Effect of biocomposite mediated magnesium ionic micro-homeostasis on cell fate regulation and bone tissue regeneration

Bioinorganic cations, that actively involved in many vital cellular activities, have been highlighted in regeneration and repair of tissues recently. However, researchers are still exploring how the sophisticated regulation of these bioactive factors within the microenvironment contribute to the process. Here, we established magnesium oxide homogeneously- and heterogeneously-embedded biocomposites to investigate the biological impacts that result from the different aggregation structure of the bioinorganic element. On the heterogeneous biocomposite, unbalanced microenvironment with erratic ion niche was provided, while stable ionic microenvironment was shown on the homogeneous biocomposite. Compared with the ionic micro-homeostasis, the heterogeneous micron-cluster-created unbalanced niche compromised cellular adhesion and proliferation by restraining the membrane extensions and downregulating the expression of proliferative genes. This unbalanced niche also motivated nonactivated macrophage polarized towards pro-inflammatory phenotype and induced high ratio of necrotic cell death by increasing the intracellular oxidative stress and decreasing the ATP content. After implantation, the homogeneous scaffold promoted tissue healing, whereas the immune responses were deteriorated and prolonged by heterogeneous scaffold, which leading to impaired bone regeneration. This study demonstrated the importance of biocomposite-established magnesium ionic micro-homeostasis on bone tissue regeneration and may inspires the future development of biomaterials.