(64a) Improving Cardiac Function after Myocardial Infarction Via Local Delivery of Mydgf Using an Injectable Polyester-Based Hydrogel

Local Delivery of Mydgf Using an Injectable Polyester-Based
Hydrogel to Treat Myocardial Infarction

Yung-Hao Tsou, Xiaoyang Xu

Department of Chemical and Materials
Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA

Email: xiaoyang@njit.edu

Abstract:

Under
cardiac dysfunction, myocardial infarction (MI)
can cause morbidity and mortality. Intramyocardial bomaterial injection therapy
is considered an advantageous means by which cardiac performance can be
enhanced after experiencing ischemic myocardial infarction. In order to decrease cardiac functional loss, a wide variety of
hydrogels that delivery cells or bioactive molecule directly to the heart after
MI are currently being investigated. Hydrogels hold
great promise for a wide range of biomedical applications. Among them,
injectable hydrogels have newly emerged as powerful 3D materials for tissue
engineering and drug delivery by offering minimally invasive, localized,
cavity-filling and biodegradable scaffolding features. Here, we introduce
a new material and develop an in vivo application of a polyester based hydrogel
in the treatment of MI. Myeloid-derived growth factor (Mydgf), a new protein secreted by bone
marrow-derived monocytes and macrophages, could responsible for cardiac
myocyte survival and angiogenesis, and promotes cardiac recovery after MI.
In this study, the effect of Mydgf as a hydrogel has
been assessed in a rat MI model. Injecting this polyester-based hydrogel into
the MI area provides a means to reduce scar formation and infarct size,
increase wall thickness and neovascularization, which may promote a significant
functional improvement. Additionally, Mydgf
shows angiogenic activity by motivating the migration and tubular formation of
human umbilical vessel endothelial cells (HUVECs). It can also prevent
cardiomyocytes from apoptosis. In general, this novel polyester based hydrogel
can be injected into a beating heart and can remain localized for a clinically
effective period. The hydrogel loaded
with Mydgf induced significant cardiac
functional and morphological recovery, attenuated apoptosis, and increased
microvessel density in the infarcted hearts. This conception of combination
approach will become a robust therapeutic strategy for the treatment of MI.

Method and
Results:

Polyester
oligomers with tunable mechanical properties have been successfully synthesized
from biocompatible monomers including citric acid, poly (ethylene glycol)
(PEG)-diol and thiol based moieties via a facile polycondensation reaction. The
polyester-based hydrogels loaded with Mydgf (Figure 1A) were injected into the
infarction site of rats. In Figure 1B, the H&E and Masson’s trichrome
staining shows promising results of Mydgf loaded hydrogels compared with
control group (rats with MI only).

Figure 1: (A) Polyester based hydrogels containing
Mydgf protein; (B) The morphologies of the left
ventricle by H&E staining and Masson's trichrome staining.

Conclusion

In
this study, we confirmed the suitability of using polyester-based hydrogel for the local, controlled,
intramyocardial delivery of Mydgf. Injection of the
Mydgf-hydrogel into the LV of rats with AMI showed significant improvements in
cardiac morphology and functionality at 4 weeks relative to the controls. We
further reveal that the functional roles
of Mydgf-hydrogel in promoting angiogenesis and reducing cardiac cell
apoptosis.