith 7500 J m−2, Fig. 2, Supplementary Fig. 2, and Supplemen-tary Movie 1) on glass are high, their interfacial fatiguethresholds are dramatically different. The interfacial fatiguethreshold of tough hydrogel adhesion (PAAm-alginate) is as lowas 68 J m−2 (Fig. 2d and Supplementary Fig. 3), similar to that ofcommon hydrogel adhesion (9 J m−2 for PAA and 32 J m−2 forPAAm, Supplementary Figs. 4 and 5; Table 1), and comparablewith the energy required for fracturing a layer of amorphouspolymer chains (1–100 J m−2)2–4. By contrast, the fatiguethreshold of fatigue-resistant hydrogel adhesion is 800 J m−2 inboth deionized water (Fig. 2d and Supplementary Fig. 6) andphosphate-buffered saline (Supplementary Figs. 7 and 8),approximating the value for tendon-to-bone adhesion14–16. Tofurther validate the high interfacial fatigue threshold, we apply anenergy release rate of 800 J m−2 on the fatigue-resistant hydrogeladhesion over 30,000 cycles, and observe no interfacial crackpropagation using a camera with a resolution of 20 μm per pixel.This result means that the speed of any possible crackpropagation should be lower than 0.6 nm/cycle, consistent withthe previous validation of fatigue thresholds for hydrogels17

(Fig. 2f, Supplementary Fig. 9, and Supplementary Movie 2). On

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Fig. 2 Mechanical characterization of fatigue-resistant hydrogel adhesion. a Schematic illustration of measuring nominal peeling force F versusdisplacement curve during a single cycle of loading within a water bath. b Representative curves of the peeling force per width of the hydrogel (F/W)versus displacement for the tough hydrogel adhesion (i.e., PAAm-alginate) and fatigue-resistant hydrogel adhesion (i.e., PVA) on a glass substrate.c Schematic illustration of measuring the interfacial crack extension c versus cycle number N during a cyclic peeling test at a peeling force of Fa. d Plot ofcrack extension rate (dc/dN) versus applied energy release rate G= Fa/W for the tough hydrogel adhesion and fatigue-resistant hydrogel adhesion on aglass substrate. The linear extrapolation to the G-axis gives the fatigue threshold Γ0. e Images of interfacial crack propagation during a cyclic peeling testfor tough hydrogel adhesion with a thickness around 3mm (swollen state) at an energy release rate of 200 J m−2, showing substantial interfacial crackpropagation within 5000 cycles. f Images of interfacial crack propagation during a cyclic peeling test for fatigue-resistant hydrogel adhesion with athickness around 100 μm (swollen state) at an energy release rate of 800 J m−2, showing no interfacial crack propagation within 30,000 cycles.g Summary of measured interfacial toughness and interfacial fatigue threshold for fatigue-resistant hydrogel adhesion on various substrates, includingglass, ceramic, titanium (Ti), aluminum (Al), stainless steel, PU, and PDMS. Error bars= standard deviation (n= 3). Scale bars: 10 mm in (e, f).

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the contrary, when the tough hydrogel adhesion is subjected toan energy release rate of 200 J m−2 over 5000 cycles, substantialpropagation of the interfacial cohesive crack can be identified(Fig. 2e).

Furthermore, when the applied energy release rate is higherthan the interfacial fatigue threshold, the interfacial fatigue cracksin both cases (i.e., PAAm-alginate and PVA) may gradually tiltinto the bulk hydrogel and induce fatigue fracture of the bulkhydrogel (Fig. 2e and Supplementary Fig. 10). This failure modeindicates that the interfacial fatigue thresholds of hydrogeladhesion also depend on the intrinsic fracture toughness of thebulk hydrogel, due to possible crack tilting and cohesive failure ofthe bulk hydrogel. The high density of nanocrystalline domainsin the bulk PVA hydrogel gives it a high intrinsic fracturetoughness (i.e., 1000 J m−2)17 and guarantees its high interfacialfatigue threshold (i.e., 800 J m−2). Moreover, the fatigue-resistanthydrogel adhesion exhibits long-term stability with consistentinterfacial toughness and interfacial fatigue threshold aftersoaking in deionized water for 90 days (Supplementary Fig. 11).

In addition to glass, the fatigue-resistant hydrogel adhesion isalso applicable to diverse solid substrates (Fig. 2g and Supple-mentary Fig. 12), including ceramics (Γ0= 470 J m−2), titanium(225 J m−2), aluminum (370 J m−2), stainless W (330 J m−2), PU(420 J m−2), and PDMS (150 J m−2). Their interfacial fatiguethresholds are orders of magnitude higher than that of thecorresponding tough hydrogel adhesion (Supplementary Figs. 13and 14).

Mechanism for fatigue-resistant hydrogel adhesion. Tounderstand the mechanism for fatigue-resistant hydrogel adhe-sion, we vary the annealing time for the PVA hydrogels on glasssubstrates, and then measure the interfacial fatigue thresholdsand characterize the nanocrystalline domains in the hydrogels.The hydrogel without annealing easily detaches from the sub-strates upon hydration. However, by increasing the annealingtime from 0 to 90 min, the interfacial fatigue threshold of thehydrogel adhesion is greatly enhanced from 0 to 800 J m−2

(Supplementary Fig. 15). Correspondingly, the prolongedannealing time (from 0 to 90 min) leads to the significantlyincreased crystallinity (from 12.1 to 33.7 wt% at the swollen

state) and reduced water content (from 67 to 37 wt%) in thePVA hydrogels (Supplementary Fig. 16). In addition, althoughthe freeze–thawing process is crucial for nanocrystal nucleationin hydrogels, varying the freeze–thawing cycles of PVA hydro-gels does not change the adhesion performance significantly(Supplementary Fig. 17), since the subsequent dry-annealingprocess increases the crystallinity much more dramatically thanthe freeze–thawing process17.

