The aim of this work was to fabricate a macroporous scaffold from oyster shell by using an innovative combination of techniques. Crassostrea angulata shell characterized by a natural microporous structure (2-10 mu m) was used as raw material. Firstly, plate-like nanocrystals of AB-type carbonated hydroxyapatite (HA) were produced by hydrothermal conversion of fine-milled oyster shell powders. Secondly, interconnected macroporous scaffolds were prepared with the polymer replication method. The obtained scaffolds presented a biphasic structure of hydroxyapatite/beta-tricalcium phosphate (HA/beta-TCP) with a porosity of 91.4 +/- 1.2%, and showed an excellent permeability due to the open macropores (200-500 mu m) and interconnected micropores (100-500 nm) in macropore walls. The synthetic scaffolds were found to be non-cytotoxic and displayed better biocompatibility than pure HA scaffolds when seeded with pre-osteoblasts cells (MC3T3-E1). Therefore, the macroporous scaffolds derived from oyster shells would offer promising alternatives for bone tissue engineering applications. (C) 2011 Elsevier B.V. All rights reserved.