Biphasic calcium phosphate microparticles for bone formation: benefits of combination with blood clot

Particulate forms of biphasic calcium phosphate (BCP) biomaterials below 500  μm are promising bone substitutes that provide with interconnected open porosity allowing free circulation of fluids and cells. Dispersion of the particles in the surrounding tissues at the time of implantation is a major drawback preventing from an easy use. We have asked whether blood clot could be a convenient natural hydrogel for handling BCP microparticles, and we hypothesized that blood clot might also confer osteoinductive properties to these particles. We show here that blood clotted around BCP microparticles constitutes a cohesive, moldable, and adaptable biomaterial that can be easily implanted in subcutaneous sites but also inserted and maintained in segmental bone defects, conversely to BCP microparticles alone. Moreover, implantation in bony and ectopic sites revealed that this composite biomaterial has osteogenic properties. It is able to repair a 6-mm critical femoral defect in rat and induced woven bone formation after subcutaneous implantation. Parameters such as particle size and loading into the clot are critical for its osteogenic properties. In conclusion, this blood/BCP microparticle composite is a moldable and osteoinductive biomaterial that could be used for bone defect filling in dental and orthopedic surgery.