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

Shenglong Tan; Yifan Wang; Yingying Du; Yin Xiao; Shengmin Zhang

doi:10.1016/j.bioactmat.2021.03.006

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

Bioact Mater. 2021 Mar 19;6(10):3411-3423. doi: 10.1016/j.bioactmat.2021.03.006. eCollection 2021 Oct.

Authors

Shenglong Tan^{1

2

3}, Yifan Wang^{1

2

3}, Yingying Du^{1

2

3}, Yin Xiao^{4

5}, Shengmin Zhang^{1

2

3}

Affiliations

¹ Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China.
² Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
³ Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan, 430074, China.
⁴ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland, 4059, Australia.
⁵ Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland, 4059, Australia.

Abstract

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.

Keywords: Anti-inflammation; Immunomodulation; Injectable bone cement microsphere; Mg; Osteogenesis.