Production and characterization of threads and textiles made from cell-assembled extracellular matrix: Translation...

We previously developed a human and completely biological Tissue-Engineered Vascular Graft (TEVG) to overcome synthetic material limitations. Using a textile-inspired assembly method, TEVGs were woven from threads of Cell-Assembled extracellular Matrix (CAM) produced by cutting CAM sheets obtained after long-term cultures of human skin fibroblasts. The goal of this study was to produce and characterize threads and woven TEVGs made from ovine CAM in order to make possible pre-clinical evaluations of this new type of grafts in an immunocompetent large animal model. In specific culture conditions, ovine CAM sheets had similar strength and composition to those of human sheets. Ovine thread mechanical properties could be controlled by changing different parameters (width, twisting degree, and multifilament assembly). For example, strain at break of CAM ribbons was 23 ± 2 %, while twisted ribbons display values of up to 108 ± 18 %. Similarly, UTS was increased by up to 2.3-times by twisting. Multifilaments displayed a better resistance to needle damage. After 1-month, subcutaneous implantation of allogeneic ovine CAM threads showed a mild inflammatory reaction compared to polypropylene and, especially, decellularized human CAM threads, confirming the need for an allogeneic animal model. Nonetheless, the force at break of CAM ribbons was significantly decreased (2.2 ± 0.5 N vs. 1.1 ± 0.6 N) after 1-month. Finally, ovine CAM-based woven TEVGs (I.D.: 4.3 mm) displayed supraphysiological strength (burst: 4261 ± 1157 mmHg, suture retention: 888 ± 141 gf) and low transmural water permeability (27 ± 16 ml•min^-1•cm^-2) supporting implantation studies in the arterial circulation. STATEMENT OF SIGNIFICANCE: Synthetic vascular grafts perform poorly in small diameter applications. As replacements, we produced completely biological Tissue-Engineered Vascular Grafts (TEVGs) woven from threads of human Cell-Assembled extracellular Matrix (CAM). Here, we develop a large-animal model to perform allogeneic CAM implantation studies to mimic our clinical strategy. Ovine CAM threads were produced with properties similar to their human counterparts. Subcutaneous implantation of the ovine threads revealed a mild immune response compared to synthetic and, more notably, to xenogeneic decellularized human CAM threads. These results support the need for an allogeneic animal model and will allow implantation of TEVGs in the arterial circulation. Overall, this study established the ovine model as a viable large animal model for more clinically relevant CAM-based research.