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We previously demonstrated that a synthetic negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induced chondrogenic differentiation of ATDC5 cells. In this study, we clarified the underlying molecular mechanism, in particular, focusing on the events that occurred at the interface between the gel and the cells. Gene expression profiling revealed that the expression of extracellular components was enhanced in the ATDC5 cells that were cultured on the PAMPS gel, suggesting that extracellular proteins secreted from the ATDC5 cells might be adsorbed in the PAMPS gel, thereby contributing to the induction of chondrogenic differentiation. Therefore, we created "Treated-PAMPS gel," which adsorbed various proteins secreted from the cultured ATDC5 cells during 7 days. Proteomic analysis identified 27 proteins, including extracellular matrix proteins such as Types I, III, and V collagens and thrombospondin (THBS) in the Treated-PAMPS gel. The Treated-PAMPS gel preferentially induced expression of chondrogenic markers, namely, aggrecan and Type II collagen, in the ATDC5 cells compared with the untreated PAMPS gel. Addition of recombinant THBS1 to the ATDC5 cells significantly enhanced the PAMPS-induced chondrogenic differentiation, whereas knockdown of THBS1 completely abolished this response. In conclusion, we demonstrated that the PAMPS gel has the potential to induce chondrogenic differentiation through novel reservoir functions, and the adsorbed THBS plays a significant role in the induction., (© 2020 Wiley Periodicals LLC.)

The high water content of hydrogels makes them important as synthetic biomaterials, and tuning the mechanical properties of hydrogels to match those of natural tissues without changing chemistry is usually difficult. In this study, we have developed a series of hydrogels with varied stiffness, strength, and toughness based on a combination of poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS), a strong acidic polyelectrolyte, and poly- N -(carboxymethyl)- N , N -dimethyl-2-(methacryloyloxy) ethanaminium) (PCDME), a polyzwitterion with a weak acidic moiety. We demonstrate that modifying the true molar ratio, R , of PCDME to PAMPS results in four unique categories of hydrogels with different swelling ratios and Young's moduli. When R < 1, a negatively charged polyelectrolyte gel (PE) is formed; when 1 < R < 3, a tough and viscoelastic polyelectrolyte complex gel (PEC) is formed; when 3 < R < 6.5, a conventional, elastic interpenetrating network gel (IPN) is formed; and when R > 6.5, a tough and stiff double-network gel (DN) is formed. Both the PEC and DN gels exhibit high toughness and fracture stress, up to 1.8 and 1.5 MPa, respectively. Importantly, the PEC gels exhibit strong recovery properties along with high toughness, distinguishing them from DN gels. Without requiring a change in chemistry, we can tune the mechanical response of hydrogels over a wide spectrum, making this a useful system of soft and hydrated biomaterials.

Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior. Furthermore, ITG α4 depletion suppressed PAMPS gel-induced expression of bone morphogenic protein (BMP) 4 contributing to chondrogenic differentiation, in concordance with the reduction of ERK activation. These results demonstrated that membrane protein binding to PAMPS gels occurred in a charge-dependent manner, and that ITG α4 plays a crucial role in cell spreading on PAMPS gels and acts as a mechanoreceptor triggering cellular signaling leads to chondrogenic differentiation., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purposes of this study were to identify signaling pathways that were specifically activated in ATDC5 cells cultured on poly (2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel in insulin-free maintenance medium and to evaluate the significance of the determined signaling pathways in the chondrogenic differentiation induced by this gel. In this study, ATDC5 cells cultured on PAMPS gel using the maintenance medium without insulin (PAMPS Culture) were compared with cells cultured on polystyrene using the differentiation medium containing insulin (PS-I Culture). The microarray analysis, Western blot analysis, and real-time PCR analysis demonstrated that the TGF-β/BMP signaling pathway was significantly enhanced at Days 1, 2, and 3 in the PAMPS Culture when compared with the PS-I Culture. Inhibition of the BMP type-I receptor reduced the phosphorylation level of Smad1/5 and expression of type-2 collagen and aggrecan mRNA in the cells accompanied by a reduction in cell aggregation at Day 13 in the PAMPS Culture. The inhibition of the TGF-β/BMP signaling pathway significantly inhibited the chondrogenic differentiation induced by the PAMPS gel. The present study demonstrated that synthetic PAMPS gel activates the TGF-β/BMP/Smad signaling pathway in the ATDC5 cells in the absence of insulin, and that this activation plays a significant role in the chondrogenic differentiation induced by PAMPS gel. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 734-746, 2016., (© 2015 Wiley Periodicals, Inc.)

