The synthesis and purification of poly(lactide ethylene oxide fumarate) (PLEOF) involved using organic solvents and triethylamine, an acid scavenger that produces toxic complexes. These issues were addressed by using potassium carbonate as an alternative acid scavenger and CO2 gas expanded solution as a media for reaction. Conducting the reaction at these conditions resulted in reducing the number of stages for purification, enhancing the yield of polymerization by 31%, and increasing the fumarate fraction by 110% compared with conventionally produced polymers. Therefore, the capacity of polymer for crosslinking was significantly promoted that resulted in elevating the compression modulus of hydrogel by 119%. Eliminating the toxic chemical residues and strengthening the mechanical property of PLEOF led to enhancement in primary osteoblast cell proliferation on this hydrogel. The new strategy for the synthesis of PLEOF had paramount impact on the characteristics of this polymer and enhanced its biocompatibility for tissue engineering applications, particularly bone repair. (c) 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1291-1299