Effect and mechanism of a concentration-dependent inorganic ion biomimetic periosteum in a repairing bone defect

An inorganic ion functionalized biomimetic periosteum constitutes a new strategy for the design and application of new bone repair materials. However, the effect of cumulative concentration of inorganic ions (e.g. inorganic ion (Si4+)) on bone immune microenvironment in promoting bone repair is still unclear. Here, we used different mesoporous bioactive glass nanoparticles (MBGNs) contents and a methacrylic acid gelatin (GelMA) organic-inorganic double crosslinking techniques to construct low, medium, and high content inorganic ion bio-mimetic periosteum. As the inorganic ion concentration increased, the compression modulus of LM@G, MM@G, and HM@G (1, 3, and 5 wt% MBGNs, respectively) was 1.6, 3.2, and 2.1 times higher than that of the GelMA hydrogel and the Si4+ release was 35.4 +/- 0.4, 59.5 +/- 0.2, and 71.5 +/- 1.2 ppm in vitro, respectively. The ERK1/2 and p65 inhibition in the HM@G was 51.9% and 40.2% higher than that in the LM@G; however, the stem cell recruitment was about 85.2% lower than that in the LM@G, and the vascular germination degree was 35.4% lower than that in the MM@G. Contradiction between immune regulation and bone repair was found. However, the anti-inflammation in the MM@G was 30.8%, 30.1% higher than that in the LM@G, and stem cell recruitment and vascular sprouting were 3.4 and 1.6 times higher, respectively than those in the HM@G. In summary, the anti-inflammatory effect of MM@G group is stronger than that of LM@G group, and the effect of stem cell recruitment is more significant than that of HM@G group. We not only explore the biological mechanism of Si4+ coordinating macrophages and stem cells to promote bone repair, but also provide research basis for designing inorganic ion based immunofunctional biomaterials.