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Updated: Sep 27, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma
Yixuan Lin1, Yiqi Yang1, Kai Yuan1
1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Abstract:
Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models and tumour spheroids, our 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation. The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway. We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models. We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research, which may contribute to novel therapeutic strategy discovery.
Insights
A novel 3D bioprinted osteosarcoma model incorporating extracellular matrix (ECM) better mimics tumor biology. This advanced model reveals distinct cell behaviors and drug sensitivities, improving osteosarcoma research.
Area of Science:
- Biomedical Engineering
- Oncology
- Extracellular Matrix Research
Background:
- Current in vitro osteosarcoma models (2D cultures, spheroids) lack extracellular matrix (ECM), limiting their pathological relevance.
- Traditional models may not accurately reflect osteosarcoma's in vivo behavior or drug responses.
- There is a need for more physiologically relevant models for osteosarcoma research and drug discovery.
Purpose of the Study:
- To develop and characterize a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that includes an ECM analogue.
- To compare the multi-omics profiles and drug sensitivity of the 3DBPO model against traditional 2D and spheroid models.
- To evaluate the potential of the 3DBPO model for fundamental and translational osteosarcoma research.
Main Methods:
- Fabrication of a 3D bioprinted osteosarcoma model using photo-crosslinkable bioinks (gelatine methacrylamide, hyaluronic acid methacrylate) to mimic tumor ECM.
- Performance of multi-omics analysis, including transcriptomics and DNA methylomics, to compare the 3DBPO model with 2D and spheroid models.
- Assessment of drug sensitivity, particularly for therapies targeting the autophagy pathway.
Main Results:
- The 3DBPO model exhibited significant differences in cell cycle, metabolism, and adherens junction pathways compared to 2D and spheroid models.
- Multi-omics analysis revealed distinct epigenetic regulation patterns in the 3DBPO model.
- The 3DBPO model demonstrated increased sensitivity to therapies targeting the autophagy pathway, suggesting altered metabolic characteristics.
- Simulating ECM in the 3DBPO model resulted in different osteosarcoma cell metabolic profiles and drug sensitivities.
Conclusions:
- The 3D bioprinted osteosarcoma model (3DBPO) provides a more accurate representation of osteosarcoma pathology than traditional models due to the inclusion of ECM.
- The 3DBPO model offers a valuable platform for investigating osteosarcoma cell behavior, epigenetic regulation, and metabolic characteristics.
- This advanced model enhances drug screening by revealing differential drug sensitivities and holds promise for discovering novel therapeutic strategies in osteosarcoma research.