We further carry out two-dimensional (2D) grazing-incidencewide-angle X-ray scattering (GIWAXS) measurements on thePVA samples adhered to glass substrates before and afterannealing (100 °C, 90 min). Before annealing, the 2D pattern ofGIWAXS (Fig. 3c, e) exhibits a uniform scattering ring withequal intensity at all different azimuthal angles (θ), suggestingrandom orientation of the nanocrystalline domains (Fig. 3a)21.By contrast, an arc-like scattering feature prominently appearsin the 2D pattern of GIWAXS for samples after annealing, wherethe intense scattering is dominantly aligned along the normaldirection of the hydrogel–solid interface (Fig. 3d, f). This patternimplies that the preferred orientation of nanocrystalline domainsis parallel to the interface in annealed PVA hydrogel samples(Fig. 3b)22. The densely packed and oriented nanocrystallinedomains at the interface can collectively and effectively pin thecrack propagation on the hydrogel–solid interface.

To quantify the effect of forming nanocrystalline domains onthe interfacial fatigue threshold, we carry out all-atom moleculardynamics (MD) simulations to compare the energies required topull out a PVA polymer chain (30 nm in contour length) from ananocrystalline domain and to fracture an amorphous PVApolymer chain of the same contour length (see SupplementaryFig. 18 and Methods for detailed MD setup). It is shown in Fig. 4aand Supplementary Movie 3 that the PVA polymer chain is pulledout from the nanocrystalline domain in a stick-slip manner,because of the dynamic rupture and reforming of massivehydrogen bonds23. Despite the weak strength of a single hydrogenbond, multiple hydrogen bonds within a nanocrystal cooperativelysustain a maximal pull-out force of 6 nN (Fig. 4d, PVA–PVA),slightly higher than the force to fracture the amorphous PVAchain (5.8 nN, Fig. 4c, f, PVA). In addition, the pull-out processrequires a displacement of ~30 nm (i.e., the contour length of thePVA chain), but the fracture process only requires a displacement

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Fig. 3 Mechanisms for fatigue-resistant hydrogel adhesion from experiments. a, b Schematic illustration of the nanocrystalline structures of fatigue-resistant hydrogel adhesion before (a) and after (b) annealing (100 °C, 90min). c, d GIWAXS patterns of fatigue-resistant hydrogel adhesion before (c)and after annealing (d). e, f GIWAXS scattering profiles at azimuthal angles of 10°, 30°, 60°, and 80° for PVA hydrogel before (e) and after (f) annealing.

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of ~3.2 nm (i.e., ~10% of the contour length). Therefore, thecooperative rupture of hydrogen bonds demands a much higherstrain energy (~50,000 kJ mol−1) to pull out the PVA chain thanthat to fracture an amorphous PVA chain with the same contourlength (~6000 kJ mol−1). Moreover, pulling out of a PVA chainbetween the nanocrystal–glass interface requires a higher energy(~70,000 kJ mol−1, Fig. 4b, e, g, PVA–SiO2) than that out of astandalone nanocrystal (~50,000 kJ mol−1), which is consistentwith our observation that the bulk hydrogel fractures during thepeeling test, other than interfacial detachment (SupplementaryMovie 1 and Supplementary Fig. 10). Therefore, introducingnanocrystalline domains on the interface and within the bulkhydrogel synergistically ensures a hydrogel–solid interface withextremely high fatigue resistance.

Potential applications of fatigue-resistant hydrogel adhesion.Materials and devices with complex shapes can be exposed torepeated mechanical loads, which pose a challenge to theircoating materials in terms of fabrication method and long-termrobustness. We demonstrate that the fatigue-resistant hydrogeladhesion can potentially provide a facile and versatile solutiontowards this challenge. We first present a set of materials anddevices, including a glass optical fiber (Fig. 5a before and Fig. 5bafter coating), a glass tube (Fig. 5c, d), a stainless steel spring(Fig. 5e, f), a leaf-shaped elastomer (Fig. 5g, h), and a ball-and-socket metallic joint (Fig. 5i-l), which are coated with a hydrogellayer through a dip-coating, freeze–thawing, and dry-annealingprocess (see Methods for details). The thin (~20 μm in thickness,insets in Fig. 5b, d) and uniform hydrogel coatings are applicableto devices with various feature sizes (from 200 μm in Fig. 5a to

35 mm in Fig. 5i), curvatures (convex surface in Fig. 5a, e, i,concave surface in Fig. 5k, and inner and outer surfaces in Fig. 5c)and diverse materials (glass in Fig. 5a, c, stainless steel in Fig. 5e, i,k, and silicone elastomer in Fig. 5g).

Next, we adopt the ball-on-flat sliding test (ASTM G133,Supplementary Fig. 19a) to evaluate the adhesion, friction, andwear performances of our fatigue-resistant hydrogel coating on astainless steel surface over cyclic mechanical loadings24. ThePAAm–alginate hydrogel coating and the corresponding barestainless steel are selected as control samples for comparison. Asshown in Fig. 6a, b, a constant normal compression load (100 N)is applied on a chicken tibia cartilage (compressive stress of~1MPa), beneath which the sample for the sliding test undergoesreciprocating motion. Within 90 cycles, cohesive fracture occursin the chemically anchored PAAm–alginate hydrogel coating(Fig. 6a and Supplementary Movie 4). On the contrary, thefatigue-resistant hydrogel coating remains mechanically robustand adheres on the substrate over 5000 cycles of reciprocatingmotion (Fig. 6b and Supplementary Movie 5).

We further measure the dynamic friction coefficients betweencartilages and various samples under different compression forcesand different cycles (Fig. 6c, d). In the first cycle, the measuredfriction coefficients for the fatigue-resistant hydrogel coating,PAAm–alginate hydrogel coating, and bare stainless steel surfaceare 0.006, 0.04, and 0.045, respectively. When the cycle number ofthe reciprocating motion reaches 90 (under a compression forceof 20 N), the PAAm–alginate hydrogel coating fails as discussedabove. As the cycle number increases from 1 to 200 (under acompression force of 100 N), the friction coefficient of thefatigue-resistant hydrogel coating increases from 0.006 to 0.02and maintains around 0.02 until the end of the test (5000 cycles,

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Fig. 4 Mechanism for fatigue-resistant hydrogel adhesion from simulations. a An image sequence of pulling out a PVA polymer chain (30 nm in counterlength) from a nanocrystalline domain (PVA–PVA) at different applied displacements d using molecular dynamics simulation. b An image sequence ofpulling a PVA polymer chain (30 nm in counter length) from a nanocrystal-substrate interface (PVA–PVA) at different applied displacements d. Silica isused as a substrate. c An image sequence of pulling an amorphous PVA polymer chain (30 nm in counter length) (PVA) at different applied displacementsd till fracture. d–f Force versus applied displacement for pulling out a PVA polymer chain from a nanocrystalline domain (PVA–PVA, d) pulling out a PVApolymer chain from a nanocrystal–substrate interface (PVA–SiO2, e), and pulling an amorphous PVA polymer chain till fracture (PVA, f). The lighter linesfor the simulation results with force–displacement recorded every 200 fs and the solid lines for the moving average result with a window size of 20 ps anda pulling speed of 0.01 Å ps−1. g Strain energies versus applied displacement for pulling out a PVA polymer chain from a nanocrystalline domain(PVA–PVA), pulling out a PVA polymer chain from a nanocrystal–substrate interface (PVA–SiO2), and pulling an amorphous PVA polymer chain tillfracture (PVA).

