Bacterial cellulose (BC) and hydroxyapatite (HA) possess unique structures and excellent biocompatibility. Considerable work has been performed to develop composites that promote bone repair. However, the use of BC/HA composites is limited because the lack of corresponding enzymes makes them non-degradable in vivo. In the present study, C6-carboxylated bacterial cellulose (TBC) was prepared in a bromide-free system. Several composite methods of TBC and HA are compared, including in situ formation, physical mixing and biomineralization. Composite sponges prepared by different methods were characterized by tensile testing, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and in vivo degradation. The structural anisotropy of various sponges was analyzed to quantitatively evaluate their microstructure. The results suggest that the interaction between HA and TBC nanofibers has a large influence on microstructure and macroscopic properties. Moreover, the structural anisotropy and the speed of granulation ingrowth were strongly interdependent. This improved understanding of slowly degrading BC-based materials suggests that modified cellulose-based materials can be made degradable by altering their microstructure.