Calcium phosphate coating enhances osteointegration of melt electrowritten scaffold by regulating macrophage polarization

Abstract

The osteoimmune microenvironment induced by implants plays a significant role in bone regeneration. It is essential to efficiently and timely switch the macrophage phenotype from M1 to M2 for optimal bone healing. This study examined the impact of a calcium phosphate (CaP) coating on the physiochemical properties of highly ordered polycaprolactone (PCL) scaffolds fabricated using melt electrowritten (MEW). Additionally, it investigated the influence of these scaffolds on macrophage polarization and their immunomodulation on osteogenesis. The results revealed that the CaP coated PCL scaffold exhibited a rougher surface topography and higher hydrophilicity in comparison to the PCL scaffold without coating. Besides, the surface morphology of the coating and the release of Ca2+ from the CaP coating were crucial in regulating the transition of macrophages from M1 to M2 phenotypes. They might activate the PI3K/AKT and cAMP-PKA pathways, respectively, to facilitate M2 polarization. In addition, the osteoimmune microenvironment induced by CaP coated PCL could not only enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro but also promote the bone regeneration in vivo. Taken together, the CaP coating can be employed to control the phenotypic switching of macrophages, thereby creating a beneficial immunomodulatory microenvironment that promotes bone regeneration. Graphical abstract

Melatonin and calcium phosphate crystal-loaded poly(l-lactic acid) porous microspheres reprogram macrophages to improve bone repair

“…These factors may have activated the PI3K/AKT and cAMP-PKA pathways, promoting macrophage M2 polarization. 44 Research by Sun et al identified a calcium phosphate-mediated environment rich in PO 4 3− . Extracellular PO 4 3− is transported into the cytoplasm via the sodium-dependent phosphate transporter 1, participating in the tricarboxylic acid cycle and oxidative phosphorylation to generate energy in the form of ATP.…”