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Fig. 6d and Supplementary Fig. 20). Moreover, the frictioncoefficient of the bare metal surface increases from 0.045 to 0.3 asthe cycle number increases from 1 to 300 (under a compressionforce of 100 N), and remain constant afterwards (Fig. 6d andSupplementary Fig. 20).

In addition, the abrasive wear properties on the cartilagesagainst the fatigue-resistant hydrogel coating and the barestainless steel surface after 5000 cycles of the reciprocatingmotion are compared in Supplementary Fig. 21. It is evident thatthe wear on the cartilage against the stainless steel surface is moresevere than that against the fatigue-resistant hydrogel coating,which is consistent with the lower friction coefficient of thefatigue-resistant hydrogel coating. Furthermore, we do notobserve significant wear on the surface of the fatigue-resistanthydrogel coating after 5000 cycles of the reciprocating motionusing both confocal microscopy and scanning electron micro-scopy (Supplementary Fig. 22).

DiscussionInspired by the adhesion between bones and tendons/ligaments/cartilages in the human body, we develop a facile yet generalstrategy for the fatigue-resistant adhesion of hydrogels on diverseengineering materials through bonding ordered nanostructures inthe hydrogels on the engineering materials. This hydrogel–solidadhesion achieves an interfacial fatigue threshold up to 800 J m−2,and enables applications such as long-lasting hydrogel coatings ondevices with various feature sizes, curvatures, and substratematerials. In particular, as a hydrogel coating on metallic sub-strates, the fatigue-resistant hydrogel adhesion exhibits low frictionand low wear under cyclic friction tests. As a versatile strategy forthe design of fatigue-resistant soft-hard interfaces, it is applicableto a wide range of hydrogel materials (e.g., nanofibrillar hydrogels

and nanocomposite hydrogels) and solid substrates (e.g., metals,ceramics, and elastomers). The reported strategy for achievingfatigue-resistant adhesion of synthetic hydrogels to various engi-neering materials makes a number of future research directionsand applications possible by providing a soft cushion between rigidmachines and human body. For example, as a mechanically andbiologically compatible interface, the fatigue-resistant hydrogelcoating on machines can not only transmit electrical, optical,acoustic, chemical and mechanical signals between tissues andexternal devices (e.g., electrodes, optical fibers, ultrasound trans-ducers, prosthetics, and robots), but also show robust perfor-mances over the long term.

MethodsMaterials. For fatigue-resistant hydrogel adhesion, PVA powders (Mw 146–186kDa, 99+% hydrolyzed; Sigma-Aldrich 363065) were used. For tough hydrogeladhesion, acrylamide (AAm; Sigma-Aldrich A8887) was used as the monomer, N,N’-methylenebisacrylamide (MBAA; Sigma-Aldrich 146072) as cross-linker,ammonium persulphate (APS; Sigma-Aldrich A3678) as thermal initiator and N,N, N’, N’-tetramethylethylenediamine (TEMED; Sigma-Aldrich T9281) as cross-linking accelerator, and alginate (Sigma-Aldrich A2033) ionically cross-linked withcalcium sulfate (Sigma- Aldrich C3771) as the dissipative polymer network. AAmand acrylic acid (AA; Sigma-Aldrich 147230) were used as monomers for two typesof brittle hydrogel adhesion. The functional silane solution containing 500 mL ofdeionized water, 50 μL of acetic acid (Sigma-Aldrich 27225), and 2 mL of 3-(tri-methoxysilyl) propyl methacrylate (TMSPMA; Sigma-Aldrich 440159) was usedfor chemical modification of substrates before forming tough hydrogel adhesion.Food dyes (red, green, and blue, McCormick) and fluorescein sodium salt (Sigma-Aldrich F6377) were added in the hydrogels for visualization and fluorescentlabeling, respectively. Dulbecco’s phosphate-buffered saline (DPBS; Gibco) andwater were used as media for peeling test.

Borosilicate glass (McMaster Carr, 8476K36), nonporous glass mica ceramic(McMaster Carr, 8489K232), titanium (McMaster Carr, 9039K15), anodizedaluminum (McMaster Carr, 89015K181), stainless steel (McMaster Carr,8983K115), PDMS (Dow Corning, Sylgard 184), Ecoflex (Smooth-On, 00-10), andPU (Smooth-On, Smooth-Cast 300) were adopted as various solid substrates for

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Fig. 5 Fatigue-resistant hydrogel coatings on various materials with complex geometries. a, b A glass optical fiber (200 μm in diameter) with (b) andwithout (a) fatigue-resistant hydrogel coatings. Inset in b confocal laser-scanning microscopic (CLSM) image of the hydrogel coating (∽20 μm inthickness) on the glass optical fiber. c, d A glass tube with (d) and without (c) fatigue-resistant hydrogel coatings on the inner and outer surfaces. Inset in d3D CLSM image of the hydrogel coating on both inner and outer surfaces. e, f A stainless steel spring with (f) and without (e) fatigue-resistant hydrogelcoatings. g, h A leaf-shaped elastomer with (h) and without (g) fatigue-resistant hydrogel coatings. i, j A convex end of the ball-and-socket metallic jointwith (j) and without (i) fatigue-resistant hydrogel. k, l A concave end of the ball-and-socket metallic joint with (l) and without (k) fatigue-resistanthydrogel coatings. The hydrogel coatings are colorized with fluorescein sodium salt dye for visualization and all the images of b, d, f, h, j, l are taken under ablue light excitation (480 nm in wavelength). Scar bars: 20mm in (a–l), 500 μm in the inset of (b), and 2mm in the inset of (d).

