Machine Learning-Assisted Development of Injectable, Mechanically Robust, and Energy Metabolism-Modulating Brushite Cements.

Journal: Research (Washington, D.C.)
Published Date: Jul 10, 2025

Abstract

In orthopedic minimally invasive surgeries (MIS) such as percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP), calcium phosphate cements (CPCs) are an attractive alternative to bioinert polymethyl methacrylate (PMMA) due to their superior biocompatibility and osteoconductivity. However, the mechanical strength and injectability of CPCs often remain insufficient for load-bearing applications, limiting their broader use in these critical procedures. To address this challenge, we introduce a machine learning-assisted approach to enhance both the mechanical strength and injectability of CPCs by identifying specific polymers as superplasticizers. By optimizing its concentration and the liquid-to-powder (L/P) ratio, we developed an injectable brushite-based cement with an exceptional compressive strength of 79.5 ± 4.3 MPa, surpassing both traditional CPCs and PMMA in orthopedic applications. Zeta potential and adsorption studies reveal that these superplasticizers enhance cement paste dispersion via electrostatic repulsion. In vitro assays demonstrate excellent biocompatibility and osteogenic properties, while in vivo experiments further confirm the cement's superior osteoinductive capability. The brushite cement regulates cellular metabolism and stem cell differentiation by enhancing energy metabolism and activating key signaling pathways such as phosphatidylinositol 3-kinase-AKT and mitogen-activated protein kinase-extracellular signal-regulated kinase. These findings offer a novel approach to fabricating CPCs with enhanced mechanical strength and osteogenic potential, addressing long-standing challenges in orthopedic MIS.

Authors

  • Dachuan Liu
    Orthopedic Institute, Department of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, China.
  • Jiaxu Shi
    Orthopedic Institute, Department of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, China.
  • Youhao Ni
    Key Laboratory of Concrete and Prestressed Concrete Structures of Ministry of Education, Southeast University, Nanjing 210096, China.
  • Li Dong
    Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China. donglikn199@163.com.
  • Chen Cui
    Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
  • Lijie Wang
    Department of Occupational and Environmental Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
  • Yu Zhang
    College of Marine Electrical Engineering, Dalian Maritime University, Dalian, China.
  • Jingxi Xu
    Orthopedic Institute, Department of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, China.
  • Weicheng Chen
    Orthopedic Institute, Department of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, China.
  • Kai Lu
    College of Computer, National University of Defense Technology, China.
  • Miodrag J Lukic
    Laboratory of Physics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
  • Wei Xia
    Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Song Chen
    Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China.
  • Bin Li
    Department of Magnetic Resonance Imaging (MRI), Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

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