The Tissue‐Engineered Small‐Diameter Artery

The characteristics proposed for an “ideal” tissue-engineered small-diameter artery include the following:1–4 It is biocompatible, that is, nonthrombogenic and nonimmunogenic, and resistant to infection as well (all of which are associated with a confluent nonactivated endothelium). Moreover, it results in an acceptable woundhealing response (without fibrosis). It possesses appropriate mechanical properties, including physiological compliance (viscoelasticity) and, critically, adequate strength, without any propensity for permanent creep that leads to aneurysm. It possesses physiological transport properties, that is, appropriate permeability to solutes and cells. Finally, it exhibits key physiological properties, such as vasoconstriction/ relaxation responses. From a practical standpoint, suturability and simplicity of handling are necessary, and, from a commercial standpoint, it must be fabricated in a process that scales well with quantity and be a product that can be shipped and stored. There are four main approaches currently being investigated, all of which satisfy an apparent preqrequisite to biocompatibilty of a small-diameter graft—that no permanent synthetic materials are used. One approach is acellular, based on implanting decellularized tissues treated to enhance biocompatibility, strength, and cell adhesion/invasion leading to cellularization with host cells.5 The other three approaches involve implantation of constructs possessing some degree of cellularity. The most recent of these is based on the concept of self-assembly, wherein cells are cultured on tissue culture plastic in medium inducing high ECM synthesis.6,7 This leads to sheets of neotissue that are subsequently processed into multilayer tubular form. The other two approaches rely on a polymeric scaffold. One is based on forming a tube of a synthetic biodegradable polymer and then seeding the cells (which would not survive the conditions of polymer synthesis), relying on active cell invasion or an applied force to achieve cellularity.8–11 The other is based on a tube of a biopolymer, typically a reconstituted type I collagen gel,12,13 formed with and compacted by tissue cells, where an appropriately applied mechanical constraint to the compaction yields circumferential alignment of fibrils and cells characteristic of the arterial media.14–16 It is this last feature that is most attractive about a biopolymer-based tissue-