Tissue Eng Regen Med.  2017 Oct;14(5):507-516. 10.1007/s13770-017-0067-9.

Effect of Thermoresponsive Poly(L-lactic acid)-poly (ethylene glycol) Gel Injection on Left Ventricular Remodeling in a Rat Myocardial Infarction Model

• Somekawa S
• Mahara A
• Masutani K
• Kimura Y
• Urakawa H
• Yamaoka T

• KMID: 2394985
• DOI: http://doi.org/10.1007/s13770-017-0067-9

Abstract

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 Land 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 ℃ and increased 2 kPa at 37 ℃. 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 calciumcrosslinked 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.

Keyword

Myocardial infarction; Poly(L-lactic acid); Thermoresponsive gel; Stereocomplex formation

MeSH Terms

Animals
Body Temperature
Gels
Lactic Acid
Models, Animal
Myocardial Infarction*
Rats*
Succinic Acid
Ventricular Remodeling*
Gels
Lactic Acid
Succinic Acid