A double-network (DN) gel, which was composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated the biomechanical and biological responses of chondrogenic progenitor ATDC5 cells cultured on the DN gel. ATDC5 cells were cultured on a polystyrene surface without insulin (Culture 1) and with insulin (Culture 2), and on the DN gel without insulin (Culture 3). The cultured cells were evaluated using micropipette aspiration for cell Young's modulus and qPCR for gene expression of chondrogenic and actin organization markers on days 3, 7 and 14. On day 3, the cells in Culture 3 formed nodules, in which the cells exhibited an actin cortical layer inside them, and gene expression of type-II collagen, aggrecan, and SOX9 was significantly higher in Culture 3 than Cultures 1 and 2 (p<0.05). Young's modulus in Culture 3 was significantly higher than that in Culture 1 throughout the testing period (p<0.05) and that in Culture 2 on day 14 (p<0.01). There was continuous expression of actin organization markers in Culture 3. This study highlights that the cells on the DN gel increased the modulus and mRNA expression of chondrogenic markers at an earlier time point with a greater magnitude compared to those on the polystyrene surface with insulin. This study also demonstrates a possible strong interrelation among alteration of cell mechanical properties, changes in actin organization and the induction of chondrogenic differentiation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Recently, several animal studies have found that spontaneous hyaline cartilage regeneration can be induced in vivo within a large osteochondral defect by implanting a synthetic double-network (DN) hydrogel, which is composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and poly-(N,N'-dimethyl acrylamide) (PDMAAm), at the bottom of the defect. However, the effect of hydrogel on hyaline cartilage regeneration remains unexplained. The purpose of this study was to investigate the chondrogenic differentiation of C3H10T1/2 cells on PAMPS/PDMAAm DN gel., Methods: C3H10T1/2 cells of 1.0 × 105 were cultured on PAMPS/PDMAAm DN gel in polystyrene tissue culture dishes or directly on polystyrene tissue culture dishes. We compared cultured cells on PAMPS/PDMAAm DN gel with those on polystyrene dishes by morphology using phase-contrast microscopy, mRNA expression of aggrecan, type I collagen, type II collagen, Sox 9 and osteocalcin using real-time RT-PCR, and local expression of type II collagen using immunocytochemistry., Results: C3H10T1/2 cells cultured on the PAMPS/PDMAAm DN gels formed focal adhesions, aggregated rapidly and developed into large nodules within 7 days, while the cells cultured on the polystyrene surface did not. The mRNA levels of aggrecan, type I collagen, type II collagen, Sox 9 and osteocalcin were significantly greater in cells cultured on the PAMPS/PDMAAm DN gel than in those cultured on polystyrene dishes. In addition, C3H10T1/2 cells cultured on PAMPS/PDMAAm DN gel expressed more type II collagen at the protein level when compared with cells cultured on polystyrene dishes., Conclusions: The present study showed that PAMPS/PDMAAm DN gel enhanced chondrogenesis of C3H10T1/2 cells, which are functionally similar to mesenchymal stem cells. This suggests that mesenchymal stem cells from the bone marrow contribute to spontaneous hyaline cartilage regeneration in vivo in large osteochondral defects after implantation of PAMPS/PDMAAm DN gels.

