Cell‐assembled Extracellular Matrix (CAM) as a Biomaterial for Building Vascular Grafts

Abstract

Sheets of human CAM, produced by cultured cells in vitro, have been rolled to produce completely biological tissue‐engineered vascular grafts (TEVGs). Despite a rapid and successful progression to clinical trials, this approach remains complex. Our novel strategy is to produce TEVG with yarns produced from CAM sheets using a textile‐based approach. This strategy is faster, more reliable, more versatile and more easily automated. CAM sheets can be cut in ribbons of various widths, which can also be twisted to make threads. Yarn (ribbons or threads) can be processed in different ways: devitalized (freezing/dehydration/freezing/rehydration cycle), decellularized (8 mM CHAPS, 1 M NaCl, 25 mM EDTA, 0.12 M NaOH) and/or gamma‐sterilized (25 kGy). We have evaluated the effect of these processing steps on the histological and mechanical properties of the yarn. We have also assessed the impact of these steps on the remodeling (histological and mechanical) of the yarn after subcutaneous implantation in a nude rat for up to 6 months. Results showed that the human CAM‐based yarn creates very little inflammatory reaction and is essentially only mildly remodeled by the host response. However, some processing steps do lead to increased reactivity and decreased performance in vivo. Woven vessels display remarkable mechanical properties without the need for synthetic scaffolding or chemical crosslinking. An allogeneic large animal model is in development to address remodeling in an allogeneic setting in an immunologically competent recipient. Because it can be produced according to specific mechanical and physical specifications, and because it can be used with standard textile assembly methods, the CAM can truly be called a “bio‐material”. More importantly, because of its native‐like structure, this material has the potential to be accepted by the host without significant immune responses and to support a long‐term “physiological” remodeling process.Support or Funding InformationNational Institute of Health Small Business Innovation Research (SBIR) program (HL105010), the Ministère de la Recherche et de l’Enseignement Supérieur, the Chaire Senior de l’Initiative d’Excellence de l’Université de Bordeaux (IdEx Bordeaux), the Agence Nationale de la Recherche (ANR‐16‐CE18‐0024‐01), the Région Nouvelle Aquitaine (2016‐1R30402), and the European Research Council (Advanced Grant # 785908).A thread and a woven vessel made from human CAM.Figure 1