Immediately upon implantation, scaffolds for bone repair are exposed to the patient's blood.
Blood proteins adhere to the
biomaterial surface and the
protein layer affects both blood cell functions and
biomaterial bioactivity. Previously, we reported that 80-200 µm
biphasic calcium phosphate (BCP) microparticles embedded in a
blood clot, induce ectopic woven bone formation in mice, when 200-500 µm BCP particles induce mainly fibrous tissue. Here, in a LC-MS/MS proteomic study we compared the differentially expressed
blood proteins (plasma and blood cell
proteins) and the deregulated signaling pathways of these osteogenic and fibrogenic blood composites. We showed that blood/BCP-induced osteogenesis is associated with a higher expression of
fibrinogen (FGN) and an upregulation of the Myd88- and NF-κB-dependent TLR4 signaling cascade. We also highlighted the key role of the LBP/CD14
proteins in the TLR4 activation of blood cells by BCP particles. As FGN is an endogenous
ligand of TLR4, able to modulate blood composite stiffness, we propose that different FGN concentrations modify the
blood clot mechanical properties, which in turn modulate BCP/blood composite osteoactivity through TLR4 signaling. The present findings provide an insight at the
protein level, into the mechanisms leading to an efficient bone reconstruction by blood/BCP composites. STATEMENT OF SIGNIFICANCE: Upon implantation, scaffolds for bone repair are exposed to the patient's blood.
Blood proteins adhere to
bone substitute surface and this
protein layer affects both
biomaterial bioactivity and bone healing. Therefore, for the best outcome for patients, it is crucial to understand the molecular interactions between blood and bone scaffolds.
Biphasic calcium phosphate (BCP) ceramics are considered as the gold standard in bone reconstruction surgery. Here, using proteomic analyses we showed that the osteogenic properties of 80-200 µm BCP particles embedded in a
blood clot is associated with a higher expression of
fibrinogen.
Fibrinogen upregulates the Myd88- and NF-κB-dependent TLR4 pathway in blood cells and, BCP-induced TLR4 activation is mediated by the LBP and CD14
proteins.