Background: A double-network (DN) gel, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated whether DN gel induced chondrogenic differentiation of ATDC5 cells in a maintenance medium without insulin, and whether supplementation of hyaluronic acid enhanced the chondrogenic differentiation effect of DN gel., Methods: ATDC5 cells were cultured on the DN gel and the polystyrene (PS) dish in maintenance media without insulin for 21 days. Hyaluronic acid having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.01, 0.1, or 1.0 mg/mL. The cultured cells were evaluated using immunocytochemistry for type-2 collagen and real time PCR for gene expression of type-2 collagen, aggrecan, and Sox9 at 7 and 21 days of culture., Results: The cells cultured on the DN gel formed nodules and were stained with an anti-type-2 collagen antibody, and expression of type-2 collagen and aggrecan mRNA was significantly greater on the DN gel than on the PS dish surface (p < 0.05) in the hyaluronic acid-free maintenance medium. Hyaluronic acid supplementation of a high concentration (1.0 mg/mL) significantly enhanced expression of type-2 collagen and aggrecan mRNA in comparison with culture without hyaluronic acid at 21 days (p < 0.05)., Conclusions: The DN gel induced chondrogenic differentiation of ATDC5 cells without insulin. This effect was significantly affected by hyaluronic acid, depending on the level of concentration. There is a high possibility that hyaluronic acid plays an important role in the in vivo hyaline cartilage regeneration phenomenon induced by the DN gel.

Based on the molecular stent concept, a series of tough double-network hydrogels (St-DN gels) made from the components of proteoglycan aggregates - chondroitin sulfate proteoglycans (1), chondroitin sulfate (2), and sodium hyaluronate (3) - are successfully developed in combination with a neutral biocompatible polymer. This work demonstrates a promising method to create biopolymer-based tough hydrogels for biomedical applications., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: It has been a common belief that articular cartilage tissue cannot regenerate in vivo. Recently, however, we have found that spontaneous hyaline cartilage regeneration can be induced in vivo by implanting a synthetic double-network (DN) hydrogel, which is composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and poly-(N,N'-dimethyl acrylamide) (PDMAAm). However, the mechanism of this phenomenon has not been clarified. Recently, we have found that single-network PAMPS and PDMAAm gels can induce chondrogenic differentiation of ATDC5 cells in vitro even in a maintenance medium. In the in vivo condition, there is a strong possibility that the induction effect of the gel itself is enhanced by some molecules which exist in the joint. We have noticed that the joint fluid naturally contains hyaluronic acid (HA). The purpose of this study is to clarify in vitro effects of supplementation of HA on the differentiation effect of the PAMPS and PDMAAm gels., Methods: We cultured the ATDC5 cells on the PAMPS gel, the PDMAAm gel, and the polystyrene (PS) dish surface with the maintenance medium without insulin for 7 days. HA having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.00, 0.01, 0.10, or 1.00 mg/mL. We evaluated the cultured cells with phase-contrast microscopy and PCR analyses., Results: On the PAMPS gel, supplementation with HA of 0.01 and 0.10 mg/mL significantly increased expression of type-2 collagen mRNA (p = 0.0008 and p = 0.0413) and aggrecan mRNA (p = 0.0073 and p = 0.0196) than that without HA. On the PDMAAm gel, supplementation with HA of 1.00 mg/mL significantly reduced expression of these genes in comparison with the culture without HA (p = 0.0426 and p = 0.0218)., Conclusions: The in vitro induction effects of the PAMPS and PDMAAm gels on chondrogenic differentiation of ATDC5 cells are significantly affected by HA, depending on the level of concentration. These results suggested that there is a high possibility that HA plays an important role in the in vivo spontaneous hyaline cartilage regeneration phenomenon induced by the PAMPS/PDMAAm DN gel.