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hydrogel adhesion. A nylon film (100 µm in thickness; TISCH, RS10133) was usedas a stiff backing for the hydrogel samples in the peeling test. Glass optical fiber(200 μm in diameter, with coating and cladding layer removed; Thorlabs,FG200UEA), borosilicate glass tube (McMaster Carr, 8729K66), corrosion-resistantcompression spring (McMaster Carr, 9663K88), stainless steel mortar pestle(Bekith, demo as metallic convex shape), stainless steel measuring spoon head(Amazon, demo as metallic convex shape) were used for the dip coating.

The simulated synovial fluid was prepared following the recipe in the previousliterature25. 0.5 wt% hyaluronic acid (HA,Mw 750–1000 kDa; Sigma-Aldrich, 9067-32-7), 0.01 wt% L-α-dipalmitoyl phosphatidylcholine (DPPC; Sigma-Aldrich, 200-567-6) as liposomes, 1.4 wt% albumin (Sigma-Aldrich, 232-936-2), and 0.7 wt%γ-globulin (Sigma-Aldrich, 232-706-1) as protein additives were dissolved in DPBS.

Fatigue-resistant hydrogel adhesion to various substrates. 10 g of PVA pow-ders were dispersed in 90mL deionized water, and dissolved at 100 °C for 5 h,followed by defoaming with a centrifugal mixer (AR-100, Thinky). All the substrates(i.e., glass, ceramic, titanium, aluminum, stainless steel, PDMS, and PU) werethoroughly cleaned with ethanol and deionized water, and then completely driedwith nitrogen flow. For the stainless steel substrates, they were first polished toremove the surface oxidation layer prior to the cleaning. Cleaned substrates werethen treated by oxygen plasma (30W at a pressure of 200mTorr, Harrick PlasmaPDC-001) for 5 min. Immediately after the plasma treatment, the PVA solution waspoured onto the substrate within an acrylic spacer (Plexiglass, 45 mm× 20mm×1.5mm), fully covered with an acrylic plate (Plexiglass, 75 mm× 50mm× 1.5 mm),frozen at −20 °C for 8 h, and thawed at 25 °C for 3 h. Multiple cycles offreeze–thawing (cycle number= 1 – 5) could be done, but unless otherwise speci-fied, we only performed one freeze–thawing cycle. Then, the acrylic cover andspacer were removed, and the freeze–thawed hydrogels were air-dried on thesubstrate for 8 h and then annealed at 100 °C for 90min to obtain the fatigue-resistant adhesion between PVA hydrogels and substrates. The annealing timewas varied when investigating the effect of annealing time on the PVA hydrogeladhesion (Supplementary Fig. 15). The Young’s modulus of PVA hydrogelsincreases from 200 kPa to 10MPa as the annealing time increases from 0 to90min17. All PVA hydrogels adhered to diverse substrates were immersed inwater to reach the swollen state before testing.

Tough hydrogel adhesion to various substrates. The tough hydrogel adhesion tovarious substrates was fabricated following the previous protocol1. Briefly, thesurface of substrates (i.e., glass, ceramics, titanium, aluminum, and stainless steel)

was functionalized with TMSPMA by incubating the substrates in the functionalsilane solution for 2 h at room temperature. Substrates were washed with ethanoland completely dried with nitrogen flow. The PAAm–alginate tough hydrogeladhesion was fabricated by mixing a carefully degassed aqueous precursor solution(12 wt% AAm, 2 wt% sodium alginate, 0.023 wt% MBAA, and 0.043 wt% APS)with calcium sulfate slurry (0.27 wt% in the mixture) and TEMED (0.1 wt% in themixture). The mixture was poured onto the TMSPMA-functionalized substratewithin an acrylic frame (Plexiglass, 45 mm × 20 mm × 1.5 mm), covered with aglass slide (75 mm × 25mm × 1mm), and incubated at 50 °C for 1 h to achievetough hydrogel adhesion. The Young’s modulus of the tough hydrogel is 40 kPa26.The tough hydrogels adhered to diverse substrates were immersed in water to reachthe swollen state before testing.

Brittle hydrogel adhesion to glass. Following the same surface functionaliza-tion as tough hydrogel adhesion, PAA precursor solution (20 wt% AA, 0.023 wt%MBAA, and 0.043 wt% APS) and PAAm precursor solution (20 wt% AAm, 0.023wt% MBAA, 0.043 wt% APS, and 0.1 wt% TEMED) were poured onto theTMSPMA-functionalized substrate within an acrylic frame (Plexiglass, 45 mm ×20 mm × 1.5 mm), covered with a glass slide (75 mm × 25mm × 1mm), andincubated at 50 °C for 1 h to achieve hydrogel adhesion. The brittle hydrogeladhesions were immersed in water to reach the swollen state before testing.

Measurement of interfacial toughness and interfacial fatigue threshold. Theinterfacial toughness of various hydrogel adhesions was measured using thestandard 90° peeling test (ASTM D2861) with a mechanical testing machine (2 kNload cell; Zwick/Roell Z2.5) and 90° peeling fixture (TestResources, G50). As a rigidbacking during peeling, a nylon film was bonded on the top of hydrogel withsuperglue (Loctite, 1405419). All 90° peeling tests were performed on swollenhydrogels immersed in a deionized water bath or DPBS at a constant loading speedof 120 mmmin−1. The interfacial toughness was measured as Γ= Fs/W, where Fs isthe steady-state peeling force and W is the width of the hydrogel sample19.

