摘要
The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.
基金
The authors would like to thank Li LI and H.Z.Xie for the technical support.This work was financially supported by the National Natural Science Foundation of China(Nos.82002303 and 81702171)
the Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515011536,2021A1515220093,2021A1515220086,2019A1515111156,and 2022A1515011815)
the Scientific Research Foundation of Peking University Shenzhen hospital(No.KYQD2021064)
the Health and Medical Research Fund(No.19180712)
the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(No.201806081018272960)
the Shenzhen Science and Technology Innovation Committee Projects(Nos.JCYJ20190809182213535 and JSGG20180507183242702)
the program from Shanghai Municipal Health Commission(No.201740165)
the National Key R&D Program of China(No.2018YFC1105100)
the Hong Kong Innovation Technology Fund(Nos.ITS/287/17 and ITS/405/18)
the Hong Kong Research Grant Council General Research Fund(No.17214516).