2. Academic Validation
  3. Three-Dimensional Bioprinted Scaffolds Loaded with Multifunctional Magnesium-Based Metal-Organic Frameworks Improve the Senescence Microenvironment Prompting Aged Bone Defect Repair

Three-Dimensional Bioprinted Scaffolds Loaded with Multifunctional Magnesium-Based Metal-Organic Frameworks Improve the Senescence Microenvironment Prompting Aged Bone Defect Repair

  • ACS Nano. 2025 Jun 24;19(24):22141-22162. doi: 10.1021/acsnano.5c03023.
Xin Sun 1 2,  Xiang Xu 1 3,  Xue Zhao 4,  Jie Ma 1,  Tianchang Wang 1,  Xiaokun Yue 1,  Xueheng Sun 5,  Xiaojun Li 1,  Xiaojiang Sun 1 6,  Weijiao Zhang 7,  Kai Zhang 1,  Deteng Zhang 8,  Xin Zhao 1,  Wenjie Jin 1,  Jinwu Wang 1
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, China.
  • 2 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China.
  • 3 School of Energy Science and Engineering, Central South University, No. 932 South Lushan Road, Changsha ,Hunan 410083, China.
  • 4 Department of Radiology,Huangpu Branch of Shanghai Ninth People's Hospital, affiliated to Shanghai Jiao Tong University, No. 58 Puyu East Road, Shanghai 200010, China.
  • 5 Department of Sport Rehabilitation, Shanghai University of Sport, No. 399 Changhai Road, Shanghai 200438, China.
  • 6 Department of Orthopaedics Surgery, Fengcheng Hospital of Fengxian District, Shanghai, No. 9983 Chuannanfeng Road, Shanghai 201411, China.
  • 7 School of Life Science and Technology, ShanghaiTech University, No. 393 Huaxia Middle Road, Shanghai 201210, China.
  • 8 Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, No. 308 Ningxia Road, Qingdao, Shandong 266071, China.
PMID: 40509557 DOI: 10.1021/acsnano.5c03023
Abstract

Age-related bone defects cause disability and mortality in older individuals. During bone repair in older individuals, high oxidative stress and excessive inflammation in the senescent microenvironment (SME) lead to bone marrow mesenchymal stem cell (BMSC) senescence, thereby affecting bone regeneration. In this study, we prepared multifunctional magnesium (Mg) and cerium (Ce) ion-based metal-organic frameworks (MOFs) using a hydrothermal method and constructed a three-dimensional (3D) bioprinted scaffold to effectively scavenge Reactive Oxygen Species (ROS) and sustainably release Mg2+ to improve the SME and age-related bone defect repair. Under oxidative stress, the scaffolds delayed the senescence of loaded BMSCs and promoted M2 macrophage polarization of RAW264.7 cells, further improving BMSC osteogenic differentiation. In addition, Mg2+ release promoted aldehyde dehydrogenase 3A1 expression through the activation of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway, thereby delaying BMSC senescence. Adding the Wnt/β-catenin agonist SKL2001 to the scaffolds further enhanced these effects. Finally, the composite scaffolds accelerated the repair of critical-sized calvarial defects in an aged rat model. In summary, these results demonstrated the value of improving the SME for delaying BMSC senescence using multifunctional Mg-Ce-MOF and SKL2001-based 3D-bioprinting scaffolds, thereby providing an effective strategy for promoting age-related bone defect repair.

Keywords

3D-bioprinting; age-related bone defect repair; bone marrow mesenchymal stem cell senescence; metal−organic framework; reactive oxygen species.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101085
    99.68%, Wnt/β-catenin Pathway Agonist