In vitro and in vivo assessment of CaP materials for bone regenerative therapy. The role of multinucleated giant cells/osteoclasts in bone regeneration

In this work, bone formation/remodeling/maturation was correlated with the presence of multinucleated giant cells (MGCs)/osteoclasts (tartrate‐resistant acid phosphatase [TRAP]‐positive cells) on the surface of beta‐tricalcium phosphate (β‐TCP), sintered deproteinized bovine bone (sDBB), and carbonated deproteinized bovine bone (cDBB) using a maxillary sinus augmentation (MSA) in a New Zealand rabbit model. Microtomographic, histomorphometric, and immunolabeling for TRAP‐cells analyses were made at 15, 30, and 60 days after surgery. In all treatments, a faster bone formation/remodeling/maturation and TRAP‐positive cells activity occurred in the osteotomy region of the MSA than in the middle and submucosa regions. In the β‐TCP, the granules were rapidly reabsorbed by TRAP‐positive cells and replaced by bone tissue. β‐TCP enabled quick bone regeneration/remodeling and full bone and marrow restoration until 60 days, but with a significant reduction in MSA volume. In cDBB and sDBB, the quantity of TRAP‐positive cells was smaller than in β‐TCP, and these cells were associated with granule surface preparation for osteoblast‐mediated bone formation. After 30 days, more than 80% of granule surfaces were surrounded and integrated by bone tissue without signs of degradation, preserving the MSA volume. Overall, the materials tested in a standardized preclinical model led to different bone formation/remodeling/maturation within the same repair process influenced by different microenvironments and MGCs/osteoclasts. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:282–297, 2020.