Journal Club for July 2020: Fatigue-resistant hydrogels: Principles, Experiments, and Applications

  

 

Fatigue-resistant hydrogels: Principles, Experiments, and Applications

Shaoting Lin, Xuanhe Zhao

1.     Introduction

The use of hydrogels in devices and machines requires them to maintain robustness under cyclic mechanical loads [1, 2]. Hydrogels have been made tough to resist crack propagation under a single cycle of mechanical load [3, 4]. In general, the toughening of hydrogels is achieved by integrating mechanisms for dissipating mechanical energy such as the fracture of short polymer chains and reversible cross-links into stretchy polymer networks [5, 6].

Figure 1. Fatigue threshold of A), conventional polymer networks for elastomers and hydrogels and B), biological hydrogels with intrinsically high-energy phases such as nanocrystalline domains and nanofibers.

Despite the progress of tough hydrogels, existing tough hydrogels suffer from fatigue fracture under multiple cycles of mechanical loads revealed by Tang, Bai, and Suo et al [7-9]. (Please refer to the Journal club of Fatigue of hydrogels in May 2019 by Ruobing Bai for details.) Their experimental findings conclude that the resistance to fatigue crack propagation after prolonged cycles of loads is the energy required to fracture a single layer of polymer chains (i.e., the intrinsic fracture energy of the hydrogel) (Fig. 1A), which is unaffected by the additional dissipation mechanisms introduced in tough hydrogels. These findings are reminiscent of fatigue of elastomers, which has been intensively studied since 1958 by Lake, Thomas, and Lindley [10-12]. 

Following the classical Lake-Thomas theory [10], the fatigue resistance of hydrogels with conventional polymer networks can be estimated by

where  n*sqrt(N)*b/(λs)^2 is the number of polymer chains per unit area with n being the number density of active polymer chains per unit volume in the dry state, N being the number of Kuhn monomer per polymer chain, b being the length of each Kuhn monomer, and λs being the swelling stretch of polymer chains, N*Uf is the energy required to fracture a polymer chain with Uf being the energy required to fracture a single Kuhn monomer. For hydrogels with conventional networks, the reasonable ranges for these parameters are n~10^25-10^26 m-3, N~100-1000, b~0.3 nm, λs~2-10, and Uf~10^6 J/mol [8, 13-16]. By substituting the values of these parameters into Eq. (1), we can evaluate the typical range of the fatigue resistance of hydrogels with conventional polymer networks on the order of 1-100 J/m^2, which is far below fracture energies of tough hydrogels on the order of 1,000 J/m^2 [5]. Strategies toward the design of anti-fatigue-fracture hydrogels have remained critical needs and central challenges for long-term applications of hydrogels in devices and machines. 

In contrast to synthetic hydrogels, biological tissues such as cartilages, tendons, muscles, and heart valves show extraordinary anti-fatigue properties. The anti-fatigue property of biological tissues possibly arises from its inherent highly ordered and partially crystalline structures of collagen fibers in the tissues. For instance, the adhesions of tendons, ligaments, and cartilages to bones are commonly achieved through a transitional interface (Fig. 1B), from the uncalcified collagen nanofibrils (i) to the calcified collagen nanofibrils (ii) to the bones (iii). At the interface (ii), nanostructured composites of aligned collagen nanofibrils and ordered hydroxyapatite nanocrystals are anchored on the bones, leading to fatigue-resistant adhesions of tendons, ligaments, and cartilages to the bones [17,18]. The cartilage-bone interface in the human knee joint can sustain compressive stresses of 1 MPa along with an interfacial toughness around 800 J/m2 over 1 million cycles of loading per year.

Taking the opportunity of this journal club, we would like to discuss i) design principle for fatigue-resistant hydrogels, ii) symptoms of interfacial fatigue of hydrogel adhesions, iii) design principle for fatigue-resistant hydrogel adhesions, and iv) applications of fatigue-resistant hydrogels and hydrogel adhesions.

2.     Fatigue-resistant hydrogels

To address the challenge of fatigue failures in conventional hydrogels, we and others propose the general design principle for fatigue-resistant hydrogels: Make the fatigue crack pinned by intrinsically high-energy phases [19], such as nanocrystals [20], micro-/nano-fibers [21], and macro-fibers [22] in hydrogels. In what follows, we will summarize the recently reported strategies to implement the design principle. 

