The objective of this study was to investigate the surface modification of a natural bone substitute, Bio-Oss, coated with a synthetic polymer poly-D,L-lactide (PLA), in order to improve cell growth. Bio-Oss is a natural bone substitute made of the mineralized portion of bovine bone. The material is used mainly to fill bone defects in periodontal and maxillofacial surgery and permit reossification. Poly-a-hydroxyacids such as polylactic acid are receiving an increasing attention due to their ability to retain a great quantity of water, good biocompatibility, low interfacial tension, and minimal mechanical and frictional irritation. All of these features are appealing from the perspective of bioenvironmental mimicking. The human osteosarcoma cell line SAOS-2 was added to the top of scaffolds uncoated or coated with PLA and incubated at 37 degrees in 5% CO(2) for 15 days. PLA-coated scaffolds improved cell growth. Polymer degradation behaviour, extraction and measurement of the extracellular matrix proteins of the cultured scaffolds (such as decorin, fibronectin osteocalcin, osteonectin, osteopontin and type-I and type-III collagen), immunolocalization of bone proteins and morphological analysis of the scaffolds confirmed the bioactive properties of Bio-Oss/PLA4M suggesting that it could be a valuable grafting material.