November 2008
Published by the American Chemical Society
Volume 9, Number 11
Copyright 2008 by the American Chemical Society
Reviews Biofunctionalization of Biomaterials for Accelerated in Situ Endothelialization: A Review Achala de Mel,† Gavin Jell,‡,§ Molly M. Stevens,‡,§ and Alexander M. Seifalian*,†,⊥ Centre of Nanotechnology, Biomaterials and Tissue Engineering, UCL Division of Surgery & Interventional Science, University College London, London, United Kingdom, Department of Materials and Institute of Biomedical Engineering, Imperial College London, London, United Kingdom, and University Department of Surgery, Royal Free Hampstead NHS Trust Hospital, London, United Kingdom Received June 24, 2008; Revised Manuscript Received August 7, 2008
The higher patency rates of cardiovascular implants, including vascular bypass grafts, stents, and heart valves are related to their ability to inhibit thrombosis, intimal hyperplasia, and calcification. In native tissue, the endothelium plays a major role in inhibiting these processes. Various bioengineering research strategies thereby aspire to induce endothelialization of graft surfaces either prior to implantation or by accelerating in situ graft endothelialization. This article reviews potential bioresponsive molecular components that can be incorporated into (and/or released from) biomaterial surfaces to obtain accelerated in situ endothelialization of vascular grafts. These molecules could promote in situ endothelialization by the mobilization of endothelial progenitor cells (EPC) from the bone marrow, encouraging cell-specific adhesion (endothelial cells (EC) and/or EPC) to the graft and, once attached, by controlling the proliferation and differentiation of these cells. EC and EPC interactions with the extracellular matrix continue to be a principal source of inspiration for material biofunctionalization, and therefore, the latest developments in understanding these interactions will be discussed.
1. Introduction Coronary artery disease is a major cause of mortality and morbidity1 with two main surgical options available. Percutaneous transluminal coronary angioplasty/stenting is used in cases of less than 70% occlusion, and bypass surgery is performed in cases with a greater degree of occlusion. Drug eluting stents have within the last 10 years received considerable research attention and some notable successes in clinical trials.2-5 However, issues relating to the drug elution lifespan and the consequences once this elapses remain, including incidences of late thrombosis and restenosis.6 Furthermore, there is evidence to suggest that drug elution may inhibit endothelial cell (EC) proliferation.6 For patients requiring bypass surgery, saphenous vein, internal mammary artery, internal thoracic, or radial artery * To whom correspondence should be addressed. Tel.: 0044 20 7830 2901. E-mail:
[email protected]. † University College London. ‡ Department of Materials, Imperial College London. § Institute of Biomedical Engineering, Imperial College London. ⊥ Royal Free Hampstead NHS Trust Hospital.
are the grafts of choice, however, 5-30% of patients have no suitable veins/arteries available due to previous use or diseased vein wall. A thriving synthetic graft industry therefore exists, largely concerning expanded polytetrafluroethylene (ePTFE) or polyethylene terephalate (Dacron). However, despite their prevalence, these grafts offer low patency due to noncompliance, thrombogenic surface, and the tendency to form intimal hyperplasia (IH).7 Existing synthetic materials are also not suitable for coronary bypass or for small caliber (
