@article{Liu2026, 
author = {Shubo Liu and Qinghua Chen and Yaowen Xu and Haidong Yu and Jue Cao and Zichu Ding and Weixin Zheng and Keyu Chen and Yuexin Zhao and Yan Shi and Shaoxiong Min and Ben Wang and Jie Shen and Bin Chen},
title = {Magnesium-containing composite hydrogel scaffolds with immunomodulatory and osteogenic dual effects enhance bone defect repair via CD4+ T cells modulation},
year = {2026},
journal = {Journal of Magnesium and Alloys},
volume = {15},
number = {C},
keywords = {Osteo-immunomodulation, Composite, Magnesium ion, T cell, Bone repair},
url = {https://www.sciopen.com/article/10.1016/j.jma.2025.07.020},
doi = {10.1016/j.jma.2025.07.020},
abstract = {The clinical challenges of bone defect repair have driven the exploration of novel biomaterials with immunomodulatory and osteogenic functionalities. While previous studies predominantly focused on macrophages in the osteoimmune microenvironment, the regulatory mechanisms of T cells, particularly "conductor" CD4+ T cells, remain poorly understood. This study investigated the effects of magnesium ions (Mg2+) on CD4+ T cell polarization and their mediated bone regeneration using Mg2+-functionalized composite materials. Results demonstrated that suitable Mg2+ concentration range significantly enhanced CD4+ T cell activation and proliferation, promoting polarization toward Th1 and Treg subtypes, thereby establishing a pro-inflammatory and anti-inflammatory synergistic immune microenvironment. Conditioned medium experiments further confirmed that cytokines secreted from CD4+ T cells synergized with Mg2+ to augment alkaline phosphatase activity and calcium deposition in bone marrow mesenchymal stem cells (MSCs), while mitigating the inhibitory effects of high Mg2+ concentrations on osteogenesis. Then, nano-magnesium oxide-doped polycaprolactone scaffolds (Mg-PCL) and T cell activator-crosslinked magnesium-alginate hydrogels (T-Mg-Gel) were engineered to control the release of Mg2+. In vivo evaluations revealed that 1%Mg-PCL scaffolds facilitated membranous ossification in cranial defects via sustained Mg2+ release, whereas T-Mg-Gel accelerated bone regeneration by suppressing early-stage inflammation and promoting long-term Treg cell regulation. This study revealed the pivotal role of CD4+ T cells in osteoimmunology and provides a novel strategy for designing intelligent bone repair materials with dual immunomodulatory and osteogenic capabilities.}
}