Elsevier

Pathologie Biologie

Volume 53, Issue 10, December 2005, Pages 599-612
Pathologie Biologie

Cardiovascular tissue engineering: state of the artIngenierie tissulaire appliqué aux vaisseaux sanguins : état de l'art

https://doi.org/10.1016/j.patbio.2004.12.006Get rights and content

Abstract

In patients requiring coronary or peripheral vascular bypass procedures, autogenous arterial or vein grafts remain as the conduit of choice even in the case of redo patients. It is in this class of redo patients that often natural tissue of suitable quality becomes unavailable; so that prosthetic material is then used. Prosthetic grafts are liable to fail due to graft occlusion caused by surface thrombogenicity and lack of elasticity. To prevent this, seeding of the graft lumen with endothelial cells has been undertaken and recent clinical studies have evidenced patency rates approaching reasonable vein grafts. Recent advances have also looked at developing a completely artificial biological graft engineered from the patient’s cells with surface and viscoelastic properties similar to autogenous vessels. This review encompasses both endothelialisation of grafts and the construction of biological cardiovascular conduits.

Résumé

Les veines ou artères autologues restent le matériau de remplacement de choix pour les pontages coronariens ou périphériques, même chez les patients dont l'état de santé necessite une ré-intervention. Cependant, pour ces derniers, l'utilisation d'un tel matériel s'avère souvent impossible et l'implantation d'une prothèse synthétique reste la seule aternative. Les implants synthétiques sont toutefois sujet à l'occlusion en raison de leur caractére thrombogène et de leur manque de compliance. C'est pourquoi des études de recouvrement de leur surface interne par un endothélium vasculaire ont été entreprises, qui aboutissent à des taux de perméabilité avoisinant ceux rapportés pour la veine saphène autologue. Des tentatives de production de vaisseaux biologiques à partir des cellules des patients sont également en cours, lesquelles présenteraient des propriétés visco-élastiques améliorées par rapport à leurs contre-parties synthétiques. Cet article fait le point sur l'endothélialisation des implants synthétiques et des diverses stratégies de fabrication des implants biologiques.

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)

  • J.D. Berglund et al.

    A biological hybrid model for collagen-based tissue engineered vascular constructs

    Biomaterials

    (2003)
  • A. Tiwari et al.

    Improving endothelial cell retention for single stage seeding of prosthetic grafts: use of polymer sequences of arginine-glycine-aspartate

    Eur. J. Vasc. Endovasc. Surg.

    (2003)
  • A. Tiwari et al.

    Tissue engineering of vascular bypass grafts: role of endothelial cell extraction

    Eur. J. Vasc. Endovasc. Surg.

    (2001)
  • P. Zilla et al.

    In situ cannulation, microgrid follow-up and low-density plating provide first passage endothelial cell masscultures for in vitro lining

    J. Vasc. Surg.

    (1990)
  • F. Hess et al.

    Patency and morphology of fibrous polyurethane vascular prostheses implanted in the femoral artery of dogs after seeding with subcultivated endothelial cells

    Eur. J. Vasc. Surg.

    (1993)
  • J.M. Seeger et al.

    Improved endothelial cell seeding with cultured cells and fibronectin-coated grafts

    J. Surg. Res.

    (1985)
  • J.M. Seeger et al.

    Improved in vivo endothelialization of prosthetic grafts by surface modification with fibronectin

    J. Vasc. Surg.

    (1988)
  • O.E. Teebken et al.

    Tissue-engineered bioprosthetic venous valve: a long-term study in sheep

    Eur. J. Vasc. Endovasc. Surg.

    (2003)
  • A. Giudiceandrea et al.

    Effect of prolonged pulsatile shear stress in vitro on endothelial cell seeded PTFE and compliant polyurethane vascular grafts

    Eur. J. Vasc. Endovasc. Surg.

    (1998)
  • M. Herring et al.

    Seeding human arterial prosthesis with mechanically derived endothelium. The detrimental effect of smoking

    J. Vasc. Surg.

    (1984)
  • P. Zilla et al.

    Reduced reproductive capacity of freshly harvested endothelial cells in smokers: a possible shortcoming in the success of seeding

    J. Vasc. Surg.

    (1989)
  • H.R. Laube et al.

    Clinical experience with autologous endothelial cell-seeded polytetrafluoroethylene coronary artery bypass grafts

    J. Thorac. Cardiovasc. Surg.

    (2000)
  • E. Anders et al.

