Table 1.
Implication of macrophages and osteoclasts in the bone formation induced by calcium phosphate biomaterials.
| CaP biomaterial | In vitro and in vivo models | Outcome | References |
|---|---|---|---|
| Hydroxyapatite (HA) | In vitro: Osteoclasts (OCs) were differentiated from bone marrow monocytes from C57BL/6 mice. Primary osteoblasts (OBs) were derived from the calvaria. Ex vivo: Organ culture of explanted calvaria. In vivo model: C57BL/6mice | CTHRC1 protein is secreted by mature OCs. CTHRC1 mRNA expression is elevated in OCs cultured on HA compared to tissue culture plastic (TCP). CTHRC1 stimulates osteoblastogenesis (gene expression and mineralized matrix deposition). CTHRC1 expression and bone turnover in vivo was increased by RANKL injections and conversely decreased by alendronate treatment. OC-specific CTHRC1 KO mice led to reduced bone formation and lower bone mass. | (37) |
| Coral derived calcium carbonate (CC)/ HA constructs | In vivo model: Intramuscular implantation in Chacma baboons | Osteoinduction of biomaterials was inhibited by preloading constructs with the bisphosphonate zoledronate. | (38) |
| β-TCP | In vivo model: Intramuscular implantation in female beagle dogs | CaP induces the formation of TRAP and Cathepsin K positive, multinucleated cells on the biomaterial, and their presence precedes ectopic bone formation | (39) |
| β-TCP with different surface microstructures | In vitro: Osteoclasts were differentiated from a murine macrophage cell line RAW264.7 Human MSCs were isolated from bone marrow harvested from femoral heads. In vivo model: Intramuscular implantation in male mongrel dogs | In vitro, CaPs with submicron-scale surfaces lead to increased differentiation of OCs and higher secretions of factors that induced osteogenic differentiation of MSCs. In vivo, submicro-structured CaPs formed bone and OCs presence was significant, whereas micro-structured CaPs formed no bone and OC presence was spare. | (40) |
| β-TCP | In vivo model: Rabbit femoral condyles | Loading of Alendronate (bisphosphonate) onto β-TCP inhibited the presence of TRAP-positive cells on the surface of the biomaterial and abrogated the CaP-mediated bone formation. | (41) |
| β-TCP | In vivo model: FVB/NCrl strain mice | CaPs induced osteoclastogenesis and ectopic bone formation. Depletion of osteoclasts by local injection of liposome-encapsulated clodronate impeded bone formation by CaPs. | (42) |
| Biphasic calcium phosphate (BCP) HA/ β-TCP composite | In vitro: Mouse macrophage cell line RAW264.7. Mouse bone marrow-derived MSCs. | Macrophages upregulated gene expression of inflammatory factors (IL-1, IL-6, MCP-1) and growth factors (EGF, PDGF, and VEGF) as a consequence of their CaP substrate. This macrophage conditioned media (CM) increased MSC migration and osteogenic differentiation (osteogenic gene expression and mineralized matrix deposition). | (43) |
| BCP (HA/ β-TCP) | In vitro: Mouse macrophage cell line RAW264.7. Mouse bone marrow-derived MSCs. In vivo model: Implantation into thigh muscle of male BALB/c mice. | BCP implantation in vivo caused infiltration of macrophages to the site, followed by homing of MSCs and subsequent ectopic bone formation. BMSCs migrated significantly faster under stimulation by CM from macrophages cultured on BCP, compared to CM from macrophages cultured on TCP. Secretion of MCP-1 and MIP- 1α by macrophages was increased by culture on BCP and were shown to be the effectors of enhanced migration since blocking these in macrophage CM had inhibited MSC migration. | (44) |