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Herein, we developed an aptamer\u2010functionalized dual\u2010network hydrogel platform for the specific enrichment and non\u2010destructive release of exosomes. This study proposes an aptamer\u2010functionalized dual\u2010network hydrogel technology aimed at achieving the specific separation and non\u2010destructive release of exosomes from complex biological samples. Using a sacrificial nickel foam template, polyacrylamide and polyacrylic acid were sequentially polymerized to construct a stable, interconnected macroporous hydrogel framework, which minimized flow resistance for rapid sample permeation. To build the affinity interface, circular DNA templates were chemically crosslinked into the accessible carboxyl groups of the polyacrylic acid segments, followed by in situ rolling circle amplification (RCA) to generate long DNA concatamers rich in repetitive CD63 aptamer sequences for efficient target capture. Meanwhile, polyacrylic acid is expected to reduce the non\u2010specific adsorption of the composite hydrogel toward contaminating proteins, thereby improving the purity of the isolated exosomes. Finally, introducing complementary DNA displacement strands enables efficient, mild vesicle release via competitive hybridization, fully preserving structural integrity and cellular uptake ability. This bio\u2010functionalized hydrogel system provides a gentle, efficient, and reliable methodology for high\u2010purity exosome isolation, offering a promising tool for advanced biomedical applications.<\/jats:p>","DOI":"10.1002\/smtd.71066","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:00:31Z","timestamp":1790856031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficient Separation of Exosomes by Aptamer\u2010Functionalized Polyacrylamide\u2010Polyacrylic Acid Hydrogel"],"prefix":"10.1002","author":[{"given":"Wei","family":"Tan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Synthetic Biology, Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Synthetic Biology and Biomanufacturing Tianjin University  Tianjin P. R. 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