    Microvascular endothelial cells from human omental tissue: modified method for long term cultivation and new aspects of characterisation

    Microvasc. Res.

    (1987)
  • E.C. Douville et al.

    Impact of endothelial cell seeding on long-term patency and subendothelial proliferation in a small-caliber highly porous polytetrafluoroethylene graft

    J. Vasc. Surg.

    (1987)
  • S.T. Rashid et al.

    The use of animal models in developing the discipline of cardiovascular tissue engineering: a review

    Biomaterials

    (2004)
  • S.P. Schmidt et al.

    Endothelial cell-seeded 4 mm Dacron vascular grafts: effects of blood flow manipulation through the grafts

    J. Vasc. Surg.

    (1984)
  • H.J. Verhagen et al.

    Eur. J. Vasc. Endovasc. Surg.

    (1998)
  • P. Ortenwall et al.

    Reduced platelet deposition on seeded versus unseeded segments of expanded polytetrafluoroethylene grafts: clinical observations after a 6-month follow-up

    J. Vasc. Surg.

    (1989)
  • P. Ortenwall et al.

    Endothelial cell seeding reduces thrombogenicity of Dacron grafts in humans

    J. Vasc. Surg.

    (1990)
  • M. Herring et al.

    Endothelial seeding of polytetrafluoroethylene femoral popliteal bypasses: the failure of low-density seeding to improve patency

    J. Vasc. Surg.

    (1994)
  • K.A. Kesler et al.

    Enhanced strength of endothelial cell attachment on polyester elastomer and polytetrafluoroethylene graft surfaces with fibronectin substrate

    J. Vasc. Surg.

    (1986)
  • J.E. Rosenman et al.

    Kinetics of endothelial cell seeding

    J. Vasc. Surg.

    (1985)
  • S.K. Williams et al.

    Human microvessel endothelial cell isolation and vascular graft sodding in the operating room

    Ann. Vasc. Surg.

    (1989)
  • M. Vici et al.

    Electron microscopic and immunocytochemical profiles of human subcutaneous fat tissue microvascular endothelial cells

    Ann. Vasc. Surg.

    (1993)
  • J.T. Sugimoto et al.

    Pericardial cells for graft seeding: isolation, culture and identification

    Ann. Vasc. Surg.

    (1989)
  • M. Deutsch et al.

    Clinical autologous in vitro endothelialization of infrainguinal ePTFE grafts in 100 patients: a 9-year experience

    Surgery

    (1999)
  • J.M. Bellon et al.

    Mesothelial versus endothelial cell seeding: evaluation of cell adherence to a fibroblastic matrix using 111In oxine

    Eur. J. Vasc. Endovasc. Surg.

    (1997)
  • M. Herring et al.

    Endothelial seeding of polytetrafluoroethylene popliteal bypasses

    J. Vasc. Surg.

    (1987)
  • M. Kadletz et al.

    Implantation of in vitro endothelialized polytetrafluoroethylene grafts in human beings. A preliminary report

    J. Thorac. Cardiovasc. Surg.

    (1992)
  • H. Magometschnigg et al.

    Prospective clinical study with in vitro endothelial cell lining of expanded polytetrafluoroethylene grafts in crural repeat reconstruction

    J. Vasc. Surg.

    (1992)
  • Q. Shi et al.

    Evidence for circulating bone marrow-derived endothelial cells

    Blood

    (1998)
  • S. Gojo et al.

    In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells

    Exp. Cell Res.

    (2003)
  • M. Reyes et al.

    Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells

    Blood

    (2001)
  • A.P. Beltrami et al.

    Adult cardiac stem cells are multipotent and support myocardial regeneration

    Cell

    (2003)
  • M. Boyer et al.

    Isolation of endothelial cells and their progenitor cells from human peripheral blood

    J. Vasc. Surg.

    (2000)
  • C.A. Ambler et al.

    Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway

    Dev. Biol.

    (2003)
  • C. Kalka et al.

    VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease

    Ann. Thorac. Surg.

    (2000)
  • V. Bhattacharya et al.

    Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34(+) bone marrow cells

    Blood

    (2000)
  • A. Kawamoto et al.

    Transplantation of endothelial progenitor cells for therapeutic neovascularization

    Cardiovasc. Radiat. Med.

    (2002)
  • T. Miyata et al.

    Delayed exposure to pulsatile shear stress improves retention of human saphenous vein endothelial cells on seeded ePTFE grafts

    J. Surg. Res.

    (1991)
  • Cited by (0)

    View full text