Biomedical Engineering Reference
In-Depth Information
One of the first attempts to provide a supportive scaffold for MI dates from
1937, when Dr. O'Shaughnessy used omental wrapping to promote neovascular-
ization [
237
] of the ischemic organ. Since then, the field has experienced an
incredible boost, especially during the last decade. In the following sections, we
will describe some of the approaches developed and discuss their strengths and
pitfalls.
5.4.1 Injectable Materials and Cell Microencapsulation
Initial studies focused on the use of injectable materials that could improve cell
retention and provide structural anchorage [
238
] while allowing the use of less
invasive ways of delivery like catheter-based injections.
Early experiments were performed by combining the cells with biomaterials
derived from the extracellular matrix, like collagen, fibrin or gelatin. Also, ma-
trigel or other factors that provided a favorable environment rich in cytokines and
growth factors were tested. In general, an increased survival rate of the trans-
planted cells was shown and consequently, a greater improvement of the cardiac
function of the treated hearts [
239
,
240
].
Thanks to this relatively simple approach, the trophic effect exerted by the cells
was boosted by increasing their survival and engraftment in the tissue. Moreover,
importantly, it has been observed that some of the injected materials can exert a
positive effect themselves, as has been shown, for example, for alginate. This
material is liquid, but suffers a phase transition to hydrogel when injected into the
desired tissue, as the local calcium concentration increases. Thus, the groups of
Dr. Cohen and Dr. Leor have shown that when recent (7 days) or old (60 days) rat
infarcts were treated with this alginate solution, wall thickness was significantly
increased, while both systolic and diastolic dilatation and dysfunction were pre-
vented. Interestingly, the effect was even superior to that of neonatal CM trans-
plantation [
241
]. Moreover, this benefit was also confirmed in a pre-clinical model of
myocardial infarction in swine, showing a positive left ventricular remodeling [
242
].
Furthermore, alginate also provides means for material modification, as demon-
strated by the same group. The former approach was altered by linking IGF1 and
HGF to the hydrogel, supplying these cytokines with proteolysis protection. When
injected in a rat model of acute MI, modified alginate sequentially released the
molecules, which preserved ventricle thickness, attenuated infarct expansion and
fibrosis deposition, and also increased angiogenesis and induced CM-cycle re-entry
[
243
]. In a different approach, the group led by Randall Lee conjugated the adhesion-
promoting motif arginine-glycine-asparagine (RGD) sequence to alginate and
showed its therapeutic capacity to treat a model of chronic MI in rat [
244
].
Self-assembling peptide nanofibers [
245
] have also proved their therapeutic
potential for angiogenesis, growth factor-release and cell-delivery [
246
-
248
]. Lin
et al. [
249
] compared the combination of nanofibers with BM-MNC in a pig
preclinical model of MI with nanofiber or cell injection alone. It was found that, in
