Temperature-sensitive poly (caprolactone-co-trimethylene carbonate)-poly(ethylene glycol)-poly(caprolactone-co-trimethylene carbonate) as in situ gel-forming biomaterial

We are reporting a new thermogelling poly(caprolactone-co-trimethylene carbonate)-poly(ethylene glycol) -poly(caprolactone-co-trimethylene carbonate) (PCTC-PEG-PCTC) triblock copolymer. By incorporating the comonomer (trimethylene carbonate) up to 25-40 wt % in the polycaprolactone block, the resulting PCTC-PEG-PCTC triblock copolymer achieved so] stability while keeping the thermogelling property in a physiologically important temperature range of 10-50 degrees C. The precipitation of the polymer in water at 20 degrees C was a concern for a poly(caprolactone)-poly(ethylene glycol) -poly(caprolactone) (PCL-PEG-PCL) system for practical applications (Macromolecules 2006, 39, 4873). The PCTC-PEG-PCTC triblock copolymer thermogel did not show the characteristic peaks of the polycaprolactone crystalline domain at 2 theta = 21.5 degrees and 23.5 degrees in the X-ray diffraction spectra. The sol-to-gel transition temperature of PCTC-PEG-PCTC aqueous solution could be controlled in a range of 15-30 degrees C by varying the composition and molecular weight of PCTC. The PCTC-PEG-PCTC was not degraded in a phosphate buffer saline for 50 days, whereas significant changes in molecular weight and composition of the polymer were observed for the polymer implanted in the subcutaneous layer of rats over the same period of time. The in situ formed hydrogel of PCTC-PEG-PCTC was investigated as a three-dimensional cell culture medium. Compared with the traditional culture on a plate (two-dimensional culture), the chondrocytes cultured in the in situ formed PCTC-PEG-PCTC hydrogel (three-dimensional culture) showed a higher expression of collagen type 11 and aggrecan and suppression of collagen type I (fibroblastic gene), suggesting the excellent differentiation of the cell in the PCTC-PEG-PCTC hydrogel.