KMID : 1377020170140050507
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Tissue Engineering and Regenerative Medicine 2017 Volume.14 No. 5 p.507 ~ p.516
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Effect of Thermoresponsive Poly(L-lactic acid)? poly(ethylene glycol) Gel Injection on Left Ventricular Remodeling in a Rat Myocardial Infarction Model
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Somekawa Shota
Mahara Atsushi Masutani Kazunari Kimura Yoshiharu Urakawa Hiroshi Yamaoka Tetsuji
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Abstract
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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 G0 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 calciumcrosslinked alginate gel and saline in a rat MI model. The percent fractional shortening improved in the PLLA?PEG/ PDLA?PEG (20.8 ¡¾ 4.1%) and alginate gel (21.1 ¡¾ 4.8%) compared with the saline (14.2 ¡¾ 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.
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KEYWORD
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Myocardial infarction, Poly(L-lactic acid), Thermoresponsive gel, Stereocomplex formation
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