Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA.
Department of Plastic Surgery, Clínica Las Américas, Antioquia, Dg. 75B ##2A-80/140, Medellín, Colombia.
Acta Biomater. 2021 Oct 15;134:144-159. doi: 10.1016/j.actbio.2021.06.034. Epub 2021 Jun 27.
Diseases of small diameter blood vessels encompass the largest portion of cardiovascular diseases, with over 4.2 million people undergoing autologous vascular grafting every year. However, approximately one third of patients are ineligible for autologous vascular grafting due to lack of suitable donor vasculature. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissue have potential to serve as ideal biomaterials for production of off-the-shelf vascular grafts capable of eliminating the need for autologous vessel harvest. A modified antigen removal (AR) tissue process, employing aminosulfabetaine-16 (ASB-16) was used to create off-the-shelf small diameter (< 3 mm) vascular graft from bovine saphenous vein ECM scaffolds with significantly reduced antigenic content, while retaining native vascular ECM protein structure and function. Elimination of native tissue antigen content conferred graft-specific adaptive immune avoidance, while retention of native ECM protein macromolecular structure resulted in pro-regenerative cellular infiltration, ECM turnover and innate immune self-recognition in a rabbit subpannicular model. Finally, retention of the delicate vascular basement membrane protein integrity conferred endothelial cell repopulation and 100% patency rate in a rabbit jugular interposition model, comparable only to Autograft implants. Alternatively, the lack of these important basement membrane proteins in otherwise identical scaffolds yielded a patency rate of only 20%. We conclude that acellular antigen removed bovine saphenous vein ECM scaffolds have potential to serve as ideal off-the-shelf small diameter vascular scaffolds with high in vivo patency rates due to their low antigen content, retained native tissue basement membrane integrity and preserved native ECM structure, composition and functional properties. STATEMENT OF SIGNIFICANCE: The use of autologous vessels for the treatment of small diameter vascular diseases is common practice. However, the use of autologous tissue poses significant complications due to tissue harvest and limited availability. Developing an alternative vessel for use for the treatment of small diameter vessel diseases can potentially increase the success rate of autologous vascular grafting by eliminating complications related to the use of autologous vessel and increased availability. This manuscript demonstrates the potential of non-antigenic extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissue as off-the-shelf vascular grafts for the treatment of small diameter vascular diseases.
小直径血管疾病涵盖了心血管疾病的最大部分，每年有超过 420 万人接受自体血管移植。然而，由于缺乏合适的供体血管，大约三分之一的患者不适合自体血管移植。源自异种血管组织的去细胞细胞外基质（ECM）支架具有作为理想生物材料的潜力，可生产现成的血管移植物，从而消除对自体血管采集的需求。一种改良的抗原去除（AR）组织处理方法，使用氨基磺酸盐-16（ASB-16），从牛大隐静脉 ECM 支架中创建小直径（<3mm）现成血管移植物，其抗原含量显著降低，同时保留了天然血管 ECM 蛋白结构和功能。消除天然组织抗原含量赋予移植物特异性适应性免疫回避，而保留天然 ECM 蛋白大分子结构导致在兔亚皮模型中产生促再生细胞浸润、ECM 转化和固有免疫自我识别。最后，保留精细的血管基底膜蛋白完整性赋予内皮细胞再殖和在兔颈内静脉置换模型中的 100%通畅率，仅与自体移植物植入物相当。或者，在其他方面相同的支架中缺乏这些重要的基底膜蛋白会导致通畅率仅为 20%。我们得出结论，去细胞抗原去除的牛大隐静脉 ECM 支架具有作为理想的现成小直径血管支架的潜力，由于其抗原含量低、保留天然组织基底膜完整性和保留天然 ECM 结构、组成和功能特性，具有高体内通畅率。
使用自体血管治疗小直径血管疾病是常见做法。然而，由于组织采集和可用性有限，使用自体组织会带来重大并发症。开发用于治疗小直径血管疾病的替代血管可以通过消除与使用自体血管相关的并发症和增加可用性来提高自体血管移植的成功率。本文证明了源自异种血管组织的非抗原性细胞外基质（ECM）支架作为小直径血管疾病治疗的现成血管移植物的潜力。
