Small-diameter bacterial cellulose-based vascular grafts for coronary artery bypass grafting in a pig model

Abstract

Surgical revascularization is the gold standard in most cases of complex coronary artery disease. For coronary artery bypass grafting, autologous grafts are state-of-the-art due to their long-term patency. A non-negligible amount of patients lack suitable bypass material as a result of concomitant diseases or previous interventions. As a promising alternative, tissue-engineered vascular grafts made of biomaterials such as bacterial cellulose (BC) are gaining more and more attention. However, the production of small-diameter grafts (inner diameter < 6 mm) of application-oriented length (> 5 cm) and their in vivo long-term patency remain challenging. In this study, grafts of 20 cm in length with an inner diameter of 3 mm were generated in a custom-made bioreactor. To potentially improve graft compliance and, therefore in vivo patency, BC was combined with an embedded cobalt–chromium mesh. The grafts were designed for in vivo endothelialization and specific surgical properties and implanted as an aortocoronary bypass in a left anterior descending occluded pig model (n = 8). Coronary angiography showed complete patency postoperatively at 4 weeks. Following 4 weeks in vivo, the grafts were explanted revealing a three-layered wall structure. Grafts were colonized by smooth muscle cells and a luminal layer of endothelial cells with early formation of vasa privata indicating functional remodeling. These encouraging findings in a large animal model reveal the great potential of small-diameter BC grafts for coronary and peripheral bypass grafting.

Bacterial-Nanocellulose-Based Biointerfaces and Biomimetic Constructs for Blood-Contacting Medical Applications

“…The synthesized tubes were tested in a large animal model, and after 4 weeks, the tubes were completely endothelialized in vivo and compete patency was observed. 131 4.2.3. Static Fermentation Methods of Producing Tubular BNC.…”

“…Fundamental research has revealed that BNC-based vascular grafts possess unique properties that make them attractive alternatives to existing synthetic grafts. BNC-based vascular grafts have been shown to exhibit outstanding biocompatibility, high-burst pressure, nanofibril-like structures, thermal stability, and desired surgical manageability. ,, Moreover, BNC-based vascular grafts have been found to integrate well with the surrounding tissue and host arteries, promoting vascular remodeling by endothelial cells and SMCs . The high-water-retention capabilities of BNC and the hydration layer formed around it result in increased hemocompatibility and limit the activation of the blood coagulation system. , Thrombin generation has been found to be significantly less on BNC vascular grafts than commercially used PET and ePTFE grafts .…”

Bacterial Cellulose-Based Materials: A Perspective on Cardiovascular Tissue Engineering Applications

“…The presence of channels in the BC scaffold can facilitate the infiltration of endothelial cells and other cell types, promoting the formation of functional blood vessels. [24][25][26]216 In conclusion, BC is a promising material for cardiovascular TE due to its biocompatibility, mechanical properties, ease of customization, and porous structure. Porous nanomaterials and metal−organic frameworks (MOFs) as highly porous materials with unique chemical and mechanical properties can be deployed in combination with BC for cardiovascular TE.…”

“…The vascular grafts were prepared for endothelialization and specific surgical properties ( in vivo ); they were implanted as an aortocoronary bypass in a left anterior descending occluded pig model, showing great capabilities of small-diameter BC grafts for coronary and peripheral bypass grafting. This BC-vascular graft exhibited the benefits of rapid/simple fabrication process, enough mechanical strength, and satisfactory length for cardiovascular TE purposes; the design of this graft could provide the in vivo endothelialization procedure, avoiding time-consuming preseeding and cell expansion steps …”

“…( E ) The application of BC graft as a coronary bypass (an arrow in direction of flow) after distal anastomosis to the occluded left anterior descending (*) using an elastic band with a tourniquet (•). Reproduced with permission from ref . Copyright 2022 Frontiers.…”