To quantify the interfacial fatigue threshold of the hydrogel adhesion to varioussubstrates, we further performed the 90° peeling test under cyclic loading (forcecontrol mode) using the same experiment setup as the standard 90° peeling test. Ina multiple-cycle peeling test, we applied the cyclic peeling force with an amplitudeof Fa (Fa < Fs) over N cycles, and the interfacial crack extension c were recordedfrom the testing machine as a function of cycle number N. Accordingly, the appliedenergy release rate was calculated as G= Fa/W, and the interfacial crackpropagation rate as dc/dN. The multiple-cycle peeling test was performed at varied

N = 5000

Fatigue-resistant hydrogel coating

b

a

0 40 80 1200

2.5

5

7.5

Fric

tiona

l for

ce (

N)

Compression force (N )

0F

rictio

n co

effic

ient

1000 2000

Cycle number

0 3000 4000 5000

0.1

0.2

0.3

c

d

N = 90

Cohesive fracture

Tough hydrogel coating

0.4

Bare metal

Fatigue-resistant hydrogel coating

Tough hydrogel coating

Bare metal

Fatigue-resistant hydrogel coating

Tough hydrogel coating

Fig. 6 Fatigue-resistant hydrogel coating on a stainless steel substrate and sliding against natural cartilages. a Image of tough hydrogel coating onstainless steel plate against cartilage, showing cohesive fracture at the 90th cycle of reciprocating sliding (compression force of 100 N). b Image of fatigue-resistant hydrogel coating on stainless steel plate against cartilage, showing robust adhesion after 5000 cycles of reciprocating sliding (compression forceof 100 N). c Frictional force versus normal compression force for various substrates against cartilages at the first cycle of reciprocating sliding (N= 1).d Evolution of friction coefficient over 5000 cycles of reciprocating sliding for various substrates against cartilages with a normal compression force of100 N (compressive stress of ∽1 MPa) for bare metal and fatigue-resistant hydrogel coating, or a normal compression force of 20 N (compressive stress of∽0.2MPa) for tough hydrogel coating. Error bars= standard deviation (n= 3). Scale bars: 10mm in (a, b).

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applied force amplitudes to give a plot of dc/dN versus G. By linearly extrapolatingthe plot of dc/dN versus G to the x-intercept, we obtained the interfacial fatiguethreshold Γ0, measured under this condition20.

Fatigue-resistant hydrogel coatings. The devices, including glass optical fiber,glass tube, stainless steel spring, Ecoflex elastomer, and ball-and-socket metallicjoints, were cleaned with ethanol and deionized water, dried with nitrogen flow,and treated by oxygen plasma for 5 min. Immediately after the plasma treatment,the devices were dipped in the 10 wt% PVA solution and hung in a sealed containerat room temperature and relative humidity of 90% for 1 h to drain excess PVAsolution. The subsequent freeze–thawing, dry-annealing, and swelling were con-ducted following the above-mentioned procedure.

To visualize the PVA hydrogel coating on diverse substrates and shapes, 0.01 wt% of fluorescein sodium salt for fluorescent labeling was added into the PVAsolution prior to dip-coating. The obtained PVA hydrogel-coated substrates wererinsed with deionized water to remove excess dye solution from the surface beforeimaging. Macroscopic images were taken by a digital camera (D7000, Nikon) underblue light excitation at 480 nm. The hydrogel coating was also imaged using anupright confocal laser-scanning microscope (CLSM; Leica TCS SP8), where thelaser intensity, filter sensitivity, and grayscale threshold were adjusted in eachapplication to optimize the contrast of images. A z-stack acquisition program(~20 µm in slice thickness, 50 steps) was used for 3D scanning, and 3Dreconstruction images were created using the LAS X 3D visualization software.

Friction test. We adopted the ball-on-flat sliding test (ASTM G133)24, which hadalso been used to evaluate the wear property of hydrogel coatings27. Fresh chickentibia cartilages were purchased from a local butcher shop. All procedures wereconducted in accordance with protocols approved by the Massachusetts Institute ofTechnology Committee on Animal Care. A constant normal compression load wasapplied on a chicken tibia cartilage, beneath which a substrate underwent a reci-procating sliding motion. Substrates included bare stainless steel, PVA hydrogeladhered to stainless steel, tough hydrogel adhered to stainless steel. The surface ofeach substrate was sprayed with a thin layer of simulated synovial fluid as alubricant to mimic the working environment of knee joints. We also installedbearings beneath the substrate to reduce friction from the supporting structure(Supplementary Fig. 19). The normal compression load that applied on the chickentibia cartilage by a mechanical testing machine (Zwick/Roell Z2.5) was 5, 20, 25, 45,80, and 100 N. The velocity of reciprocating sliding was set at 5 mm s−1, and theamplitude of sliding distance as 10 mm. We recorded the frictional force betweenthe substrate and cartilage continuously through a force logger (NUL-211, NeulogSensors). The friction coefficients were calculated by dividing the averaged fric-tional force by the normal compression load.

Wear test. Following the same procedure of friction test, we applied the normalcompression load of 100 N on a chicken tibia cartilage, while the substrateunderwent the reciprocating sliding motion for 5000 cycles. The compressive stressbetween cartilage and substrate was ~1MPa, similar to the compressive stress inhuman knee joint27. Once the 5000-cycle test was completed, the cartilage wassoaked in DPBS for 10 min prior to imaging with a digital camera (D7000, Nikon).Slices of cartilage in contact area were sampled and stained with fluorescein forfurther confocal laser-scanning microscopy. For the 3D scanning, z-stack acqui-sition program (~500 µm in slice thickness, 100 steps) was used, and a 3Dreconstruction image was created using the LAS X 3D visualization software. Thesurface morphology of hydrogel coating before and after cyclic loads was imagedvia a scanning electron microscope (JEOL 6010LA).

Grazing-incidence wide-angle X-ray scattering (GIWAXS) measurement.Samples for GIWAXS measurements were prepared by spin-coating (3000 rpm,45 s) of a PVA solution (10 wt%) on a clean glass slide (1 cm × 1 cm),freeze–thawing of the thin hydrogel layer in a humidified chamber and dry-annealing, resulting in a dry film of PVA (~300 nm in thickness) on a glass sub-strate for GIWAXS measurement. On the other hand, a PVA dry film on a glasssubstrate without annealing, and a PVA dry film annealed on a polytetra-fluoroethylene substrate were used as controls (Supplementary Figs. 23 and 24).GIWAXS patterns of the PVA samples were obtained with a Pilatus3R 300Kdetector (Bruker Nanostar), at a radiation wavelength of 1.157 Å and bandwidth of1.5%. The angle of incidence was kept constant at ~0.2°, while the reflection angle2θ was scanned from 3 to 90° in angular steps of 0.1°.

