To achieve the injectable hydrogel system in order to improve bone regeneration by locally delivering a protein drug including bone morphogenetic proteins, thermo-responsive injectable hydrogels composed of N-iso-propylacrylamide (NIPAAm) and vinyl phosphonic acid (VPAc) were prepared. The P(NIPAAm-co-VPAc) hydrogels were also biomineralized by urea-mediation method to create functional polymer hydrogels that deliver the protein drug and mimic the bone extracellular matrix. The loosely cross-linked P(NIPAAm-co-VPAc) hydrogels were pliable and fluid-like at room temperature and Could be injected through a small-diameter aperture. The lower critical solution temperature (LCST) of P(NIPAAm-co-VPAc) hydrogel was influenced by the monomer ratio of NIPAAm/VPAc and the hydrogel with a 96/4 molar ratio of NIPAAm/VPAc exhibited an LCST of similar to 34.5 degrees C. Water content was influenced by temperature, NIPAAm/VPAc monomer ratio, and biomineralization; however, all hydrogels maintained more than about 77% of the water content even at 37 degrees C. In a cytotoxicity study, the P(NIPAAm-co-VPAc) and biomineralized P(NIPAAm-co-VPAc) hydrogels did not significantly affect cell viability. The loading content of bovine serum albumin in hydrogel, which was used as a model drug, gradually increased with the amount of VPAc in the hydrogel owing to the ionic interaction between VPAc groups and BSA molecules. In addition, the release behavior of BSA from the P(NIPAAm-co-VPAc) hydrogels was mainly influenced by the drug loading content, water content, and biomineralization of the hydrogels. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 3460-3469, 2009