Quick-forming hydroxyapatite/agarose gel composites induce bone regeneration

We investigated the fundamental properties of quick-forming hydroxyapatite (HAp)/agarose gel composites, and evaluated their potential as an injectable bone substitute. From scanning electron microscope observations, the HAp/agarose gel composites produced by an innovative electrophoretic process showed an interconnecting structure with the HAp particles. The diameter of the HAp particles was roughly 1 microm, and the total amount of HAp particles was estimated by a quantification of the calcium ions. In the case of 1 mg of dry composite, 10 microg of HAp was formed in the agarose gel. Moreover, X-ray diffraction analysis revealed that the HAp particles had an amorphous structure, so the HAp particles were expected to dissolve under physiological conditions relative to the HAp with higher crystallinity. The advantages of the resultant HAp/agarose gel composites are ease of handling, close contact with the surrounding tissues, and ease of use as an injectable material. As a preliminary animal study, the composites were implanted into the medial femoral condyle of rabbits. After implantation, the process of bone regeneration was evaluated by microfocus-computed tomography (microCT) and histological analysis. At 2 weeks postoperatively, newly-formed bone was observed at the edge of the bone defect site, and at 4 weeks postoperatively, excellent bone regeneration was observed. The implanted composite gradually degraded, and disappeared at 8 weeks postoperatively. This result indicated that the composite dissolved rapidly, and was replaced by newly-formed bone. Quick-forming HAp/agarose gel composites may be a good candidate as an injectable biomaterial, particularly in the fields of orthopedic, oral, and maxillofacial surgery.