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Peer-reviewedCC BYStem Cell Research & Therapy

Regulatory mechanism of stem cell scaffold porosity and stiffness on the processes of intramembranous ossification and bone regeneration

  1. 1Third Affiliated Hospital of Zhejiang Chinese Medical University
  2. 2Arthritis Clinic and Research Center, Peking University People’s Hospital, Peking University
  3. 3Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University

Abstract

Bone defects remain a significant clinical challenge due to the limited regenerative capacity. Biomaterials can offer effective therapeutic approaches to address this challenge, where their physical properties play a critical role in determining the success of regeneration. Here, we fabricated cryogelated 3D porous scaffolds with independently controlled pore sizes and stiffness. These scaffolds were then seeded separately with bone marrow stromal cells (BMSCs) and MLO-A5 cells to create osteogenic cell-scaffold composites. To determine the optimal physical properties for promoting bone regeneration, we evaluated the scaffolds using both in vitro osteogenic cultures and a rat critical-sized calvarial defect model. Transcriptomic analysis was performed concurrently to explore the molecular link between physical scaffold cues and osteogenic differentiation. The results indicated that the small-pore high-stiffness scaffold exhibited the optimal osteogenic performance in vitro. In rats, the small pore scaffold groups also showed superior bone regeneration. Furthermore, transcriptomic analysis revealed that scaffold pore size significantly changed the expression of Apolipoprotein E (ApoE) and Osteoglycin (OGN). Our findings suggest a feasible strategy to enhance the efficiency of bone regeneration by leveraging the properties of tailored scaffolds, enabling personalized repair approaches.

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BibTeX
@article{chen2026regulatory,
  title = {{Regulatory mechanism of stem cell scaffold porosity and stiffness on the processes of intramembranous ossification and bone regeneration}},
  author = {Qianqian Chen and Shichun Xu and Yiqi Su and Sengyang Xiao and Qingchen Meng and Wenjing Li and Yunwei Wang and Dan Xing and Hui Li},
  journal = {Stem Cell Research \& Therapy},
  year = {2026},
  month = jul,
  doi = {10.1186/s13287-026-05170-7},
  url = {https://doi.org/10.1186/s13287-026-05170-7},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Regulatory mechanism of stem cell scaffold porosity and stiffness on the processes of intramembranous ossification and bone regeneration
AU  - Qianqian Chen
AU  - Shichun Xu
AU  - Yiqi Su
AU  - Sengyang Xiao
AU  - Qingchen Meng
AU  - Wenjing Li
AU  - Yunwei Wang
AU  - Dan Xing
AU  - Hui Li
PY  - 2026
DA  - 2026/07/01
JO  - Stem Cell Research & Therapy
DO  - 10.1186/s13287-026-05170-7
UR  - https://doi.org/10.1186/s13287-026-05170-7
AB  - Bone defects remain a significant clinical challenge due to the limited regenerative capacity. Biomaterials can offer effective therapeutic approaches to address this challenge, where their physical properties play a critical role in determining the success of regeneration. Here, we fabricated cryogelated 3D porous scaffolds with independently controlled pore sizes and stiffness. These scaffolds were then seeded separately with bone marrow stromal cells (BMSCs) and MLO-A5 cells to create osteogenic cell-scaffold composites. To determine the optimal physical properties for promoting bone regeneration, we evaluated the scaffolds using both in vitro osteogenic cultures and a rat critical-sized calvarial defect model. Transcriptomic analysis was performed concurrently to explore the molecular link between physical scaffold cues and osteogenic differentiation. The results indicated that the small-pore high-stiffness scaffold exhibited the optimal osteogenic performance in vitro. In rats, the small pore scaffold groups also showed superior bone regeneration. Furthermore, transcriptomic analysis revealed that scaffold pore size significantly changed the expression of Apolipoprotein E (ApoE) and Osteoglycin (OGN). Our findings suggest a feasible strategy to enhance the efficiency of bone regeneration by leveraging the properties of tailored scaffolds, enabling personalized repair approaches.
SN  - 1757-6512
ER  -