Biomaterials in cardiac restoration therapy - Biomaterials and Devices for the Circulatory System - page 273

We have shown in 3-D in vitro experiments that the hydrogel stiffness
affects cardiomyocyte contractility. 53 Based on these fi ndings, we were able
to design a hydrogel matrix with the optimal compliance to enable the
formation of a synchronously contracting tissue analogue when seeded with
neonatal cardiomyocytes. We also demonstrated a similar effi cacy with the
PEGylated fi brinogen matrix using h-ESC-CM as a more relevant cell
source for future clinical applications. 54 In vivo , the PEGylated fi brinogen
hydrogel was injected to infracted adult rat hearts as a cell carrier with the
neonatal rat cardiomyocytes or the h-ESC-CM (unpublished data). The
injected cells survived in the infarcted tissue after 30 days and improved
cardiac functionality as evaluated by means of echocardiography. Injection
of the hydrogel in combination with neonatal cardiomyocytes produced the
best results. A modest improvement was seen when injecting cell or bio-
polymer alone; however, this change was very small in comparison with the
combined treatment of cells with biopolymer. The injection of neonatal
cardiac cells alone or the hydrogel alone caused a slight increase in frac-
tional shortening (FS) change (3.1 5.3%, respectively).

The combined injection resulted in a 26% improvement in FS change.
Other measured parameters (left ventricular diastolic diameter, anterior
wall thickness, and wall motion score) gave similar results in favor of the
combined injection.
The mechanical properties of the PEGylated fi brinogen also physically
stabilized the cardiac geometry without limiting the cell spreading required
to enable cell-cell contacts (indicated by Cx43 labeling). Moreover, the
grafted cells were seen aligned with the host cells in vivo . We also demon-
strated that changing the ratio of PEG to fi brinogen causes the degradation
rate of the hydrogel matrix to slow down signifi cantly both in vitro and
in vivo (unpublished data). Future experiments will include a more precise
optimization of the hydrogel properties to be able to maximize the advan-
tages of this tunable biomaterial for cardiac cell therapy in clinical
applications.

± 6.6% and 0.5 ±

￿ ￿ ￿ ￿ ￿

10.5 Conclusions

The successful implementation of a cardiac cell therapy for treating myo-
cardial infarction will likely require an appropriate biomaterial cell carrier.
A number of investigations are currently underway to identify a biomate-
rial that can localize the effectiveness of the cardiac cell graft without
compromising cell survival and host integration. Biomaterials may also be
effective in augmenting the remodeling process following an MI, provid-
ing short-term improvements in cardiac function. For successful clinical
application of biomaterial-based cardiac restoration, it is essential to intro-
duce new materials that can accommodate the requirements of precisely