Some gel types have been reported to prevent left ventricular (LV) remodeling in myocardial infarction (MI) animal models. In this study, we tested biodegradable thermoresponsive gels. Poly(L-lactic acid)-poly(ethylene glycol) (PLLA-PEG) and poly(D-lactic acid)-poly(ethylene glycol) (PDLA-PEG) were synthesized by the polycondensation of l- and D-lactic acids in the presence of PEG and succinic acid. Each of these block copolymers was used to prepare particles dispersed in an aqueous medium and mixed together to obtain a PLLA-PEG/PDLA-PEG suspension, which was found to show a sol-to-gel transition around the body temperature by the stereocomplex formation of enantiomeric PLLA and PDLA sequences. In the present study, the G' of the PLLA-PEG/PDLA-PEG suspension in the rheological measurement remained as low as 1 Pa at 20 °C and increased 2 kPa at 37 °C. The sol-gel systems of PLLA-PEG/PDLA-PEG might be applicable to gel therapy. The effect of the PLLA-PEG/PDLA-PEG gel injection was compared with that of a calcium-crosslinked alginate gel and saline in a rat MI model. The percent fractional shortening improved in the PLLA-PEG/PDLA-PEG (20.8 ± 4.1%) and alginate gel (21.1 ± 4.8%) compared with the saline (14.2 ± 2.8%) with regard to the echocardiograph 4 weeks after the injection (p < 0.05). There were reduced infarct sizes in both PLLA-PEG/PDLA-PEG gel and alginate gel compared with the saline injection (p < 0.05). Moreover, a greater reduction in LV cavity area was observed with the PLLA-PEG/PDLA-PEG gel than with the alginate gel (p = 0.06). These results suggest that the PLLA-PEG/PDLA-PEG gel should have high therapeutic potential in gel therapy for LV remodeling after MI.
Keywords: Myocardial infarction; Poly(L-lactic acid); Stereocomplex formation; Thermoresponsive gel.