Molecular modeling. MD simulation of PVA crystal and its deformation undermechanical loading force were simulated by using the modified CHARMM27 forcefield implemented by using CHARMM General Force (CGFF) field for PVA modeland a formerly developed force field for silica–water interface28. All the parameters forthe modeling of PVA by CGFF yield the highest penalty of 0.2, which is significantlylower than 10 and strongly indicates the modeling is correct29. We also validated thegeometry of PVA by using discrete Fourier transform calculation with the 6–31G basisset and geometric optimization with the conjugate gradient method and found goodagreement with the current force field. This modified force field enables the calculationof a PVA–water–silica hybrid system. We ran MD simulation with NAMD package

v2.1330. Our nanocrystal model starts from a structure with fully extended chains inparallel with 4.1 Å distance, in analogy to the parallel beta-sheet structures in pro-teins23. It is noted that this conformation (Fig. 4a; Supplementary Fig. 18) agrees withthe former experimental characterization for the spatial distribution of hydroxylgroups31. We added a solvent box around the PVA structure with TIP3P water modelcovering at least 10 Å from the protein structure. The net charge of the system is zeroby adding NaCl of the overall concentration of 0.1mol L−1 and adjust the ratio of ionsto neutralize the system.

MD simulation. All the nanocrystalline structures were equilibrated in an NPTensemble at constant temperature (300 K) and constant pressure (1 atmosphere)controlled by Langevin thermostat and barostat. The simulation time step is 2 fswith rigid bonds model for all the covalent bonds between hydrogen atoms andother heavy atoms. We used particle mesh Ewald function with a grid width <1 Åto calculate the electronic interaction because and it is an efficient method toaccurately include all the long-distance electrostatics interactions. A cutoff lengthof 10 Å was applied to the van der Waals interactions and to switch the electrostaticforces from short-range to long-range forces. We followed the following protocol toequilibrate the structure: (1) energy minimization (10,000 conjugate gradientsteps); (2) equilibration runs for 20 ns (NPT ensemble), where the temperaturestays at 300 K. The carbon atoms of the unit at the right end of the middle PVAchain were pulled by using steered MDs, while the carbon atoms of the units at theother end of the rest chains were fixed. The pulling force was recorded versus theposition. The simulations were carried out at pulling velocities of 0.01 Å ps−1 untilthe chain was fully pulled out from the nanocrystal.

For the pulling test of a single chain until the rupture of covalent bonds, wefixed the carbon atoms at the left end of the chain and pulled the carbon atoms atthe right end at the same speed of 0.01 Å ps−1. It is noted that the CHARMM forcefield does not include rupture of covalent bonds and we thus used first-principlesbased ReaxFF force field32 to evaluate the mechanical behavior of the PVA chainuntil failure.

Reporting summary. Further information on research design is available inthe Nature Research Reporting Summary linked to this article.

Data availabilityThe data that support the findings of this study are available from the correspondingauthor upon request.

Received: 19 June 2019; Accepted: 3 February 2020;

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AcknowledgementsThe authors thank Prof. M. Spector at Brigham and Women’s Hospital for insightfuldiscussions. The work was supported by the Centers for Mechanical EngineeringResearch and Education at MIT and SUSTech (MechERE Centers at MIT and SUSTech).

Author contributionsX.Z., J.L., X.L. and S.L. conceived the idea. J.L., S.L. and X.L. designed the research. J.L.,S.L., X.L., Y.Y. and J.Z. carried out the experiments. Z.Q. performed the moleculardynamics simulation. J.L., S.L., X.L., Z.Q. and X.Z. analyzed and interpreted the results.J.L., X.L., S.L. and X.Z. drafted the manuscript and all authors contributed to the writingof the manuscript. X.Z. and J.Z. supervised the research.

Competing interestsThe authors declare no competing interests.

Additional informationSupplementary information is available for this paper at https://doi.org/10.1038/s41467-020-14871-3.

Correspondence and requests for materials should be addressed to J.Z. or X.Z.

Peer review information Nature Communications thanks Kenneth Shull and the otheranonymous reviewer(s) for their contribution to the peer review of this work.

Reprints and permission information is available at http://www.nature.com/reprints

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Open Access This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,

adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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1

Supplementary Information for

Fatigue-resistant adhesion of hydrogels

Liu et al.

2

Supplementary Note 1

Measurement of water content and crystallinities. The water content within the PVA

hydrogels was quantified following the previous protocol1. Specifically, the swollen hydrogel

samples scratched from the substrates weighing mswollen were incubated at 37 °C for 2 h and

weighed m after air-drying. The mass of the residual water in the as-prepared dry

samples mresidual was measured in the previous section. Therefore, the water content in the

swollen state can be calculated as (mswollen − m + mresidual)/mswollen, and the polymer content in

the swollen state can be calculated as (m − mresidual)/mswollen.

We measured the crystallinities of the resultant PVA hydrogels by differential scanning

calorimetry (DSC/cell: RCS1-3277, cooling system: DSC1-0107), following the experimental

protocols in our previous report2. PVA hydrogel adhered to the substrates were carefully

scratch off with a razor blade, and dried at 37 °C for 2 h.

In a typical DSC measurement, we first weighed the total mass of the air-dried sample

m (still with residual water). The sample was thereafter placed in a Tzero pan and heated up

from 50 °C to 250 °C at the rate of 20 °C min-1 under a nitrogen atmosphere with a flow rate

of 30 mL/min. The curve of heat flow shows a broad peak from 60 °C to 180 °C, indicating

that the air-dried sample contained a small amount of residual water. The integration of the

endothermic transition ranging from 60 °C to 180 °C gives the enthalpy for evaporation of the

residual water per unit mass of the dry sample (with residual water) Hresidual. Therefore, the

mass of the residual water mresidual can be calculated as 0/residual residual waterm m H H , where

0 2260J/gwaterH is the latent heat of water evaporation. The curve of heat flow shows another

narrow peak ranging from 200 °C to 250 °C corresponding to the melting temperature of the

crystalline domains. The integration of the endothermic transition ranging from 200 °C to

250 °C gives the enthalpy for melting the crystalline domains per unit mass of the dry sample

(with residual water) crystallineH . Therefore, the mass of the crystalline domains crystallinem can be

3

calculated as 0/crystalline crystalline crystallinem m H H , where 0 138.6 J/gcrystallineH is the enthalpy of

fusion of 100 wt.% crystalline PVA measured at the equilibrium melting point 0mT 3. Therefore,

the crystallinity in the ideally dry sample dryX (without residual water) can be calculated as

/dry crystalline residualX m m m . With measured water content, the crystallinity in the swollen

state can be calculated as 1swollen dry waterX X .

