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In contrast, most synthetic hydrogels rely solely on increasing fatigue thresholds and fracture rapidly once cracks start to propagate. Here, we realize fatigue damage tolerance design (FDT) for hydrogels via the synergy of two kinetically distinct metal\u2013ligand crosslinks. Under cyclic loads, the strong and irreversible crosslinks break to dissipate energy, shielding the weak and reversible crosslinks to re-associate upon unloading. The synergistic kinetic effects between these two crosslinks lead to the formation of a large inelastic zone at the crack tip, deconcentrating stress and significantly decelerating fatigue crack growth. The as-synthesized hydrogel exhibits outstanding fatigue resistance, with a threshold of 680 J\/m2 and an ultraslow crack growth of 1.08 mm after 106 cycles under an energy release rate of 1000 J\/m2. Remarkably, even at a higher energy release rate of \u223c3000 J\/m2, the fatigue crack growth rate remains below 10\u20137 m\/cycle. This extremely slow crack growth leads to the anti-fatigue hydrogel with a long lifespan under a broad range of the applied load level. The synergistic design of kinetically distinct metal\u2013ligand crosslinks provides a framework for fatigue-resistant soft materials.<\/jats:p>","DOI":"10.1021\/acsami.6c08899","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:14:11Z","timestamp":1785849251000},"page":"43099-43108","source":"Crossref","is-referenced-by-count":1,"title":["Fatigue Damage-Tolerant Hydrogel Engineered via Synergy of Kinetically Distinct Metal\u2013Ligand Crosslinks"],"prefix":"10.1021","volume":"18","author":[{"given":"Yijian","family":"Zheng","sequence":"first","affiliation":[{"name":"School of Aerospace Engineering, Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Aerospace Engineering, Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Aerospace Engineering, Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-7978","authenticated-orcid":true,"given":"Tongqing","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Aerospace Engineering, Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026081917073260900_cit1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1152\/physrev.00036.2019","article-title":"Cardiac mechano-electric coupling: Acute effects of mechanical stimulation on heart rate and rhythm","volume":"101","author":"Quinn","year":"2021","journal-title":"Physiol. 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