A novel totally biodegradable device for effective atrial septal defect closure: A 2-year study in sheep.

OBJECTIVE: To evaluate the feasibility, efficacy, and safety of a fully biodegradable poly lactic acid (PLA)-based occluder for atrial septal defect (ASD) closure in an animal model. METHODS: ASDs, approximately 12-mm in diameter, were generated in sheep (n = 18) by needle puncture and balloon dilatation. For ASD closure, occluders were implanted by percutaneous transcatheter approach under echocardiographic guidance. Outcomes were evaluated by transthoracic echocardiography, electrocardiography, blood testing, and histology within the follow-up period ranging from 1 month to 2 years. RESULTS: All occluders were successfully implanted. During follow-up, no animal died; rectal temperatures, blood test results, and electrocardiograms were within normal ranges; and transthoracic echocardiograms, macroscopic studies, and histopathological and electron microscopic examination demonstrated that the occluders were well positioned, with no shifting, residual shunts, severe inflammation, thrombus formation, atrioventricular valve insufficiency, cardiac erosion or arrhythmias. The occluders gradually embedded into the endocardial tissue of the hosts with complete endothelialization and disk absorption at 12 months, and a distinct molecular weight decrease of the framework (to 9% of initial) at 24 months after implantation. CONCLUSIONS: In a sheep model, the use of totally biodegradable occluders appears feasible, efficacious and safe for ASD closure. Studies in humans are ongoing.

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

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.