Abstract: A composition is provided, which is capable of generating hard tissue when introduced in a mammalian subject and comprises a) an ionic complex of i) chitosan and ii) a negatively charged polysaccharide selected from the group consisting of heparin, heparan sulfate and dextran sulfate, and b) a hard tissue generating growth factor, said ionic complex being a carrier for said hard tissue generating growth factor. Also provided are a method of preparation in vitro of a bone graft substitute using the composition, a kit for carrying out the method, as well as use of the composition in the preparation of a medical device for generation of hard tissue in a mammalian subject in need thereof, and a method of generation of hard tissue at a desired site in a mammalian subject in need thereof.