Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation

Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects. Amongst different kinds of injectable bone cements, bioactive calcium phosphate bone cement (CPC) has been widely studied due to its biological activity. However, its dense structure and poor biodegradability prevent the ingrowth of living tissue, which leads to undesirable bone regeneration and clinical translation. To address this issue, we prepared bone cement based on Magnesium-containing microspheres (MMSs) that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth. Interestingly, magnesium ions released from MMSs cement (MMSC) trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206, which is beneficial to osteogenesis. Moreover, the physicochemical properties of MMSC, including heat release, rheology and setting time, can be tuned to meet the requirements of injectable bone cement for clinical application. Using a rat model, we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation. The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures, biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.