Cardiovascular tissue engineering: state of the artIngenierie tissulaire appliqué aux vaisseaux sanguins : état de l'art
Introduction
Coronary and peripheral vascular bypass grafting is now performed in more than 1 million cases annually in the United States and Europe. Nevertheless, it is not without significant constraints or complications [1], [2], [3], [4], [5], for instance, vein graft disease [6]. Autogenous saphenous or an arm vein is the current material of choice for use as a bypass graft in infrainguinal arterial reconstruction for peripheral bypass procedure while autologous vessels such as the internal mammary artery and the long saphenous vein are used in cardiac bypass procedures. Some patients undergo bypass with prosthetic grafts because no suitable vessel is available, due to previous operations where it has been already used, this class of patient being termed redo, or the remaining vessels are of poor quality. Unfortunately, replacement of arteries with purely synthetic polymeric conduits often leads to the failure of such grafts. This is accentuated in small diameter (less than 6 mm) grafts or in areas of low-flow. This is especially evident in below knee vascular prostheses or in coronary artery bypass grafts (CABG), where very high-flow rates are essential. This is due to the thrombogenicity of the internal surface of the graft and the formation and growth of intimal hyperplasia (IH) [7] around the anastomoses. The latter is mainly due to compliance mismatch between the relatively non-elastic graft and the native viscoelastic blood vessel, and the damage to the endothelium by the sutures of the anastomosis.
The principal polymeric graft materials used in peripheral vascular reconstructions are woven polyethylene terephtalate (Dacron) and expanded polytetrafluoroethylene (ePTFE) while cardiac surgeons use ePTFE graft though reluctantly in some centres. The poor mechanical characteristics of such polymeric materials in term of its size and compliance are significant factors which contribute to their poor patency [8], [9].
The other important factor implicated in graft failure is the lack of endothelial cells (ECs) lining the lumen of the graft [10]. This endothelial monolayer that lines the normal blood vessel serves as a bioregulator of cardiovascular physiology, a part of Virchow’s triad [11]. The endothelium provides structural integrity to the blood vessel by forming a continuous selectively permeable, thromboresistant barrier between circulating blood and the arterial wall. It also controls blood flow and vessel tone [12], platelet activation, adhesion and aggregation [13], leukocyte adhesion [14] and smooth muscle cell (SMC) migration and proliferation [15]. This is the key rationale behind utilising autologous EC to make a haemocompatible artificial polymeric surface that will perform the major functions of an intact healthy endothelium that would normally be found in the blood vessel itself.
The in vitro process of lining ECs to the lumen of the graft is known as ‘seeding’ [16], [17], [18]. To be successful, seeding of grafts has required culturing of ECs over a period of weeks to date. As a result of this problem, there have been numerous attempts at creating fully tissue-engineered vessels composed of prosthetic (ePTFE, Dacron or polyurethane), bioresorable (e.g. PGA, PLLA) or fully biological materials together with autologous cells, which can be readily available on the shelf of any operating theatre [19].
The principal goal of this review is to highlight the current clinical perspectives in the development of a biomimetic vascular substitute that possesses both the mechanical and functional qualities required by both cardiothoracic and vascular surgeons for bypass surgery. Specifically, we seek to emphasise the recent advances that have taken place in cell seeding as well as tissue engineering of the current generation of prosthetic grafts.
Section snippets
Search methods
All the papers were identified by PubMed and CAS searches between years 1966 and 2004 with the following keywords: Endothelium, Tissue-Engineering, Coronary bypass grafts, Vascular bypass grafts, Seeding, Mesothelium, Cardiovascular, Prosthetic graft, Biological tissue-engineered vascular grafts, Tissue-engineered vascular grafts, Biological vascular grafts, Endothelial progenitor cells (EPCs).
The need for tissue engineering of prosthetic grafts
The ideal cardiovascular bypass graft must have the following qualities: durability, resistance to degradation, non-toxicity, resistance to infection and availability in a variety of sizes which suits a wide range of cardiac and peripheral vascular reconstructions [20]. In addition, the implant should have good handling characteristics, be flexible, easy to suture and result in minimal needle-hole and interstitial bleeding following implantation. For long-term use, the prosthesis must generate
Discussion
Due to the poor patency rate of traditional prosthetic grafts that is primarily due to low compliance and thrombogenicity, seeding and tissue engineering are being used to achieve an internal environment similar to that found in native vessels. The initial experiments trying to use a single-stage seeding in animals showed good results. However when this was tried in humans the results was poor. It was then realised that animals will spontaneously endothelialise any graft even if not seeded thus
Acknowledgments
We acknowledge Dr. Philippe Fernandez and Dr. Murielle Remy-Zolghadri for their useful comments and suggestion in the manuscript. This work supported in part by UCL BioMedica Plc, London, UK and Nervation Ltd., UK who provided a grant to develop bypass graft.
References (191)
- et al.
Lower extremity arterial reconstruction in the very elderly: successful outcome preserves not only the limb but also residential status and ambulatory function
J. Vasc. Surg.
(1998) - et al.
Arterialization in coronary artery surgery in Japan and Hong Kong
Semin. Thorac. Cardiovasc. Surg.
(2002) - et al.
Development of intimal hyperplasia in six different vascular prostheses
Eur. J. Vasc. Endovasc. Surg.
(2000) - et al.
Effect of compliance mismatch on vascular graft patency
J. Vasc. Surg.
(1987) - et al.
Endothelial cell seeding of polytetrafluoroethylene vascular grafts in humans: a preliminary report
J. Vasc. Surg.
(1987) - et al.
Advances in vascular tissue engineering
Cardiovasc. Pathol.
(2003) - et al.
Polyurethane vascular prostheses decreases neointimal formation compared with expanded polytetrafluoroethylene
J. Vasc. Surg.
(1999) - et al.
Optimal endothelialisation of a new compliant poly(carbonate-urea)urethane vascular graft with effect of physiological shear stress
Eur. J. Vasc. Endovasc. Surg.
(2000) - et al.
New prostheses for use in bypass grafts with special emphasis on polyurethanes
Cardiovasc. Surg.
(2002) - et al.
ESCA surface characterization of four IUPAC reference polymers
Biomaterials
(1993)