A completely biological tissue‐engineered human blood vessel

Abstract

Mechanically challenged tissue-engineered organs, such as blood vessels, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclusively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular support to produce the media of the vessel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV featured a well-defined, three-layered organization and numerous extracellular matrix proteins, including elastin. In this environment, SMC reexpressed desmin, a differentiation marker known to be lost under standard culture conditions. The endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI 2 , and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to display a burst strength comparable to that of human vessels. Short-term grafting experiment in a canine model demonstrated good handling and suturability characteristics. Taken together, these results suggest that this novel technique can produce completely biological vessels fulfilling the fundamental requirements for grafting: high

In Vitro Biofabrication of Tissues and Organs

“…Good clinical results were obtained when cell sheetÀbased scaffold-free blood vessels were used for the facilitation of hemodialysis (HD) treatment [12,58]. These vessels were fabricated by wrapping a dehydrated fibroblast sheet around a polytetrafluoroethylene (PTFE) tube cylinder and then overlaying a living smooth muscle cell sheet and an outer fibroblast sheet.…”

“…Various approaches have been used to fabricate larger 3D tissues and organs from cell sheets. One example is the "Origami" approach, where, like L'Heureux et al [12], sheets are formed around a temporary 3D scaffold (like surgical tubing). Another standard approach is the layering of multiple cell sheets.…”

“…After the study of the mouse with the human ear, many researchers attempted to create tissues or organs in vitro by constructing scaffolds composed of various biocompatible materials, such as animal-derived collagen [3], synthetic polymers [4], artificially synthesized bone substitutes (calcium-phosphate cement) [5], and autologous fibrin glue [6]. These scaffolds were seeded with a large array of somatic cells or stem cells to reconstruct target tissues such as skin [7], bladder [8], articular cartilage [9], liver [10], bone [11], vascular vessels [12], and even a finger [13].…”

Cell Seeding on UV‐C‐Treated 3D Polymeric Templates Allows for Cost‐Effective Production of Small‐Caliber Tissue‐Engineered Blood Vessels

“…[3] The cell-synthesized ECM method uses the capability of fibroblast and smooth muscle cells (SMCs) to secrete and assemble its own ECM in the presence of ascorbic acid to generate an engineered tissue prior to implantation. [4,5] Furthermore, as it can be directly derived from the patient's own cells without the incorporation of exogenous materials, cellsynthesized ECM tissue-engineered vessels can be integrated into the host without being rejected, degraded, or encapsulated. [6,7] Although this technique presents valuable advantages, it also has some limitations.…”

“…[6,7] Although this technique presents valuable advantages, it also has some limitations. It is a time consuming technique that requires many weeks of tissue culture in order to produce an implantable vessel (between 6 and 20 weeks depending on the final application [5,8,9] ). This approach is currently dependent on the production of flat tissue sheets that then require further rolling manipulation and maturation steps to obtain a solid tubular shape.…”