Heart valve and arterial tissue engineering

Abstract

In the industrialized world, cardiovascular disease alone is responsible for almost half of all deaths. Many of the conditions can be treated successfully with surgery, often using transplantation techniques; however, autologous vessels or human-donated organs are in short supply. Tissue engineering aims to create specific, matching grafts by growing cells on appropriate matrices, but there are many steps between the research laboratory and the operating theatre. Neo-tissues must be effective, durable, non-thrombogenic and non-immunogenic. Scaffolds should be bio-compatible, porous (to allow cell/cell communication) and amenable to surgery. In the early days of cardiovascular tissue engineering, autologous or allogenic cells were grown on inert matrices, but patency and thrombogenicity of grafts were disappointing. The current ethos is toward appropriate cell types grown in (most often) a polymeric matrix that degrades at a rate compatible with the cells' production of their own extracellular matrical proteins, thus gradually replacing the graft with a living counterpart. The geometry is crucial. Computer models have been made of valves, and these are used as three-dimensional patterns for mass-production of implant scaffolds. Vessel walls have integral connective tissue architecture, and application of physiological level mechanical forces conditions bio-engineered components to align in precise orientation. This article reviews the concepts involved and successes achieved to date.

Figure 1

Transmission electron micrograph of porcine aortic wall myofibroblasts at the surface (arrow) of a collagen sponge matrix. The cells are spindle‐shaped with their long axes parallel to the surface of the construct. M is a mitotic figure. Bar = 4 µm.

Figure 2

Transmission electron micrograph of extracellular matrix fibres produced by cells at the centre of a collagen matrix (collagen, solid arrow; elastin fine arrow). Bar = 0.6 µm.

Figure 3

Plan of the structure of the culture force monitor indicating relationships of the culture well, force transducer and computer.

Figure 4

Plan of the structure of the tensioning‐culture force monitor showing the addition of a microstepping motor.

Figure 5

Plan of the structure of the multicue bioreactor. The tissue construct cassette holds the tubular neo‐vascular specimen and the pulsatile pump delivers culture medium at physiological forces comparable with those produced by the heart.

Figure 6

En face preparation of porcine aortic wall cells on a small intestine submucosa matrix in static culture for 7 days (a) and bioreacted in the M‐CB for 7 days under pulmonary artery conditions (b). Direction of culture media flow, large closed arrow; direction of circumferential strain due to applied pressure, open arrows; cell nuclei, small arrows. (Light micrograph, haematoxylin and eosin stained, original magnification × 40.)