Biomaterials developed for controlled drug delivery have demonstrated excellent results in the present study. A biomaterial prepared using hydroxyapatite (HAp) was shown to have a hollow structure with the presence of interconnected pores to house drug carriers. The poly(lactic-co-glycolic acid) particles were used as drug carriers loaded with dexamethasone, a corticosteroid that is known to promote osteoinduction. The surface of the drug carriers was modified using polyethyleneimine, and then conjugated to the surface of HAp granules. The hollow HAp granules had drug carriers on both their inner and outer surfaces and showed a controlled drug release rate that was comparable to that of granules containing drug carriers on their outer surface alone. The pores were designed for insertion of drug carriers and preosteoblasts. Consequently, the biomaterials influenced cellular behavior by first promoting cell proliferation and then inducing early stage osteogenic differentiation. The effects of controlled release rate were evidenced for up to two weeks after cell seeding, resulting in an increase of osteogenic differentiation. In summary, drug carriers loaded onto hollow HAp granules were shown to be suitable for patients who require replacement of missing bone for repair of bone fractures that are extremely complex, pose a significant health risk to the patient, or fail to heal properly. Biotechnol. Bioeng. 2015;112: 1936-1947. (c) 2015 Wiley Periodicals, Inc.