In this work, a series of biodegradable and pH-responsive hydrogels based on polyphosphoester and poly (acrylic acid) are presented. A novel biodegradable macro-crosslinker alpha-methacryloyloxyethyl omega-acryloyl poly(ethyl ethylene phosphate) (HEMA-PEOP-Ac) was synthesized by first ring-opening polymerization of the cyclic monomer 2-ethoxy-2-oxo-1,3,2-dioxaphospholane using HEMA as the initiator and Sn(Oct)(2) as catalyst, and subsequent conversion of hydroxyl into vinyl group. The hydrogels were then fabricated by the copolymerization of the macromonomer with acrylic acid, and their swelling/deswelling and degradation behaviors were investigated. The results demonstrated that the crosslinking density and pH values of media strongly influenced both the swelling ratio and the degradation rate of the hydrogels. The rheological properties of these hydrogels were also studied from which the storage modulus (G') showed clear dependence on the crosslinking density. MTT and "live/dead" assay showed that these hydrogels were compatible to fibroblast cells, not exhibiting apparent cytotoxicity even at high concentrations. Moreover, in vitro bovine serum albumin release from these hydrogels was also investigated, and it could be found that the release profiles showed a burst effect followed by a continuous release phase, and the release rate was inversely proportional to the crosslinking density of hydrogels. (C) 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1919 1930, 2010