Biomaterials in cardiac restoration therapy - Biomaterials and Devices for the Circulatory System - page 264

dilation at the infarct site. After the initial infl ammatory phase, the synthesis
of MMP inhibitors is elevated, leading to an accumulation of collagen in
the infarct zone. This fi brogenic phase ends in the formation of a fi brotic
scar tissue in the infarct site as well as the formation of fi brous tissue in
locations that are remote to the infarct. 3
The objectives of cardiac restoration therapy are to augment the fi brotic
scar tissue in the infarct with functional cardiac muscle and to prevent the
unavoidable deterioration of the remaining healthy cardiac muscle. Several
approaches have been suggested to achieve these goals. The earliest attempts
at cardiac restoration therapy were focused on the direct injection of viable
cells into the infarcted myocardium. Different types of cells have been
employed for this purpose, including skeletal myoblasts, neonatal cardio-
myocytes, fi broblasts, smooth muscle cells, embryonic stem cells, and adult
stem cells (bone marrow progenitors). 4 Even though some studies showed
an improvement in cardiac function as a result of the cell injection/
infusion, 5,6 the percentage of surviving cells in the infarcted myocardium
was generally very low. 7,8 For example, Qian et al. showed that one hour
after intracoronary delivery of autologous bone marrow mononuclear cells,
only 7% of the cells appeared in the myocardium whereas more than 90%

of the cells were accumulated in the liver and the spleen. 8
The low cell survival following direct cell injection motivated the use of
biomaterials in cardiac restoration therapies. Two distinct categories of
biomaterial-based cardiac cell therapy were introduced: a tissue engineered
cardiac patch and an injectable biomaterial/cell graft. The tissue engineer-
ing method attempts to create a tissue analog in vitro which is to be
sutured directly onto the infarcted myocardium. The injectable biomaterial
approach is designed to deliver cell grafts locally. Generally, cardiac resto-
ration with injectable biomaterials is focused on of the use of liquid-to-solid
hydrogels as cell carriers that, when combined with cells, should increase
the cell survival and improve the overall contractility of the infarcted myo-
cardium. In spite of the enormous potential of cardiac cell therapy in this
regard, some recent studies have focused on using biomaterials alone to
stabilize the cardiac wall geometry and prevent cardiac remodeling, without
cell therapy. In this chapter we will cover the use of biomaterials for cardiac
restoration, including acellular biomaterial therapies, non-injectable bioma-
terials and injectable biomaterials.

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10.2 Acellular approaches

The use of an acellular approach in cardiac restoration is premised on
the hypothesis that a biomaterial can prevent the destructive cardiac remod-
eling process following MI by mechanically stabilizing the myocardial
wall following the acute infarction. In this context, both injectable and