Biodegradable Cardiac Occluder with Surface Modification by Gelatin–Peptide Conjugate to Promote Endogenous Tissue Regeneration

• Published in: Advanced science 2024-01, Vol.11 (2), p.e2305967-n/a
• Main Authors: Kong, Pengxu, Liu, Xiang, Li, Zefu, Wang, Jingrong, Gao, Rui, Feng, Shuyi, Li, Hang, Zhang, Fengwen, Feng, Zujian, Huang, Pingsheng, Wang, Shouzheng, Zhuang, Donglin, Ouyang, Wenbin, Wang, Weiwei, Pan, Xiangbin
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Biocompatible Materials; Biodegradable materials; biodegradable polymers; Biomedical materials; Cardiac arrhythmia; Cell adhesion & migration; cell–material interface; congenital heart disease; Endothelial Cells; Gelatin - chemistry; Hydrogels; Lactic Acid; Mechanical properties; Morphology; occluder; Peptides; Polydioxanone; Polymers; Scanning electron microscopy; Septal Occluder Device; Swine; Thoracic surgery; Tissue engineering; tissue regeneration; Transplants & implants
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202305967

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long‐term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l‐lactic acid)–gelatin–A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein‐derived peptides (A5G81) to the surface of polydioxanone and poly (l‐lactic acid) fibers. The polymer microfiber–biomacromolecule–peptide frame with biophysical and biochemical cues could orchestrate the biomaterial–host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti‐inflammatory 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–biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell–material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices. In this study, the surface of the biodegradable cardiac occluder is modified by covalently conjugating biomolecules composed of gelatin and layer adhesive protein‐derived peptides, which promotes in situ tissue regeneration by accelerating surface endothelialization and regulating immune response in a porcine atrial septal defect model.