AbstractOrganic/hydroxyapatite (HA) hybrid composites are promising materials for orthopedic applications. Proteinoid/HA hybrid microsphere composite is an ideal material for bioresorbable and biocompatible three‐dimensional scaffolds. Proteinoids are thermally condensed mixtures of amino acids, forming microspheres via self‐assembly of proteinoid chains. Synthesis of an onion‐type multilayer proteinoid/HA hybrid composite is achieved by thermally condensing a mixture of amino acids in the presence of commercially available HA. Proteinoid/HA microsphere composite of about 40 μm are achieved as a result of heterogeneous nucleation of HA on proteinoids chains. The formation mechanism is based on the interaction between calcium ions of HA and carboxyl side groups of proteinoid. The morphology was gleaned by scanning electron microscopy, and the organic and inorganic constituents were characterized by several analytical methods. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.