Our experimental finding first suggests the increase of crystallinity in synthetic hydrogels can substantially enhance their fatigue thresholds because of the need to fracture crystalline domains for fatigue crack propagation (Fig. 2A) [20]. The energy per unit area required to fracture crystalline domains of a polymer is much higher than that required to fracture a single layer of amorphous chains of the same polymer. To test the hypothesis, we select PVA as a model hydrogel with tunable crystallinity. We find that the increase of crystallinity can greatly enhance the fatigue thresholds of PVA hydrogels due to the decrease of the average distance between adjacent crystalline domains and the increase of the average size of the crystalline domains. In particular, the fatigue threshold can exceed 1000 J/m2 when the crystallinity of PVA in the swollen state reaches 18.9 wt % (Fig. 2A).  

While the introduction of crystalline domains can greatly enhance the fatigue threshold, it increases the modulus and decreases the water content of the hydrogel. Thereby, we come up with the other strategy via mechanical training to enhance hydrogels’ fatigue resistance while maintaining its low modulus [21]. The strategy first involves growing compliant nanofibrils in PVA hydrogels by forming two separated phases via repeated cycles of freezing and thawing [23]: (i) high concentration of polymer chains in the form of nanofibrils cross-linked by nanocrystalline domains and (ii) low concentration of amorphous. The pristine freeze-thawed hydrogels with randomly distributed nanofibrils are exposed to repeated prestretches in a water bath as mechanical training, to form aligned nanofibrillar structures (Fig. 2B). The fatigue threshold of the trained PVA hydrogel measured along the aligned nanofibrils reaches a record-high value of 1,250 J/m2 (Fig. 2B). By contrast, the fatigue threshold perpendicular to the aligned nanofibrils is 233 J/m2, which is on the same order as that of the pristine freeze-thawed PVA hydrogel (i.e., 310 J/m2), but still much larger than that of the chemically cross-linked PVA hydrogel (i.e., 10 J/m2).

Figure 2 Strategies for fatigue-resistant hydrogels

More recently, Wang and Suo et al. [22] reported a new principle to enhance elastomer’s fatigue resistance by introducing unidirectional fibers in the soft matrix (Fig. 2C). Both the fibers or the matrix have a low fatigue threshold. The combination of the fibers and the matrix shows a remarkable high fatigue threshold, because the soft matrix deconcentrates stress in the fiber. They demonstrate the strategy by embedding fibers of a polydimethylsiloxane (PDMS) elastomer into a matrix of a polyacrylamide (PAAm) hydrogel. No damage is observed when the composite is stretched for 30000 cycles with an amplitude of the energy release rate of 1290 J/m2. By harnessing the capability of 3D printing, Tang and Suo et al. further expanded the principle into two-dimensional elastomeric lattices, reaching the fatigue threshold beyond 500 J/m2 in multiple directions [24].  

We would like to also highlight recent work by Li and Gong et al. [25]. In this work, they study antifatigue properties of soft materials with hierarchical structures and reveal the mechanism of the hierarchical structures on suppressing crack advance under reciprocating movement (Fig. 2D). Using polyampholyte hydrogels (PA gels) as a simple model system with a hierarchical structure, they demonstrate a high fatigue resistance through a synergistic effect between different scales. Particularly, they find that the polymer network at the 10-nm scale determines the threshold of energy release rate G0 above which the crack grows, while the bicontinuous phase networks at the 100-nm scale significantly decelerate the crack advance until a transition Gtran far above G0. Such understanding may shed light on designing synthetic hydrogels that can truly replicate load-bearing biological tissues, composed of exquisite hierarchical structures. 

3.     Fatigue-resistant hydrogel adhesions

3.1 Symptoms of interfacial fatigue of hydrogel adhesions

Tough adhesions between hydrogels and engineering materials have been achieved by covalently anchoring polymer chains of tough hydrogels on solid surfaces [26]. When the hydrogel is peeled from the solid under a single cycle of the mechanical load, the energy required for fracturing anchored polymer chains and the energy dissipated in deforming the bulk hydrogel synergistically give an interfacial toughness over 1000 J/m2. We recently characterized fatigue properties of tough hydrogel adhesion to glass substrates. As shown in Fig. 3A-C, the interfacial fatigue threshold of tough hydrogel adhesion (PAAm-alginate) is as low as 68 J/m2, similar to that of common hydrogel adhesion (9 J/m2 for PAA and 32 J/m2 for PAAm), and comparable with the energy required for fracturing a layer of amorphous polymer chains (1-100 J/m2). When the tough hydrogel adhesion is subjected to an energy release rate of 200 J/m2 over 5000 cycles, substantial propagation of the interfacial cohesive crack can be identified. 

