Regenerative medicine, tissue engineering and vascular surgery: twenty first century clinical challenges

Abstract

Cardiovascular disease remains one of the leading causes ofdeath and illness in man. Currently available vascular pros-thetic devices are associated with significant risks of infec-tion, thromboembolism, degeneration and growth failure,especially in younger patients. Because of such problems,several groups of researchers are seeking to engineer humanorgans and tissues capable of replacing diseased and dam-aged native cardiovascular tissues [1]. Tissue engineering,defined as ‘‘an interdisciplinary field that applies the prin-ciples of engineering and life sciences towards the devel-opment of biological substitutes that restore, maintain, orimprove tissue function’’, offers the possibility of providinga true biological substitute with patient-specific properties[1, 2]. Vascular tissue engineering applies engineeringprinciples and techniques to restore the structure and func-tion of pathologically altered molecules, cells, and tissues ofblood vessels [3]. The major advantage of tissue-engineeredcardio-vascular tissues lies in their ability to grow, remodel,and repair in vivo without rejection. Moreover, such bio-logicaltissue-engineeredsubstitutesprovidepatientswithanalternative source of vascular conduits especially in caseswhere shortage of autologous and diseased veins is a prob-lem. In essence, tissue-engineered cardiovascular devicesoffer the possibility of developing a patient-specificimplantable device with the potential of growing alongsidenative tissue without the risk of rejection [4].The key components for developing processed biologicaltissues are cells, scaffolds, growth factors, hormones andnutrients, and a biologic environment provided by bioreac-tors[4].Severalmethodologiesforconstructingbloodvesselreplacements with biological functionality have emerged.The most common strategies include the use of cell-seededgels, cellself-assembly, cell-seeded biodegradable syntheticscaffolds and xenogeneic acellular materials [5].It has been more than two decades since Weinberg andBell [6] introduced the innovative concept of developing avascular graft from living tissue. Their graft combinedsynthetic and biological components; it was made of col-lagen integrated with Dacron mesh, smooth muscle cellsand a functioning endothelium. Recent advances in cellu-lar, scaffold and bioreactor technologies indicate that thegoal of producing purely tissue-engineered vascular tissueswith no synthetic components is now achievable anddevices may soon be available for clinical use [7, 8].Nevertheless, a number of significant problems remain tobe resolved before biological vascular grafts can be usedroutinely in the management of vascular disease.McAllister and colleagues [9] have recently reported thesuccessful implantation of a completely biologic tissue-engineered graft for vascular access in ten patients with endstage renal disease receiving haemodialysis. Patency rates at1 and 6 months were 78 and 60%, respectively. This is thefirst encouraging result of the use of a tissue-engineeredvascular graft in a clinical setting. McAllister et al. used thecell self-assembly technique (as opposed to cell-seeded gelsor cell scaffold technology) for the construction of theirtissue-engineered vessel. In this approach, first described byL’Heureux in 1998 [10], human tissue-engineered vesselsare constructed by taking advantage of the natural ability of