The objective of this study was to elucidate the role of hydroxyvalerate (HV) composition in polyhydroxy butyrate valerate (PHBV) copolymer film on the degradation of copolymer and osteoblastic cell activity. Degradation was studied by monitoring time-dependent changes in mass and chemical composition of the macroporous films. The mass loss of PHBV film upon 19 weeks of exposure to pH 7.4 phosphate buffer medium was found to range from 2.8% to 9.2% with a strong dependence on the original composition of the copolyester film and morphology. Tapping mode atomic force microscopy (TMAFM) was used to examine the roughness change of polyester films due to exposure to buffer medium. Chemical analysis of the degraded film was carried out using NMR to aid in the interpretation of the mass loss and TMAFM data. The NMR results showed a significant decrease in the mol %. of HV content in the degraded PHBV film. Additionally, we established that UMR-106 cell proliferation on macroporous PHBV matrix is minimally enhanced by the HV content of PHBV copolymer. Information provided by this study can be used in the selection of appropriate PHBV copolymer for clinical use where the biopolymer needs to remain physically intact and chemically unchanged during the intended period of biomedical application. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 116: 3225-3231, 2010