 Figure 3 Symptoms of interfacial fatigue of hydrogel adhesion

Similarly, Ni and Li et al. [27] observed the interfacial fatigue of hydrogel adhesions to biological tissues (Fig. 3D-E). They performed modified lap-shear tests with three types of loading (e.g., monotonic, static, and cyclic loads). They observed shakedown of the load-displacement curves during cycling and two interfacial fracture phenomena: fast debonding and interfacial fatigue fracture. They further confirmed the existence of a fatigue threshold (24.4 J/m2) for the tough hydrogel-tissue interface, below which the interface is immune against prolonged cyclic deformation. 

3.2 Design principle for fatigue-resistant hydrogel adhesions

We recently proposed a bioinspired strategy to achieve fatigue-resistant adhesions of synthetic hydrogels by anchoring ordered nanostructures (e.g., nanocrystalline domains) on engineering materials, since the ordered nanostructures require a much higher energy for fatigue-crack propagation than the corresponding amorphous polymer chains (Fig. 4A-B). We chose poly(vinyl alcohol) (PVA) hydrogels as a model material system, which can readily form nanostructures (e.g., nanocrystalline domains and nanofibrils) with tunable crystallinity. The anchorage of nanocrystalline domains on solid substrates through dry-annealing treatment gives a remarkable fatigue-resistant adhesion between hydrogels and substrates, with an interfacial fatigue threshold of 700 J/m^2 (Fig. 4C). This method is applicable to diverse engineering solids including glass, ceramics, Titanium, aluminum, stainless steel, and even elastomers such as PU and PDMS (Fig. 4D). To understand the high interfacial fatigue threshold by ordered crystalline domains at the interface, we further carried out all-atom molecular dynamics (MD) simulations to compare the energies required to pull out a PVA polymer chain (30 nm in contour length) from a nanocrystalline domain and to fracture an amorphous PVA polymer chain of the same contour length (Fig. 4E). As shown in Fig. 4F-G, pulling out of a PVA chain between the nanocrystal–glass interface requires a higher energy (~70,000 kJ/mol, PVA–SiO2) than that out of a standalone nanocrystal (~50,000 kJ/mol), which is consistent with our observation that the bulk hydrogel fractures during the peeling test, other than interfacial detachment. Therefore, introducing nanocrystalline domains on the interface and within the bulk hydrogel synergistically ensures a hydrogel–solid interface with extremely high fatigue resistance.

 Figure 4 Anchoring ordered nanocrystalline domains at the interface

Lu and Suo et al. [28] reported a different approach for the design of fatigue-resistant hydrogel adhesion by using a particularly simple kind of elastic dissipater: long-chain polymers (Fig. 5A). As a proof of concept, they used polyacrylamide hydrogels to adhere two pieces of polyester cloth through topological entanglement. The measured fatigue threshold of the adhesion is linearly proportional to the square root of the chain length and reaches 300 J/m2 (Fig. 5B).

Figure 5 Long-chain polymers as elastic dissipaters 

4.     Applications 

Fatigue-resistant hydrogels open up many opportunities for applications in biomedical areas. A nascent field named hydrogel machines has rapidly evolved, suggesting potentials for using fatigue-resistant hydrogels to complement or even replace many conventional machines based on rigid materials [2]. 

4.1 Ingestible gastro-retentive device

Devices that interact with living organisms are typically made of metals, silicon, ceramics, and plastics. Implantation of such devices for long-term monitoring or treatment generally requires invasive procedures. Hydrogels offer new opportunities for human-machine interactions due to their superior mechanical compliance and biocompatibility. Additionally, oral administration, coupled with gastric residency, serves as a non-invasive alternative to implantation (Fig. 6A). Achieving gastric residency with hydrogels requires the hydrogels to swell very rapidly and to withstand gastric mechanical forces over time (Fig. 6B). However, high swelling ratio, high swelling speed, and long-term robustness do not coexist in existing hydrogels. 

Based on the fatigue-resistant hydrogels we developed, we invented a hydrogel device that can be ingested as a standard-sized pill, swell rapidly into a large soft sphere, and maintain robustness under repeated mechanical loads in the stomach for up to one month. The hydrogel device consists of superabsorbent hydrogel particles that enable the device to quickly imbibe water (instead of diffusion) encapsulated in a soft yet anti-fatigue hydrogel membrane that maintains long-term robustness of the device. The hydrogel device can be ingested as a standard-sized pill (diameter of 1–1.5 cm), rapidly imbibe water and inflate (up to 100 times in volume within 10 min) into a large soft sphere (diameter of up to 6 cm, Video 1) (Fig. 6C), and maintain robustness under repeated mechanical loads over a long time (more than 26,000 cycles of 20 N force over 2 weeks in vitro) (Fig. 6D). In comparison, we show that the hydrogel device made of common tough hydrogels (i.e., PAAm-agar) degrades within 8 hours on the 1st day of testing. Owing to the high fatigue resistance of the hydrogel encapsulation membrane, we successfully demonstrated gastric retention of the hydrogel device for up to 30 days in a large porcine model. Such a platform could bring a number of societal impacts including but not limited to long-term measurements of biosignals (Fig. 6E), visualizing GI tract disorders, inducing satiety to control obesity, and prolonged drug delivery. Other recent works in this area include Liu, Giovanni, and Langer et al. [29], Raman and Giovanni, et al. [30].

