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Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device

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Abstract

To date, there has been limited investigation of bioabsorbable atrial septal defect (ASD) or patent foramen ovale (PFO) closure devices using clinically relevant large animal models. The purpose of this study is to explore the function and safety of a bioabsorbable ASD occluder (BAO) system for PFO and/or secundum ASD transcatheter closure. Using a sheep model, the intra-atrial septum was evaluated by intracardiac echo (ICE). If a PFO was not present, atrial communication was created via transseptal puncture. Device implantation across the intra-atrial communication was performed with fluoroscopic and ICE guidance. Our 1st generation device consisted of a main structure of thin Poly(l-lactide-co-epsilon-caprolactone) (PLCL) fibers, and an internal Poly glycolic acid (PGA) fabric. Four procedures validated procedure feasibility. Subsequently, device design was modified for improved transcatheter delivery. The 2nd generation device has a two-layered structure and was implanted in six sheep. Results showed procedural success in 9/10 (90%) animals. With deployment, the 1st generation device did not reform into its original disk shape and did not conform nicely along the atrial septum. The 2nd generation device was implanted in six animals, 3 out of 6 survived out to 1 year. At 1 year post implantation, ICE confirmed no residual shunting. By necropsy, biomaterials had partially degraded, and histology of explanted samples revealed significant device endothelialization and biomaterial replacement with a collagen layer. Our results demonstrate that our modified 2nd generation BAO can be deployed via minimally invasive percutaneous transcatheter techniques. The BAO partially degrades over 1 year and is replaced by host native tissues. Future studies are needed prior to clinical trials.

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Acknowledgements

This research is supported by GUNZE Co ltd and The Intramural Heart Center Grant of Nationwide Children’s Specifically, GUNZE Co., Ltd (Saki Okumura M.S, et al.) provided material support through the creation of the Bioabsorbable ASD device. Jason Swinning RT(R) (CI), RCIS as a radiologist was a tremendous contributor to the establishment of this animal model. YM was supported by Department of Defense (DoD) and Funding award from Uehara Memorial Foundation (Tokyo Japan) in 2019. HK was supported by Health Labour Sciences Research Grant and AMED under Grant Number JP15hk0102006. The specific roles of these authors are articulated in the 'author contributions' section.

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  1. Yuichi Matsuzaki and Darren P. Berman are co-first authors.

Authors and Affiliations

  1. Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Yuichi Matsuzaki, Darren P. Berman, Hirotsugu Kurobe, John M. Kelly, Ryuma Iwaki, Kevin Blum, Shoji Toshihiro, John P. Cheatham & Toshiharu Shinoka

  2. Department of Cardiology, The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA

    Darren P. Berman, John M. Kelly, Andrew Harrison & John P. Cheatham

  3. Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, 700 Children’s Drive, T2294, Columbus, OH, 43205, USA

    Toshiharu Shinoka

  4. Department of Cardiovascular Surgery, Ehime University School of Medicine, Touon-shi, Ehime, Japan

    Hirotsugu Kurobe

  5. Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA

    Kevin Blum

  6. Department of Surgery, Cardiovascular Tissue Engineering Program, Ohio State University, Columbus, OH, USA

    Toshiharu Shinoka

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  1. Yuichi Matsuzaki
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Correspondence to Toshiharu Shinoka.

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Conflict of interest

The authors have read the journal's policy and the authors of the manuscript have the following competing interests: TS has received grant support from Gunze Ltd. No authors received salary support from Gunze Ltd. This does not alter our adherence to Pediatric Cardiology policies on sharing data and materials. There are no patents, products in development, or marketed products to declare.

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Supplement 1: Intra Cardiac Echo imaging. ICE images above reveal the created PFO (a) and no residual shunting following placement of the device (b,c) (atrial disks outlined in red). Supplement 2: In vitro hydrolysis study of 1st and 2nd generation ASD devices. The ASD devices were immersed in PBS solution and the mass of the excised samples were compared to Day 0. (a) 1st generation device, (b) 2nd generation device. Supplement 3: Surgical ASD model under cardio-pulmonary bypass was performed on 4 lambs. After making the ASD, our biodegradable devices were implanted as ASD occludesr. There were no deaths in the acute and chronic phases after surgery. Supplement 4 (a) Image of the modified 1st generation ASD device at 1 year timepoint. (b) Fluoro image of modified 1st generation device at 1 year timepoint. (c )Histological evaluation of modified 1st generation ASD device. The red scale bar is 2000μm. 5x magnification. (d) Immunohistochemistry against SMA, vWF, CD68. The scale bar is 200 μm. 10x maginification. Supplement 5: Histology of lungs and brains of sheep implanted with ASD device (1 year timepoint).There was no evidence of infarction by histological analysis. The scale bar is 200 μm. 5x magnification.

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Matsuzaki, Y., Berman, D.P., Kurobe, H. et al. Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device. Pediatr Cardiol 43, 986–994 (2022). https://doi.org/10.1007/s00246-021-02809-5

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  • DOI: https://doi.org/10.1007/s00246-021-02809-5

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