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Bonding these mechanically dissimilar materials may resolve these limitations, preserve their advantages, and offer new opportunities as biointerfaces. Here, a robust adhesion strategy is proposed to integrate highly entangled tough hydrogels and diverse plastics with high interfacial adhesion energy and strength. Systemic investigations on the effects of hydrogel monomer content and crosslink fraction revealed the significant contributions of both polymer physical entanglements and interfacial covalent bonding. This hybrid engineering strategy also enables the plastic\u2010hydrogel composite to attenuate foreign body response caused by pristine rigid plastics in vivo in mice. This versatile materials engineering approach may be broadly applicable to other polymer\u2010based devices commonly used in regenerative medicine and surgical robotics.<\/jats:p>","DOI":"10.1002\/adhm.202402605","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T23:42:32Z","timestamp":1735170152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integrating Hydrogels and Biomedical Plastics via In Situ Physical Entanglements and Covalent Bonding"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7209-9842","authenticated-orcid":false,"given":"Zhenwei","family":"Ma","sequence":"first","affiliation":[{"name":"John A. 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