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To address the issue of limited repair efficiency of key segmental bone defects in an aged microenvironment, a new type of three-layer bone membrane carrying extracellular vesicles from juvenile fracture sources was constructed. This material can achieve epigenetic reprogramming through DNA methylation, remodel the aged bone microenvironment, reverse the senescent phenotype of bone marrow mesenchymal stem cells, and regulate the bone immune microenvironment. When combined with a 3D printing scaffold, it can effectively promote bone defect regeneration in aged animals and clearly identify Foxo3 as the core regulatory factor in this process, providing new material and mechanism research ideas for the repair of aged bone tissue.
01 Research Background
The aged bone microenvironment significantly inhibits the repair process of key segmental bone defects, often resulting in poor repair outcomes. Traditional bone repair materials mainly focus on structural support, but are difficult to effectively intervene in the aging-related bone microenvironment and balance mechanical adaptability and biological regulatory functions. There are still key scientific issues to be addressed for the repair of aged bone defects.
02 Main Content
Develop a three-layer structure bone membrane with epigenetic reprogramming capability, carrying extracellular vesicles from juvenile mouse fractures; explore the regulatory effects of this material on the senescent phenotype and osteogenic differentiation of aged bone marrow mesenchymal stem cells, and analyze its impact on macrophage polarization and osteoclast generation; verify the bone regeneration effect of the bone membrane combined with a 3D printing scaffold in the key segmental bone defect model of aged animals; analyze the molecular mechanism of the material remodeling the aged bone microenvironment at the DNA methylation level, and screen the core regulatory genes.
03 Research Design
Design a three-layer structure bone membrane as a carrier, load extracellular vesicles from juvenile fracture sources, and prepare functionalized bone repair materials; through in vitro experiments, detect the effects of the material on aging-related indicators of bone marrow mesenchymal stem cells, osteogenic differentiation ability, and its regulatory effects on bone immune-related cells; construct a key segmental bone defect model of the femur in aged mice, and combine the functionalized bone membrane with a 3D printing scaffold for implantation, observing the structural integrity and bone regeneration of the repair area; use bisulfite sequencing to analyze the DNA methylation modification pattern, and explore the epigenetic regulatory mechanism and key regulatory genes.
1. Journal: Bioactive Materials (IF: 20.3)
2. Publication Date: March 27, 2026
3. DOI: 10.1016/j.bioactmat.2026.03.036 4. Authors: Jiaqian Zheng, Junhua Ke, Shiyu Wu, Yang Lan, Zhouhua Zhong, Siyuan Yang, Naru Zhao, Zhen Wang, Muyuan Chai, Xuetao Shi, Yingjun Wang
