New Developments in Tissue Engineering of Microvascular Prostheses

Abstract

Clinical needs to have a ready-to-use small-diameter vascular prostheses are very remarkable and cover different fields of surgery: plastic and reconstructive surgery (microvascular transfer of free flaps), heart surgery (treatment of ischemic heart diseases), vascular surgery (distal revascularization of lower limbs), neurosurgery (substitution of intracranial arteries), paediatric vascular surgery. In particular, there is a substantial need for tissue-engineered, living, autologous replacement materials with the potential for growth in paediatric applications and for substitute small diameter vessel that up to now are defined the “holy grail” of vascular biology. Completely bio-resorbable vascular prostheses with the capacity for induce regeneration and growth of a new vascular segment may overcome the limitations of contemporary artificial prostheses that are nonviable, artificial, or allogenic materials lacking the capacity of growth, repair, and remodelling. These intrinsic properties limit their long-term function, posing the substantial burden of graft failure and related re-operations, particularly on paediatric patient population. Moreover, these synthetic materials are not suitable for the reconstruction of the coronary, carotid, or femoral arteries as well as other small diameter vessels (< 6 mm). Autologous native vessels, i.e., the saphenous vein and mammary artery, are the most currently used material for small-diameter arterial replacement. Immune acceptance is a major advantage offered by this technique of “ready to use” conduits. However, the availability of suitable native replacements is limited when multiple conduits are required, especially in patients with diffuse vascular disease. The need for a prosthetic graft that performs as a small diameter conduit has led investigators to pursue many avenues in vascular biology (Figure 1). There are four main approaches currently being investigated, all of which satisfy an apparent prerequisite 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. 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. 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