Figure 6 Ingestible hydrogel pills as a gastro-retentive device

4.2 Robust coatings of biomedical implants

Materials and devices with complex shapes can be exposed to repeated mechanical loads, which pose a challenge to their coating materials in terms of fabrication method and long-term robustness. We demonstrate that the fatigue-resistant hydrogel adhesion can potentially provide a facile and versatile solution towards this challenge. We first present a set of materials and devices, including a stainless-steel spring, a glass optical fiber, a glass tube, and a ball-and-socket metallic joint, which are coated with a fatigue-resistant hydrogel coating layer (Fig. 7A). The thin (~20 μm in thickness) and uniform hydrogel coatings are applicable to devices with various feature sizes (from 200 μm to 35 mm), curvatures (convex surface, concave surface, and inner and outer surfaces), and diverse materials (glass, stainless steel, and silicone elastomer). We further adopt the ball-on-flat sliding test to evaluate the adhesion, friction, and wear performances of our fatigue-resistant hydrogel coating on a stainless-steel surface over cyclic mechanical loading (Fig. 7B-C). The fatigue-resistant hydrogel coating remains mechanically robust and adheres on the substrate over 5000 cycles of reciprocating motion (Video 2). As shown in Fig. 7D, the friction coefficient of the fatigue-resistant hydrogel coating increases from 0.006 to 0.02 and maintains around 0.02 until the end of the test (5000 cycles). In comparison, the friction coefficient of the bare metal surface increases from 0.045 to as high as 0.3 as the cycle number increases from 1 to 300 (under a compression force of 100 N), and remain constant afterwards.

Figure 7 Robust coatings of biomedical implants

5.     Challenge and Opportunity

The area of fatigue-resistant hydrogels faces a number of challenges and opportunities. Efforts in the field of experimental mechanics, multi-scale modeling, material synthesis, advanced fabrications, and translational science are particularly welcome for pushing both the fundamental understanding and translational application.

Experimental mechanics. Advanced techniques for probing chain fracture [31], mapping stress [32], and quantifying topological defects [33] are highly desirable for the in-depth understanding of fatigue of hydrogels.

Related Journal Club

1. Aug 2017, Fracture mechanics of soft dissipative materials, Rong Long

2. April 2019, Self-healing soft materials: from theoretical modeling to additive manufacturing, Qiming Wang

Modeling. Multi-scale modeling that accounts for biomimetic hierarchical and heterogeneous structures [34, 35] may open a new avenue for the next generation of tissue-like hydrogels.  

Chemistry. Structural design of hydrogels (e.g. ideal network hydrogel [36]) provides model material systems for fundamental investigations. 

Translational science. The ultimate goal is to transform the fundamental understanding of synthetic hydrogels for translational applications. Representative examples include recent work of wet tissue adhesives [37].

 Related Journal Club:

1. June 2020, Mechanically instructive biomaterials: a synergy of mechanics, materials and biology, Jianyu Li

2. Dec 2018, Bonding hydrophilic and hydrophobic soft materials for functional soft devices, Qihan Liu 

6. References 

1.    Yang, C. and Z. Suo, Hydrogel ionotronics. Nature Reviews Materials, 2018. 3(6):p. 125.

2.    Liu, X., et al., Hydrogel machines. Materials Today, 2020.

3.    Gong, J.P., et al., Double‐network hydrogels with extremely high mechanical strength. Advanced materials, 2003. 15(14): p. 1155-1158.

4.    Sun, J.-Y., et al., Highly stretchable and tough hydrogels. Nature, 2012. 489(7414): p. 133-136.

5.    Zhao, X., Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks. Soft matter, 2014. 10(5): p. 672-687.

6.    Gong, J.P., Why are double network hydrogels so tough? Soft Matter, 2010. 6(12): p. 2583-2590.

7.    Bai, R., J. Yang, and Z. Suo, Fatigue of hydrogels. European Journal of Mechanics-A/Solids, 2019. 74: p. 337-370.

8.    Tang, J., et al., Fatigue fracture of hydrogels. Extreme Mechanics Letters, 2017. 10: p. 24-31.

9.    Bai, R., et al., Fatigue fracture of tough hydrogels. Extreme Mechanics Letters, 2017. 15: p. 91-96.

10.   Lake, G. and A. Thomas, The strength of highly elastic materials. Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences, 1967. 300(1460): p. 108-119.

