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Updated: Oct 21, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
3D-printing magnesium-polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating
Weilin Zhang1, Wei Zhao1, Qin Li2
1Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning, China.
Abstract:
Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium-polycaprolactone (Mg-PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg-PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg-PCL scaffold as well as melatonin-loaded Mg-PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg-PCL-MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg-PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg-PCL-MT could be a potential therapeutics for OS.
Insights
Melatonin-loaded scaffolds target cell-in-cell structures in osteosarcoma (OS) by inhibiting the Rho/ROCK pathway. This novel therapeutic approach effectively reduces OS proliferation, invasion, and metastasis.
Area of Science:
- Biomaterials Engineering
- Oncology Research
- Molecular Biology
Background:
- Osteosarcoma (OS) exhibits increased cell-in-cell (CIC) structures, linked to altered tumor cell metabolism.
- Melatonin, a potential anticarcinogen, has a short half-life, limiting its therapeutic use.
- Melatonin receptor 1 (MT1) and CIC expressions are elevated in OS tissues and cells.
Purpose of the Study:
- To develop and evaluate a melatonin-loaded 3D printed magnesium-polycaprolactone (Mg-PCL) scaffold for osteosarcoma treatment.
- To investigate the molecular mechanisms by which melatonin affects CIC structures and OS progression.
- To assess the efficacy of the melatonin-loaded scaffold in inhibiting OS metastasis.
Main Methods:
- Fabrication and characterization of 3D printed Mg-PCL scaffolds.
- In vitro and in vivo studies to assess the effects of Mg-PCL and melatonin-loaded Mg-PCL (Mg-PCL-MT) on OS cells.
- Investigation of the molecular pathways involved, including Rho/ROCK and cAMP/PKA signaling.
Main Results:
- Melatonin treatment inhibited the CIC pathway via the cAMP/PKA signaling pathway, affecting mitochondrial physiology.
- The Mg-PCL-MT scaffold demonstrated significant inhibition of OS cell proliferation, invasion, and metastasis in vivo.
- Elevated MT1 and CIC expressions were observed in OS tissues and cells.
Conclusions:
- Melatonin-loaded Mg-PCL scaffolds effectively inhibit osteosarcoma progression by targeting the CIC pathway.
- The Mg-PCL-MT scaffold shows potential as a novel therapeutic strategy for osteosarcoma, reducing metastasis.
- This approach interferes with tumor cell energy metabolism and exhibits anti-invasion and anti-metastasis properties.
