Synthesis and in vivo evaluation of a novel hydroxyapatite/collagen–alginate as a bone filler and a drug delivery carrier of bone morphogenetic protein

Recently, hydroxyapatite/collagen (HAp/Col) nanocomposites incorporated into bone remodeling processes have been developed. Because bone tissue reaction to the composites is obviously suitable for bone tissue engineering, a novel HAp/Col–alginate hybrid material, as one variety of the HAp/Col implants, was prepared to expand the limited applications of the composite. The ability of HAp/Col–alginate as a bone filler was investigated in the rat femur and as a carrier of BMP using an ectopic bone formation model. Active bone formation around the material and tissue invasion into the material were observed throughout the experiment in bone, compared to those observed for simple alginate and porous HA. Furthermore, HAp/Col–alginate was investigated as a carrier of recombinant human bone morphogenetic protein 2 (rh-BMP2). The HAp/Col–alginate (20 μl) with the rh-BMP2 (100 μg/ml, 15 μl) showed bone formation throughout the implant 5 weeks after implantation without obvious deformation of the material, whereas bone formation was observed only in a part of a squashed collagen sponge.