11.   Thomas, A., Rupture of rubber. V. Cut growth in natural rubber vulcanizates. Journal of Polymer Science, 1958. 31(123): p. 467-480.

12.   Lake, G. and P. Lindley, The mechanical fatigue limit for rubber. Journal of Applied Polymer Science, 1965. 9(4): p. 1233-1251.

13.   Zhao, X., A theory for large deformation and damage of interpenetrating polymer networks. Journal of the Mechanics and Physics of Solids, 2012. 60(2): p. 319-332.

14.   Lin, S., Tissue-like hydrogels by design. 2019, Massachusetts Institute of Technology.

15.   Mao, Y., B. Talamini, and L. Anand, Rupture of polymers by chain scission. Extreme Mechanics Letters, 2017. 13: p. 17-24.

16.   Akagi, Y., et al., Fracture energy of polymer gels with controlled network structures. The Journal of chemical physics, 2013. 139(14): p. 144905.

17.   Genin, G.M. and S. Thomopoulos, The tendon-to-bone attachment: Unification through disarray. Nature materials, 2017. 16(6): p. 607-608.

18.   Rossetti, L., et al., The microstructure and micromechanics of the tendon–bone insertion. Nature materials, 2017. 16(6): p. 664-670.

19.   Zhao, X., EML webinar overview: Extreme mechanics of soft materials for merging human-machine intelligence. Extreme Mechanics Letters, 2020: p. 100784.

20.   Lin, S., et al., Anti-fatigue-fracture hydrogels. Science advances, 2019. 5(1): p. eaau8528.

21.   Lin, S., et al., Muscle-like fatigue-resistant hydrogels by mechanical training. Proceedings of the National Academy of Sciences, 2019. 116(21): p. 10244-10249.

22.   Xiang, C., et al., Stretchable and fatigue-resistant materials. Materials Today, 2019.

23.   Hassan, C.M. and N.A. Peppas, Structure and morphology of freeze/thawed PVA hydrogels. Macromolecules, 2000. 33(7): p. 2472-2479.

24.   Li, C., et al., Fatigue-resistant elastomers. Journal of the Mechanics and Physics of Solids, 2020. 134: p. 103751.

25.   Li, X., et al., Mesoscale bicontinuous networks in self-healing hydrogels delay fatigue fracture. Proceedings of the National Academy of Sciences, 2020. 117(14): p. 7606-7612.

26.   Yuk, H., et al., Tough bonding of hydrogels to diverse non-porous surfaces. Nature materials, 2016. 15(2): p. 190-196.

27.   Ni, X., C. Chen, and J. Li, Interfacial fatigue fracture of tissue adhesive hydrogels. Extreme Mechanics Letters, 2020. 34: p. 100601.

28.   Zhang, W., et al., Fatigue-resistant adhesion I. Long-chain polymers as elastic dissipaters. Extreme Mechanics Letters, 2020: p. 100813.

29.   Liu, J., et al., Triggerable tough hydrogels for gastric resident dosage forms. Nature communications, 2017. 8(1): p. 1-10.

30.   Raman, R., et al., Light-degradable hydrogels as dynamic triggers for gastrointestinal applications. Science advances, 2020. 6(3): p. eaay0065.

31.   Ducrot, E., et al., Toughening elastomers with sacrificial bonds and watching them break. Science, 2014. 344(6180): p. 186-189.

32.   Chen, Y., et al., From force-responsive molecules to quantifying and mapping stresses in soft materials. Science Advances, 2020. 6(20): p. eaaz5093.

33.   Zhong, M., et al., Quantifying the impact of molecular defects on polymer network elasticity. Science, 2016. 353(6305): p. 1264-1268.

34.   Gautieri, A., et al., Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up. Nano letters, 2011. 11(2): p. 757-766.

35.   Qin, Z. and M.J. Buehler, Flaw tolerance of nuclear intermediate filament lamina under extreme mechanical deformation. Acs Nano, 2011. 5(4): p. 3034-3042.

36.   Sakai, T., et al., Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules, 2008. 41(14): p. 5379-5384.

37.   Yuk, H., et al., Dry double-sided tape for adhesion of wet tissues and devices. Nature, 2019. 575(7781): p. 169-174.