eprintid: 10140322 rev_number: 16 eprint_status: archive userid: 608 dir: disk0/10/14/03/22 datestamp: 2021-12-14 15:55:04 lastmod: 2021-12-20 00:17:59 status_changed: 2021-12-14 15:55:04 type: article metadata_visibility: show creators_name: McGregor, C creators_name: Salmonsmith, J creators_name: Burriesci, G creators_name: Byrne, G title: Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep ispublished: pub divisions: UCL divisions: B02 divisions: D14 divisions: GA2 divisions: B04 divisions: C05 divisions: F45 keywords: Science & Technology, Life Sciences & Biomedicine, Technology, Cardiac & Cardiovascular Systems, Engineering, Biomedical, Cardiovascular System & Cardiology, Engineering, Biological heart valve, Xenogeneic antigens, Gal knockout, Tissue equivalency, BIOPROSTHETIC HEART-VALVE, IMMUNE-RESPONSE, ALPHA-GAL, HEMODYNAMIC PERFORMANCE, AORTIC-VALVE, CALCIFICATION, XENOGRAFT, TECHNOLOGY note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. abstract: Objective There is growing interest in the application of genetically engineered reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves (BHVs) to reduce antibody induced tissue calcification and accelerated structural valve degeneration (SVD). This study tested biological equivalence of valves made from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral valve implantation in sheep. Methods GalKO (n = 5) and standard (n = 5) porcine pericardial BHVs were implanted in a randomized and blind fashion into sheep for 90-days. Valve haemodynamic function was measured at 30-day intervals. After explantation, valves were examined for pannus, vegetation, inflammation, thrombus, and tissue calcification. Results Nine of 10 recipients completed the study. There was no difference between study groups for haemodynamic performance and no adverse valve-related events. Explanted BHVs showed mild pannus integration and minimal thrombus, with no difference between the groups. Limited focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis detected tissue calcium levels of 1.0 µg/mg ± 0.2 for GalKO BHVs and 1.9 µg/mg ± 0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. Conclusions This is the first demonstration of biological equivalence between GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic detrimental biological nor functional impact on BHV performance. Commercial adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the clinical disparity between patients producing anti-Gal antibody and BHVs containing the Gal antigen. GalKO BHVs may reduce accelerated tissue calcification and SVD, enhancing patient choices, especially for younger patients. date: 2021-11-24 date_type: published publisher: SPRINGER official_url: https://doi.org/10.1007/s13239-021-00585-0 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1894185 doi: 10.1007/s13239-021-00585-0 lyricists_name: Burriesci, Gaetano lyricists_name: Byrne, Guerard lyricists_name: McGregor, Christopher lyricists_id: GBURR49 lyricists_id: GWBYR57 lyricists_id: CMCGR95 actors_name: Burriesci, Gaetano actors_name: Flynn, Bernadette actors_id: GBURR49 actors_id: BFFLY94 actors_role: owner actors_role: impersonator full_text_status: public publication: Cardiovascular Engineering and Technology pages: 10 citation: McGregor, C; Salmonsmith, J; Burriesci, G; Byrne, G; (2021) Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep. Cardiovascular Engineering and Technology 10.1007/s13239-021-00585-0 <https://doi.org/10.1007/s13239-021-00585-0>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10140322/1/McGregor2021_Article_BiologicalEquivalenceOfGGTA-1G.pdf