Since 1980, natural coral exoskeleton has been widely used as bone graft substitute. Despite numerous in vitro and in vivo studies, there is still a lack of knowledge concerning the organic matrix associated with coral exoskeleton (COM). In fact, some surgical interventions have failed and this has sometimes been attributed to the exoskeleton organic matrix. For others, only amino acids are present in the matrix after coral preparation for clinical use. The objective of this study was to extract the exoskeleton organic matrix to carry out biochemical analysis and study its specific cytocompatibility. Demineralized bone powder (DBP) was used as control. A decalcification process was used to extract CONI and DBP. Protein, carbohydrate and glycosaminoglycan analysis was carried out in DBP and CONI using classical staining methods. Human bone marrow cells were cultured in the presence of 20, 40, 80, 160 mug Of COM or DBP for 24, 48 and 72 h. The methods used to analyze COM and DBP effects were scanning electron microscopy, immunocytochemistry. manual cell count, and cyto-compatibility assay (Neutral red and MTT tests). Results showed that in spite of treating coral before clinical use, a COM was present in which GAG, protein and carbohydrate were found. The in vitro cytocompatibility of COM was confirmed for 20 and 40 mug values but was less pronounced for 80 and 160 mug levels. (C) 2001 Elsevier Science Ltd. All rights reserved.