Biomaterials in cardiac restoration therapy - Biomaterials and Devices for the Circulatory System - page 272

survival of the injected myoblasts when delivered with the fi brin glue.
Although the injection of fi brin increased micro-vessel formation, this dif-
ference was not statistically signifi cant when compared to injection with
bovine serum albumin (BSA). Fibrin is generally known to induce angio-
genesis in vivo ; 20 however, injection of many other materials into the myo-
cardium is also known to induce angiogenesis, and this may explain why
the fi brin did not result in a signifi cantly higher angiogenic response. In
addition to increasing cell survival, fi brin also prevents cardiac remodeling
after MI. 18,19
Kofi dis et al. injected Matrigel combined with mouse embryonic stem
cells 44,45 into an infarcted myocardium of the adult rat. The Matrigel solidi-
fi ed at 37 °C after a few hours in situ . They reported an improvement in
cardiac function both with and without cells. Hence, the real contribution
of the stem cells embedded in the Matrigel was not clear from this investi-
gation. Another injectable system for cell delivery is the self-assembling
peptide nanofi ber matrix which was presented by Davis et al. 26 In this study,
neonatal cardiomyocytes were injected together with the self-assembling
peptide to healthy mice hearts. Only a very small portion of the injected
cells survived in the matrix after seven days. The authors note that the
injection of the matrix with the cells increased the recruitment of native
progenitor myocytes into the polypeptide matrix. The low survival rate of
the injected cardiomyocytes in this system underscores the importance of
properly designing an injectable cell delivery biomaterial for the special
requirements of cardiomyocytes.
A new type of biosynthetic material based on fi brinogen was recently
developed by our group for the intended purpose of cardiac cell therapy.
The injectable polymer has bioactivity similar to native fi brin, with the
added advantage of controllable physical properties and biodegrada-
tion. 46-48 The biomaterial is made by conjugating PEG with denatured
fi brinogen in solution to form a PEGylated fi brinogen liquid precursor.
The liquid precursor is assembled into a three-dimensional hydrogel scaf-
fold using non-toxic photo-polymerization. 49 The fi brinogen molecule
contains functional biological sequences which are essential for cell
invasion and tissue remodeling. These include proteolytic cleavage sites
sensitive to matrix metalloproteinases (MMPs) and plasmin, two common
proteases in cardiac remodeling, as well as adhesion sites such as RGD. 50
The PEG constituent of the PEGylated fi brinogen hydrogel is widely
used in biomedical and pharmacological applications because of its inert
characteristics and low immunogenicity. 51,52 Using the unique properties
of the PEG-conjugated fi brinogen allows one to control the hydrogel
degradation rate, reduce the immune response to the graft and control
the mechanical properties of the hydrogel by altering the composition of
the matrix. 48

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