4

Supplementary Table 1. Summary of various hydrogel adhesions on glass.

Hydrogel Interfacial

toughness (J m-2) Interfacial fatigue threshold (J m-2)

PAA 300 9 PAAm 150 32

PAAm-alginate 1500 68 PVA (90-min annealing) 7000 800

5

Supplementary Figures

Supplementary Figure 1. Failure modes in existing tough hydrogel adhesion. a, Schematic

illustration of the failure modes in tough hydrogel adhesion during a single cycle of loading:

(a-i) adhesive failure by detaching the chemically-anchored amorphous chains from the

substrates and (a-ii) cohesive failure by fracturing the amorphous chains, accompanied with

substantial energy dissipation within the bulk hydrogel. b, Schematic illustration of the fatigue-

induced failure modes in tough hydrogel adhesion under multiple cycles of loading: (b-i)

adhesive failure by detaching the amorphous chains from the substrates and (b-ii) cohesive

failure by fracturing the amorphous chains, with all energy dissipation depleted in both fatigue-

induced failure modes. The resistance to fatigue crack propagation after prolonged cycles of

loading in tough hydrogel adhesion is the energy required to fracture a single layer of polymer

chains (i.e., intrinsic fracture energy of the hydrogel), which is unaffected by the additional

dissipation mechanisms.

6

Supplementary Figure 2. Interfacial toughness of fatigue-resistant hydrogel adhesion on

diverse substrates. Peeling curves for the fatigue-resistant hydrogel adhesion on diverse solids,

including glass, ceramics, stainless steel, aluminium, titanium, PDMS and PU. A peeling rate

of 120 mm min-2 was used.

7

Supplementary Figure 3. Measurement of interfacial fatigue threshold of tough hydrogel

adhesion to glass. Measured crack extension per cycle at applied energy release rates of a. 191

J m-2, b. 145 J m-2, c. 96 J m-2, d. 71 J m-2 and e. 32 J m-2. f. Measured crack extension per

cycle (dc/dN) versus applied energy release rate G. The interfacial fatigue threshold of tough

hydrogel adhesion (i.e., PAAm-alginate) on glass is measured to be 68 J m-2 by linearly

extrapolating the curve to intercept with the abscissa.

8

Supplementary Figure 4. Measurement of interfacial fatigue threshold of common

hydrogel (PAA) adhesion to glass. Measured crack extension per cycle at applied energy

release rates of a. 25 J m-2, b. 13 J m-2, c. 11 J m-2, d. 10 J m-2 and e. 5 J m-2. f. Measured crack

extension per cycle (dc/dN) versus applied energy release rate G. The interfacial fatigue

threshold of brittle hydrogel adhesion (i.e., PAA) on glass is measured to be 9 J m-2 by linearly

extrapolating the curve to intercept with the G-axis.

9

Supplementary Figure 5. Measurement of interfacial fatigue threshold of common

hydrogel (PAAm) adhesion to glass. Measured crack extension per cycle at applied energy

release rates of a. 57 J m-2, b. 50 J m-2, c. 40 J m-2, d. 35 J m-2 and e. 20 J m-2. f. Measured

crack extension per cycle (dc/dN) versus applied energy release rate G. The interfacial fatigue

threshold of brittle hydrogel adhesion (i.e., PAAm) on glass is measured to be 32 J m-2 by

linearly extrapolating the curve to intercept with the G-axis.

10

Supplementary Figure 6. Measurement of interfacial fatigue threshold of fatigue-

resistant hydrogel adhesion to glass. Measured crack extension per cycle at applied energy

release rates of a. 1,175 J m-2, b. 1,090 J m-2, c. 800 J m-2, d. 700 J m-2 and e. 600 J m-2. f.

Measured crack extension curve in the plot of crack extension per cycle (dc/dN) versus applied

energy release rate G. The interfacial fatigue threshold of fatigue resistant hydrogel adhesion

to glass is measured to be 800 J m-2 by linearly extrapolating the curve to intercept with the G-

axis.

11

Supplementary Figure 7. Measurement of interfacial fatigue threshold of fatigue-

resistant hydrogel adhesion to glass in Dulbecco's phosphate-buffered saline. Measured

crack extension per cycle at applied energy release rates of a. 1,000 J m-2, b. 850 J m-2, c. 800

J m-2, d. 700 J m-2 and e. 600 J m-2. f. Measured crack extension curve in the plot of crack

extension per cycle (dc/dN) versus applied energy release rate G. The interfacial fatigue

threshold of fatigue resistant hydrogel adhesion to glass is measured to be 800 J m-2 by linearly

extrapolating the curve to intercept with the G-axis.

12

Supplementary Figure 8. Validation of interfacial fatigue threshold. The interfacial fatigue

threshold of fatigue-resistant hydrogel adhesion is validated as high as 785 J/m2 in PBS over

15,000 cycles of peeling test.

13

Supplementary Figure 9. Validation of high fatigue threshold of the PVA hydrogel

adhesion on a glass substrate. Images of PVA hydrogel adhered on glass at an applied energy

release rate of 800 J m-2 at the cycle number of 10,000, 20,000, and 30,000. No interfacial crack

propagation has been observed using a camera with a resolution of 20 μm per pixel. Scale bars:

1 mm.

14

Supplementary Figure 10. Fatigue failure mode of fatigue-resistant hydrogel adhesion

under the peeling test. The fatigue crack tilts on the interface and propagates into the bulk

hydrogel, accompanied by the rupture of both hydrogel and backing at an energy release rate

of 1,500 J m-2 within 173 cycles. Scale bars: 5 mm.

15

Supplementary Figure 11. Aging properties of the fatigue-resistant hydrogel adhesion to

glass. Summary of the interfacial toughness and interfacial fatigue threshold versus the aging

time when soaking in deionized water.

16

Supplementary Figure 12. Measurement of interfacial fatigue threshold of fatigue-

resistant hydrogel adhesion (i.e., PVA) to various substrates. a. 370 J m-2 for aluminium,

b. 225 J m-2 for titanium, c. 330 J m-2 for stainless steel, d. 470 J m-2 for ceramics, e. 150 J m-

2 for PDMS, and f. 420 J m-2 for PU.

