An in situ gel-forming heparin-conjugated PLGA-PEG-PLGA copolymer

Novel heparin-conjugated PLGA-PEG-PLGA hydrogels were prepared via Michael-type addition between thiolated heparin and PLGA-PEG-PLGA diacrylate. The thiolated heparin (HP-SH) was conjugated with thiolacid dihydrazide followed by reduction. The structure and the thiol determination of obtained HP-SH were characterized by H-1 NMR and the Ellman method. Anticoagulant activity and pK(a) of the HP-SH were determined by aPTT test and UV absorbance measurement which were 79.3% and 10.5, respectively. The PLGA-PEG-PLGA diacrylate was synthesized by bulk ring-opening polymerization of D, L-lactide (DLLA) and glycolide (GA) with PEG and stannous 2-ethylhexanoate, followed by the acrylation of the terminal groups. HP-SH was then conjugated to PLGA-PEG-PLGA diacrylate by Michael addition. Phase diagrams of the hydrogels were obtained by vial tilting; the release of heparin from the hydrogels exhibited temperature dependent sol-gel transition behavior. These in situ-forming heparin-conjugated hydrogels are novel as injectable and tissue-compatible scaffold formation, thermo-sensitivity, and growth factor binding.