Background: A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration., Methods: Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks., Results: According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p<0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p<0.05) than that in Group IV., Conclusions: The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

The purpose of this study was to determine the in vivo cartilage induction effect of the poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) single-network (SN) gel and poly(N,N'-dimethyl acrylamide) (PDMAAm) SN gel in comparison with that of the PAMPS/PDMAAm double-network (DN) gel. An osteochondral defect created in rabbit trochlea was treated with PAMPS/PDMAAm DN, PAMPS SN, or PDMAAm SN gel implantation or left untreated. The gel was implanted into the defect so that a 2-mm depth remained. The defects were examined by histologic and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction analysis at 4 weeks. Samples were quantitatively evaluated with a scoring system reported by Wayne et al. The PAMPS/PDMAAm DN gel-implanted defect was filled with the hyaline-like cartilage tissue. The PAMPS SN gel-implanted defect was filled inhomogenously with hyaline/fibrocartilage tissue. The histology score of the defect treated with PAMPS/PDMAAm DN gel was significantly higher than those treated with PAMPS and PDMAAm SN gels, and the untreated defect (p = 0.0408, p < 0.0001, and p < 0.0001, respectively) and the scores of the defect treated with PAMPS SN gel were significantly higher than those treated with PDMAAm SN gel and the untreated defect (p = 0.0026 and p = 0.0026, respectively). These results suggested that the PAMPS SN gel has an ability that can induce hyaline cartilage regeneration in vivo, but that the PDMAAm SN gel does not. The current study indicates that the chondrogenic potential of a negatively charged PAMPS gel component plays an important role in the cartilage regeneration ability of the PAMPS/PDMAAm DN gel in vivo., (Copyright © 2012 Wiley Periodicals, Inc.)

We studied the ability of surfactants to reduce friction by boundary lubrication for a bulk hydrogel sliding on a solid surface in an aqueous solution. A piece of negatively charged polyelectrolyte hydrogel was slid across solid surfaces with various levels of hydrophobicity, using a strain-controlled parallel-plate rheometer in water. A dramatic reduction in the sliding friction, especially in the low velocity region, was detected by the addition of a surfactant to the water medium. This friction reduction was only observed in gel-solid friction but not in solid-solid friction, indicating that the soft and wet nature of the gel surface was crucial for this surfactant-induced friction reduction. This phenomenon reveals that surfactants can remain at the gel-mated interface, thus preventing direct interfacial interaction between the sliding surfaces, and significantly decreasing the frictional stress. The reported dramatic reduction in friction highlights the frictional characteristics of soft and wet hydrogel materials.

Background: A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo., Purpose: To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel., Study Design: Controlled laboratory study., Methods: A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al., Results: The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel-implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees., Conclusion: This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds., Clinical Relevance: This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

A hydrogel with cylindrically symmetric structure at macroscopic scale has been developed by polymerization of a cationic monomer in the presence of a small amount of semi-rigid polyanion poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) in a cylinder glass tube. The polyion complex radially aligns in the outer region of the synthesized cylinder gel. On the other hand, it orients in concentric and axial directions in the inner region. To the authors' knowledge, this is the first report of such millimeter-scale ordered structure developed in a polymeric hydrogel. We elucidate that homeotropic alignment on the glass wall is energetically favorable for the semi-rigid polyion complex, resulting in the radial orientation in the outer region. In the inner region, the oriented structures result from the monomer difffusion (due to the heterogeneous polymerization) that induces PBDT orientation perpendicular to the diffusion direction. The structured gels showing sensitive response of birefringence to external force are expected to find applications in optical sensors.

