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However, their broader development is often constrained by limited intrinsic functionality and inadequate dynamic responsiveness. Metal complexes offer a promising solution to these limitations by introducing dynamic coordination interactions, catalytic properties, and multi-stimuli responsiveness, enabling new avenues for hydrogel functionalization. This review begins with a systematic examination of four principal strategies for integrating metal complexes into hydrogel matrices: physical embedding, chemical grafting, coordination-based cross-linking, and in situ complex formation. This review methodically compares these four integration strategies rather than treating them as interchangeable routes. Emerging evidence indicates that incorporating metal complexes can endow hydrogels with enhanced biomedical capabilities, including anti-inflammatory, anticancer, and antibacterial activities. Despite these advances, several challenges persist, particularly with respect to biocompatibility, long-term structural and functional stability, and scalable manufacturing. Consequently, we propose the implementation of application-specific design criteria and a translational framework covering metal pharmacokinetics, biodegradation, manufacturing reproducibility, and long-term safety. Future research is therefore expected to focus on the development of biomimetic, multi-responsive hydrogel systems that support precision therapeutics and regenerative medicine. This analysis distinguishes metal-coordinated hydrogels from metal-free hydrogels and unconfined metal nanomaterials, while identifying the evidence still required for clinical development.<\/jats:p>","DOI":"10.1021\/acsomega.6c06631","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:02:01Z","timestamp":1788890521000},"page":"54828-54846","source":"Crossref","is-referenced-by-count":0,"title":["Multifunctional\nMetal-Coordinated Hydrogels: Controlled\nSynthesis and Advances in Anti-Inflammatory, Anticancer, and Antibacterial\nApplications"],"prefix":"10.1021","volume":"11","author":[{"given":"Junjia","family":"Gao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Shenyang Medical College , ,","place":["Shenyang, People\u2019s Republic of China, 110024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng-En","family":"Jin","sequence":"additional","affiliation":[{"name":"Central Hospital Affiliated to Shenyang Medical College , ,","place":["Shenyang, People\u2019s Republic of China, 110024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0774-7224","authenticated-orcid":true,"given":"Yikuan","family":"Li","sequence":"additional","affiliation":[{"name":"Shenyang Medical College , , ,","place":["Shenyang, People\u2019s Republic of China, 110034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Gu","sequence":"additional","affiliation":[{"name":"Northeastern University , , ,","place":["Shenyang, People\u2019s Republic of China, 110819"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhi","sequence":"additional","affiliation":[{"name":"Shenyang Medical College , , ,","place":["Shenyang, People\u2019s Republic of China, 110034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Shenyang Medical College , ,","place":["Shenyang, People\u2019s Republic of China, 110024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenyang Medical College , , ,","place":["Shenyang, People\u2019s Republic of China, 110034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-9546","authenticated-orcid":true,"given":"Sen","family":"Gao","sequence":"additional","affiliation":[{"name":"Shenyang Medical College , , ,","place":["Shenyang, People\u2019s Republic of China, 110034"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026092211025016900_cit1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jare.2022.04.005","article-title":"Polysaccharide-based\nbiopolymer hydrogels for heavy metal detection and adsorption","volume":"44","author":"Zhao","year":"2023","journal-title":"J. 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