Biomedical Engineering Reference
In-Depth Information
human embryonic stem cell-derived cardiomyocytes (hESC-CMs), human
embryonic stem cell-derived endothelial cells (hESC-ECs) or human
umbilical vein endothelial cells (HUVECs), and embryonic fi broblasts
(EmFs). They demonstrated that the pre-formed capillary-like network of
endothelial cells was able to connect to the normal blood supply of the host
upon implantation. 43
10.4 Injectable materials
The use of injectable biomaterials for cellular cardiomyoplasty is an emerg-
ing and promising fi eld in cardiac tissue engineering. The injectable scaf-
folds for cell delivery offer many advantages over the classic cardiac tissue
engineering approach using a solid scaffold. A well-designed injectable
biomaterial can maintain cell survival and promote cell development
towards integration with the healthy cardiac tissue, but at the same time
should not impose a mechanical load on the injured cardiac muscle. Injec-
tion of a liquid biomaterial which can then be solidifi ed in situ enables the
biomaterial to take the appropriate shape of the scar tissue, rather than
imposing on the heart muscle with a cardiac patch having a fi xed geometry.
Moreover, injecting the biomaterial into the scar tissue allows for an inti-
mate contact between the injected cells and the host tissue, as opposed to
a solid graft transplanted on the surface of the myocardium. More impor-
tantly, an injectable therapy can be administered by a less invasive
arthroscopic procedure or catheterization, which has a tremendous clinical
advantage over open-chest surgeries. Treating patients after an MI using a
simple injection into the damaged tissue with guided catheterization is
much less invasive than a cardiac patch implantation performed in an open
heart surgery.
Christman et al. were the fi rst to report on a fi brin glue biomaterial as an
injectable scaffold to deliver myoblasts to the ischemic myocardium. 19
Fibrin is typically cross-linked into a hydrogel by mixing fi brinogen, throm-
bin and factor XIII. The cross-linking reaction is initiated with the addition
of thrombin to the fi brinogen solution. The reaction kinetics requires a few
seconds depending on the thrombin concentration, and this in turn allows
the injection of the liquid solution which then solidifi es in situ . They
reported that the injection of cells with the fi brin glue did not enhance cell
retention after 24 h; however, cell survival after fi ve weeks was signifi -
cantly higher. The fi brin glue was maintained in the myocardium for up to
ten days before fully degrading - providing for a temporary biodegradable
scaffold which allows cell attachment through fi brin's Arg-Gly-Asp (RGD)
integrin binding sites. The fi brin glue injection also increased neovascular-
ization in the ischemic tissue. The myoblasts were typically observed sur-
rounded by arterioles in the scar tissue, which may also explain the high
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