This study evaluated the in vivo influence of a poly-(2-Acrylamido-2-methylpropane sulfonic acid)/poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm) double-network (DN) hydrogel on counterface cartilage in rabbit knee joints and its ex vivo friction properties on normal cartilage. In the first experiment, the DN gel was implanted in a surgically created defect in the femoral trochlea of rabbit knee joints and the left knee was used as the control. Evaluations using a confocal laser scanning microscopy demonstrated that the DN gel did not affect the surface microstructure (surface roughness, the number of small pits) of the counterface cartilage in vivo at 4 and 12 weeks. The histology also showed that the DN gel hadno pathological damage on the cartilage matrices and cells at 4 weeks. However, two of the five DN gel-implanted knees showed mild irregularity on the counterface cartilage surface at 12 weeks. In the second experiment, the friction property between the normal and the artificial cartilage was determined using a joint simulator apparatus. The ex vivo mean friction coefficient of the DN gel to normal cartilage was 0.029, while that of the normal-to-normal cartilage articulation was 0.188. The coefficient of the DN gel-to-normal cartilage articulation was significantly lower than that of the normal-to-normal cartilage articulation (p < 0.0001). This study suggested that the PAMPS/PDMAAm DN gel has very low friction coefficient on normal cartilage and has no significant detrimental effects on counterface cartilage in vivo, and can be a promising material to develop the artificial cartilage.

We have developed a novel method to induce spontaneous hyaline cartilage regeneration in vivo for a large osteochondral defect by implanting a plug made from a double-network hydrogel composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethylacrylamide) at the bottom of the defect, leaving the cavity vacant. In cells regenerated in the treated defect, type-2 collagen, Aggrican, and SOX9 mRNAs were highly expressed and the regenerated matrix was rich in proteoglycan and type-2 collagen at 4 weeks. This fact gave a significant modification to the commonly established concept that hyaline cartilage tissue cannot regenerate in vivo. This study prompted an innovative strategy in the field of joint surgery to repair an osteochondral defect using an advanced, high-function hydrogel.

The fracture energy G of double network (DN) gels, consisting of poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) as the first network and poly(acrylamide) (PAAm) as the second network, was measured by the tearing test as a function of the crack velocity V. The following results were obtained: (i) The fracture energy G ranges from 10(2) to approximately 10(3) J/m2, which is 100-1000 times larger than that of normal PAAm gels (10(0) J/m2) or PAMPS gels (10(-1) J/m2) with similar polymer concentrations to the DN gels. (ii) G shows weak dependence on the crack velocity V. (iii) G at a given value of V increases with decreasing of cross-linking density of the 2nd network. The measured values of G were compared with three theories that describe different mechanisms enhancing the fracture energy of soft polymeric systems. A mechanism relating to a heterogeneous structure of the DN gel is convincing for the remarkable large values of G.

This study investigated whether hydrogels comprising hydrophilic cationic polymers have similar bactericidal effects. Bacteria were seeded on hydrogels and agar and their viability was assessed with time. Cationic hydrogels displayed bactericidal effects upon long‐term bacterial contact. Furthermore, we assessed the areal density of cationic monomer unit of the cationic hydrogels, water content, and the initial elastic modulus. We examined correlations between each factor and bacterial death ratios; consequently, the bacterial death ratios were strongly correlated with the areal density of cationic hydrogel monomers. Elastic energy (Wel) generated at the cytomembrane ion‐binding region and the cationic hydrogel and the cytomembrane interfacial energy (Wf) were estimated; consequently, Wel exceeded Wf at higher contact areas. The cationic hydrogel may extract cytomembranes with a reasonable adsorption area. Therefore, cationic hydrogels may be used as probes for ultrasonic echo to sterilize medical equipment. [ABSTRACT FROM AUTHOR]

Creep rupture (plasticity controlled failure) and slow crack growth are two important failure mechanisms that limit the lifetime of polymer constructions under load. Since both require different approaches to predict lifetime or improve the materials performance, the identification of the active mechanism is essential. Problems arise when the macroscopic failure mode is identical (i.e. brittle) in both cases (e.g. in composite systems). In this study, it is shown that both mechanisms can be distinguished effectively by comparing lifetimes in static and cyclic fatigue. At equal value of the maximum load, plasticity-controlled failure is postponed in cyclic loading, whereas crack propagation is significantly accelerated. The origin of this specific response is discussed, and its generic character demonstrated for a great variety of engineering polymers. [ABSTRACT FROM AUTHOR]