Injection of a bulking material into the ventricular wall has been proposed as a
therapy to prevent progressive adverse remodeling due to high wall stresses that develop after
myocardial infarction. Our objective was to design, synthesize and characterize a biodegradable, thermoresponsive
hydrogel for this application based on copolymerization of
N-isopropylacrylamide (NIPAAm),
acrylic acid (AAc) and
hydroxyethyl methacrylate-
poly(trimethylene carbonate) (
HEMAPTMC). By evaluating a range of monomer ratios, poly(NIPAAm-co-AAc-co-
HEMAPTMC) at a feed ratio of 86/4/10 was shown to be ideal since it formed a
hydrogel at 37 degrees C, and gradually became soluble over a 5 month period in vitro through hydrolytic cleavage of the PTMC residues.
HEMAPTMC, copolymer and degradation product chemical structures were verified by NMR. No degradation product cytotoxicity was observed in vitro. In a rat chronic
infarction model, the infarcted left ventricular (LV) wall was injected with the
hydrogel or
phosphate buffered saline (PBS). In the PBS group, LV cavity area increased and contractility decreased at 8 wk (p<0.05 versus pre-injection), while in the
hydrogel group both parameters were preserved during this period. Tissue ingrowth was observed in the
hydrogel injected area and a thicker LV wall and higher capillary density were found for the
hydrogel versus PBS group. Smooth muscle cells with contractile phenotype were also identified in the
hydrogel injected LV wall. The designed poly(NIPAAm-co-AAc-co-
HEMAPTMC)
hydrogel of this report may thus offer an attractive
biomaterial-centered treatment option for ischemic
cardiomyopathy.