17

Supplementary Figure 13. Measurement of interfacial fatigue threshold of tough

hydrogel adhesion (i.e., PAAm-alginate) to various substrates. a. 55 J m-2 for aluminium,

b. 42 J m-2 for titanium, c. 20 J m-2 for stainless steel, and d. 58 J m-2 for ceramics.

18

Supplementary Figure 14. Mechanical characterization of tough hydrogel adhesion.

Summary of measured interfacial toughness and interfacial fatigue threshold of tough hydrogel

adhesion on various solid substrates, including glass, ceramics, titanium (Ti), aluminium (Al),

stainless steel, polydimethylsiloxane (PDMS) and polyurethane (PU). *Note: data not available

since the tough hydrogel adhesion on PDMS and PU can not be achieved following the same

protocol described9. Error bars = standard deviation (n=3).

19

Supplementary Figure 15. Effect of annealing time on the fatigue-resistant hydrogel

adhesion. Summary of interfacial toughness and interfacial fatigue threshold of fatigue-

resistant hydrogel adhesion to glass with different annealing time. Error bars = standard

deviation (n=3).

20

Supplementary Figure 16. Water content and crystallinity of fatigue-resistant hydrogel

adhesion to glass with different annealing time. a. Summary of the water content of the PVA

hydrogel adhesion on glass with annealing time of 0, 1, 3, 5, 10, 90 min. b. Summary of the

crystallinity of the PVA hydrogel adhesion on glass with annealing time of 0, 1, 3, 5, 10, 90

min. Error bars = standard deviation (n=3).

21

Supplementary Figure 17. Effect of freeze-thawing cycle number on the fatigue-resistant

hydrogel adhesion. Summary of interfacial toughnesses of fatigue-resistant hydrogel adhesion

to glass with different freeze-thawing cycles before and after 90-min annealing. Error bars =

standard deviation (n=3).

22

Supplementary Figure 18. Modeling and equilibration of PVA nanocrystalline structure.

a, The initial fully atomic model of PVA nanocrystal and the fully equilibrate one. Different

elements are colored with cyan for carbon, red for oxygen, white for hydrogen, and hydrogen

bonds are highlighted by red dash lines. b, The root-mean-square deviation (RMSD) of all the

atoms’ coordinate deviated from its initial conformation during the first nanosecond of

equilibration simulation, suggesting that the structure does not change too much from its initial

conformation and starts to converge to a stable state. c, The atomic pair distribution function

(PDF) of the carbon atoms within the equilibrated PVA nanocrystal, and the existence of the

few peaks after the first peak (for the nearest C-C neighbor) suggests that the crystal structure

is in analogy to the PDF of a beta-sheet structure for an amyloid protein as inserted.

23

Supplementary Figure 19. Measurement of the friction coefficient (COF) of interfaces

between cartilage and various substrates. a, Schematic illustration of set-up for measuring

friction coefficient. b, Applied compressive normal force versus time. c, Frictional force versus

time during the cyclic sliding at the interface between the metallic supporting plate and

bearings at a set fore of 93 N. d, Frictional force versus time during cyclic sliding at the

interface between cartilage and fatigue-resistant PVA hydrogel at a set force of 70 N. e, Steady-

state frictional force versus applied normal force for the interface between metallic supporting

plate and bearings. The slope gives the frictional coefficient of the interface between the metal

substrate and bearings as 0.0028. f, Corrected frictional force versus applied normal force for

the interface between PVA hydrogel and cartilage. The slope gives the frictional coefficient of

the interface between the metal substrate and bearings as 0.014. Error bars = standard deviation

(n=3).

24

Supplementary Figure 20. The incremental frictional coefficient per cycle (d(COF)/dN) over

cycles for PVA hydrogel coating against cartilage and bare stainless steel against cartilage at

compressive force of 100 N.

25

Supplementary Figure 21. Wear of cartilages against different materials during

reciprocating sliding. a-c, Images of cartilage surfaces before (a) and after 5,000 cycles of

reciprocating sliding against bare stainless steel (b), and fatigue-resistant hydrogel coating on

stainless steel (c) with a normal compression force of 100 N (compressive stress of ~1 MPa).

The regions circled in dotted white lines show the wear of cartilage surfaces against bare

stainless steel (b). d-f, Topographic images obtained from confocal laser scanning microscopy

for the contact zone of chicken cartilage before (d) and after 5,000 cycles of reciprocating

sliding against bare stainless steel (e), and fatigue-resistant hydrogel coating (f). The colors in

d-f indicate different height. Dot lines in d-f show the location of height profiles in g-i. g-i,

Local height profiles of cartilage surfaces before (g) and after 5,000 cycles of reciprocating

sliding against bare stainless steel (h), and fatigue-resistant hydrogel coating (i). Scale bars: 5

mm in a-c.

26

Supplementary Figure 22. Wear of fatigue-resistant hydrogel coating against cartilages

during reciprocating sliding. a-b, Scanning electron microscopy images of fatigue-resistant

hydrogel coating before (a) and after (b) 5,000 cycles of reciprocating sliding against cartilage.

c-d, Confocal laser scanning microscopy images of fatigue-resistant hydrogel coating before

(c) and after (d) 5,000 cycles of reciprocating sliding against cartilage. Scale bars: 20 μm in

a,b and 500 μm in c,d.

27

Supplementary Figure 23. GIWAXS pattern of a controlled sample PVA hydrogel on a

polytetrafluoroethylene (PTFE) substrate. A uniform scattering ring is observed for PVA

hydrogel on a PTFE substrate as a control, suggesting a randomly distributed crystalline

domains, due to the absence of interfacial hydrogen bonding.

28

Supplementary Figure 24. GIWAXS curves for the PVA hydrogel adhesion to different

substrates. GIWAXS curves for the PVA hydrogels before and after annealing on glass

(100 °C, 90 min), and a PVA hydrogel annealed on PTFE (no hydrogen bonds at the interface

between hydrogel and PTFE).

29

References

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hydrogels. J. Appl. Polym. Sci. 20, 1457-1465 (1976).

2. Lin, S., et al. Anti-fatigue-fracture hydrogels. Sci. Adv. 5, eaau8528 (2019).

3. Yuk, H., Zhang, T., Lin, S., Parada, G. A., Zhao, X. Tough bonding of hydrogels to diverse

non-porous surfaces. Nat. Mater. 15, 190-196 (2016).