ORIGINAL ARTICLE  VASCULAR SECTION 

The Journal of Cardiovascular Surgery 2019 October;60(5):599-611

DOI: 10.23736/S0021-9509.19.10783-5

Copyright © 2019 EDIZIONI MINERVA MEDICA

language: English

Preclinical and clinical evaluation of a novel synthetic bioresorbable, on-demand, light-activated sealant in vascular reconstruction

Quentin PELLENC ^{1, 2} ✉, Joseph TOUMA ³, Raphael COSCAS ^{4, 5}, Grégoire EDORH ⁶, Maria PEREIRA ⁶, Jeffrey KARP ⁷, Yves CASTIER ^{1, 2}, Pascal DESGRANGES ³, Jean Marc ALSAC ^{8, 9, 10}

¹ Department of Vascular and Thoracic Surgery, Bichat University Hospital, AP-HP, Paris, France; ² Paris-Diderot Paris VII University, Paris, France; ³ Department of Vascular Surgery, Henri Mondor University Hospital, AP-HP, Créteil, France; ⁴ Department of Vascular Surgery, Ambroise Paré University Hospital, AP-HP, Boulogne-Billancourt, France; ⁵ Inserm U1018, Epidemiology and Population Health Research Center (CESP), Versailles Saint-Quentin-en-Yvelines University, Federal University of Paris-Saclay, Villejuif, France; ⁶ TISSIUM Biomorphic Programmable Polymers, Paris, France; ⁷ Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; ⁸ Department of Vascular Surgery, Georges Pompidou European University Hospital, AP-HP, Paris, France; ⁹ Paris-Descartes Paris V University, Paris, France; ¹⁰ Inserm UMR 970, Paris Cardiovascular Research Center (PARCC), Paris, France

BACKGROUND: Synthetic vascular material use, particularly polytetrafluoroethylene- (PTFE) -based, can be associated with bleeding, which may increase operative time and blood loss. None of the commercially available sealants designed to ensure hemostasis combine bioresorption, high viscosity, hydrophobicity, and compliance with the underlying tissue and on-demand activation.
METHODS: A study was designed to assess the biocompatibility and in-vivo performance and bioresorption of a new synthetic on-demand light-activated poly(glycerol-sebacate) acrylate- (PGSA) -based SETALIUM™ Vascular Sealant (TISSIUM, Paris, France) in three large animal studies of open vascular carotid and aortic surgery. The pre-clinical results were then translated into a clinical setting in a prospective, single-arm multicenter study in patients requiring carotid endarterectomy using an ePTFE patch.
RESULTS: The biocompatibility testing showed that the PGSA-based SETALIUM™ Vascular Sealant did not induce any significant toxic reaction at a standard clinical dose nor at doses up to 40 times the equivalent intended clinical dose. The PGSA-based sealant was shown to be non-pyrogenic, non-sensitizing, non-irritant, non-clastogenic, and non-mutagenic. The animal studies showed excellent performance and safety results, with clinically significant hemostasis achieved in 100% of the animals in both carotid and aorta studies and excellent local tolerance. Histopathology and morphometric analyses showed surface-based gradual and sustained bioresorption of the PGSA-based sealant up to 86% at 12 months. In the clinical study, the application of the PGSA-based sealant resulted in good performance and safety, with immediate hemostasis achieved in 84% of the cases and no adverse event related to the sealant reported through the one-year follow-up.
CONCLUSIONS: The new synthetic on-demand light activated PGSA-based SETALIUM™ Vascular Sealant investigated in our studies demonstrated good biocompatibility, sustained and gradual surface based bioresorption, and acceptable safety profile in animal studies. In addition, the first in-human use showed that the sealant is a safe and effective alternative to achieve fast and controlled hemostasis in vascular carotid reconstructions. A larger randomized controlled study will allow further validation of these encouraging preliminary results.

KEY WORDS: Polymers; Vascular surgical procedures; Biocompatible materials; Materials testing; Poly(glycerol-sebacate)