Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification

Jie Shen; Bo Chen; Xinyun Zhai; Wei Qiao; Shuilin Wu; Xuanyong Liu; Ying Zhao; Changshun Ruan; Haobo Pan; Paul K Chu; Kenneth M C Cheung; Kelvin W K Yeung

doi:10.1016/j.bioactmat.2020.08.025

Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification

Bioact Mater. 2020 Sep 10;6(2):503-519. doi: 10.1016/j.bioactmat.2020.08.025. eCollection 2021 Feb.

Authors

Jie Shen^{1

2}, Bo Chen^{1

3}, Xinyun Zhai⁴, Wei Qiao^{1

2}, Shuilin Wu^{5

6}, Xuanyong Liu^{7

8}, Ying Zhao⁹, Changshun Ruan⁹, Haobo Pan⁹, Paul K Chu¹⁰, Kenneth M C Cheung^{1

2}, Kelvin W K Yeung^{1

2}

Affiliations

¹ Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China.
² Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, Department of Orthopaedics and Traumatology, the University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
³ Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ School of Materials Science and Engineering, Nankai University, Tianjin, China.
⁵ School of Materials Science & Engineering, the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin, China.
⁶ Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan, China.
⁷ State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China.
⁸ Cixi Center of Biomaterials Surface Engineering, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Ningbo, China.
⁹ Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
¹⁰ Department of Physics, Department of Materials Science & Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.

Abstract

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg²⁺) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg²⁺ content niche (~4.11 mM) led to superior bone regeneration, while Mg²⁺-free and strong Mg²⁺ content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg²⁺ cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.

Keywords: 3D scaffold; Bone tissue regeneration; Magnesium ion; Microenvironment; Nanocomposite.