Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33811079.
- Also identified by DOI 10.1126/sciadv.abf6654 and PMC identifier 11060047.
- Licence recorded as CC BY-NC.
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Abstract
Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO<sub>2</sub> structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO<sub>2</sub> structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, <i>interleukin-4</i>, and <i>interleukin-10</i> and released the highest amount of <i>bone morphogenetic protein-2</i> among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO<sub>2</sub> honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (<i>RhoA, Rac1, and CDC42</i>), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.