Pellenc Quentin, Touma Joseph, Coscas Raphael, Edorh Grégoire, Pereira Maria, Karp Jeffrey, Castier Yves, Desgranges Pascal, Alsac Jean Marc
Department of Vascular and Thoracic Surgery, Bichat University Hospital, AP-HP, Paris, France -
Paris-Diderot Paris VII University, Paris, France -
J Cardiovasc Surg (Torino). 2019 Oct;60(5):599-611. doi: 10.23736/S0021-9509.19.10783-5. Epub 2019 May 10.
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.
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.
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.
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.
合成血管材料的使用，尤其是基于聚四氟乙烯（PTFE）的材料，可能与出血相关，这可能会增加手术时间和失血量。现有的旨在确保止血的商业密封剂均未兼具生物可吸收性、高粘度、疏水性、与底层组织的顺应性以及按需激活的特性。
设计了一项研究，在三项关于开放性颈动脉和主动脉血管手术的大型动物研究中，评估一种新型合成的按需光激活的基于聚（甘油癸二酸酯）丙烯酸酯（PGSA）的SETALIUM™血管密封剂（法国巴黎的TISSIUM公司生产）的生物相容性、体内性能和生物可吸收性。然后，在前瞻性单臂多中心研究中，将临床前结果转化到临床环境中，该研究针对需要使用ePTFE补片进行颈动脉内膜切除术的患者。
生物相容性测试表明，基于PGSA的SETALIUM™血管密封剂在标准临床剂量下以及高达预期临床剂量40倍的剂量下，均未引发任何显著的毒性反应。基于PGSA的密封剂显示出无热原性、无致敏性、无刺激性、无染色体断裂性且无致突变性。动物研究显示出优异的性能和安全性结果，在颈动脉和主动脉研究中，100%的动物实现了具有临床意义的止血，且局部耐受性良好。组织病理学和形态计量学分析表明，基于PGSA的密封剂在12个月时表面逐渐且持续地生物吸收，吸收率高达86%。在临床研究中，基于PGSA的密封剂应用效果良好且安全，84%的病例实现了即时止血，在为期一年的随访中未报告与密封剂相关的不良事件。
我们研究中所探究的新型合成按需光激活的基于PGSA的SETALIUM™血管密封剂在动物研究中显示出良好的生物相容性、持续且逐渐的表面生物吸收性以及可接受的安全性。此外，首次人体使用表明，该密封剂是在颈动脉血管重建中实现快速且可控止血的安全有效替代方案。一项更大规模的随机对照研究将进一步验证这些令人鼓舞的初步结果。
