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Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long\u2010term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone\/poly (<jats:sc>l<\/jats:sc>\u2010lactic acid)\u2013gelatin\u2013A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein\u2010derived peptides (A5G81) to the surface of polydioxanone and poly (<jats:sc>l<\/jats:sc>\u2010lactic acid) fibers. The polymer microfiber\u2013biomacromolecule\u2013peptide frame with biophysical and biochemical cues could orchestrate the biomaterial\u2013host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti\u2010inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell\u2013biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell\u2013material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.<\/jats:p>","DOI":"10.1002\/advs.202305967","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:22:19Z","timestamp":1700587339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biodegradable Cardiac Occluder with Surface Modification by Gelatin\u2013Peptide Conjugate to Promote Endogenous Tissue Regeneration"],"prefix":"10.1002","volume":"11","author":[{"given":"Pengxu","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Structural Heart Disease National Center for Cardiovascular Disease China &amp; State Key Laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine National Clinical Research Center for Cardiovascular Diseases  Beijing 100037 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College  Tianjin 300192 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zefu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Structural Heart Disease National Center for Cardiovascular Disease China &amp; 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