Time-Course Evaluation of the In Vivo Resorption Process of Calcium Phosphates/Poly(lactide-co-glycolide) Composites Using Radiological Imaging and Histology

There has been much development of composites of calcium phosphate and polymers for use as artificial bone, with other applications still ongoing, and clarification of the in vivo absorption mechanism is considered an important perspective. In order to clarify the absorption mechanism of bioabsorbable materials used for artificial bones and bone grafts, we prepared composites of calcium phosphate and polymers and conducted in vivo experiments in experimental animals using composites as implantation samples. Two typical types of calcium phosphate, β-tricalcium phosphate (β-TCP) and unsintered hydroxyapatite (uHA), were used as calcium phosphate, and copolymers of poly-dl-lactide-<i>co</i>-glycolide (PDLGA) and poly-l-lactide-<i>co</i>-glycolide (PLGA) were used as polymers. For samples composed of PDLGA and calcium phosphates, the weight ratios of calcium phosphate were set at 40% and 10% for uHA and 40% for β-TCP (uHA(40), uHA(10) and β-TCP(40), respectively). A composite sample of PLGA and uHA was also prepared with a weight ratio of 10% uHA (uHA(10)/PLGA), intending slow degradation of the polymer matrix compared to PDLGA. The samples were implanted in the metaphysis and diaphysis region of rabbits' femur for up to 48 weeks. In this study, positron emission tomography/X-ray computed tomography (PET/CT) was used to continuously evaluate the changes in the samples and the accumulation of cells in the animals, and histological evaluation was performed, focusing on the time of characteristic changes in the PET/CT to confirm the cell types. The results are summarized as follows: (1) the absorption mechanism of the materials used in this study was suggested to be mainly phagocytosis by macrophages; (2) the disappearance rate was faster for β-TCP(40) compared with uHA(40); and (3) uHA(10), having a lower proportion of uHA, is not prone to aggregation and exhibited a similar disappearance result to β-TCP(40). These results suggest that phagocytosis by macrophages is the dominant path in resorption of the bioresorbable materials, and the resorption period varies depending on the type of polymer. It is important to optimize the type and amount of polymers and calcium phosphate in order to achieve a degradation rate of bioresorbable materials that corresponds to the extent of damage in the healing area.