Patency and in vivo compatibility of bacterial nanocellulose grafts as small-diameter vascular substitute

Abstract

Objective: Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential. The aim was to investigate mechanical characteristics of modified second-generation BNC tubes, to evaluate in vivo performance and biocompatibility, and to analyze patency rates.Methods: We replaced the right carotid artery of 23 sheep with second-generation BNC tubes. Compared with our firstgeneration tubes, tubes were modified with different surface properties and diminished wall thickness (inner diameter, 4.0-5.0 mm; wall thickness, 1.0-2.5 mm; length, 100 mm) to generate a smoother inner surface with reduced thrombogenic potential and a more porous outer zone, allowing easier cell immigration.Results: At the end of the investigational period, BNC tubes were explanted and grafts were processed for histopathologic analysis. Histologic analysis revealed no acute signs of foreign body reaction such as immigration of giant cells or other acute inflammatory reaction and therefore provided evidence for good biocompatibility of the second-generation tubes. However, all grafts of the sheep without antiplatelet therapy were occluded after 9 months, whereas grafts in sheep receiving dual platelet inhibition showed a patency rate of 67% (six of nine grafts). Further modified grafts revealed a patency rate of 80% (four of five grafts remained open).Conclusions: Patency rates of the second-generation tubes could be substantially improved compared with our firstgeneration tubes. However, poor patency rates of tissue-engineered blood vessels still limit their use in clinical studies. Further efforts in terms of in vitro and in vivo studies are essential to improve grafts of BNC.

Latest Advances on Bacterial Cellulose‐Based Materials for Wound Healing, Delivery Systems, and Tissue Engineering

“…These techniques can be as simple as piercing BC with a metallic skewer with the right diameter and use it as a mold or cultivating the BC inside a double‐cylinder bioreactor . More elaborated techniques were also reported, such as cultivating BC layer‐by‐layer around a guide bar or preparing a self‐rolling BC membrane with shape memory …”

“…In another study, where the BC graft was produced layer‐by‐layer, the aim was to prepare a graft with a smoother and compacter inner wall than a graft where the morphology of the inner wall was not controlled. Results showed increased patency from 67% to 80% in 9‐month period, while an antiplatelet drug was being orally administrated to the animals.…”

Applications of bacterial-synthesized cellulose in veterinary medicine – a review

“…Recent studies have investigated the use of BC for the regeneration of cardiovascular (Mohammadi 2011;Weber et al 2018), nervous (Kowalska-Ludwicka et al 2013;Zhu et al 2014), urinary tissue (Huang et al 2015;L v et al 2015). Bacterial cellulose was tested as wound dressing material (Mohamad et al 2014;Qiu et al 2016); artificial skin (Kwak et al 2015); artificial blood vessels (Scherner et al 2014); other biomedical devices because of its specific properties such as: the 3D nanomeric structures; unique physical, mechanical, and thermal properties; and its higher purity (Mohite et al 2019).…”

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“…These tubes were also considered to have great potential for substituting other hollow organs, including the ureter and the esophagus [175]. In a study by Weber et al [176], BNC tubes were used to replace the right carotid artery in sheep in vivo. After explantation, a histologic analysis revealed no acute signs of foreign body reaction, such as immigration of giant cells or some other acute inflammatory reaction, and therefore provided evidence for good biocompatibility of the tubes.…”

“…However, the tubes were highly prone to thrombotic occlusion, and their implantation required antiplatelet therapy [176]. Another interesting idea was to use bacterial nanocellulose coupled with superparamagnetic iron oxide nanoparticles for coating endovascular stents, which will then attract vascular smooth muscle cells (VSMCs) for in situ reconstruction of the tunica media in blood vessels.…”