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Description
Abstract
Introduction
Osteosarcoma (OS), the most common malignant bone tumor, poses significant clinical challenges due to its aggressive progression and limited therapeutic options for metastatic disease[1]. Current preclinical models fail to replicate the mechanical and biochemical complexity of the bone microenvironment[2]. This study explores melt electrowriting (MEW) technology to fabricate polycaprolactone (PCL) scaffolds with optimized geometries and calcium phosphate (CaP) coatings, aiming to create a physiologically relevant model for patient-derived osteosarcoma cell culture.
Methods
PCL scaffolds with rectangular, triangular, and hexagonal geometries were produced using MEW (Fig. 1A,B). Two distinct CaP coating approaches were evaluated: cell-mediated mineralization using SaOS-2 cells and direct calcium phosphate cement (CPC) coating (Fig. 1C). Mechanical properties were characterized via tensile testing, while mineralization efficiency was assessed through calcium quantification (Fig. 1D). Scaffolds were analyzed for their ability to mimic the bone microenvironment by examining calcium deposition and mechanical performance.
Results
Hexagonal scaffolds exhibited superior mechanical performance with tensile strength of 269.9 ± 49.61 kPa, significantly better than triangular (221.4 ± 43.57 kPa) and rectangular (174.7 ± 42.63 kPa) structures. In terms of calcium deposition, hexagonal scaffolds achieved 3.913 ± 0.129 mmol/L in cell culture and 3.933 ± 0.114 mmol/L under CPC coating. For rectangular scaffolds, the cell-coated group showed the highest tensile strength (175.5 ± 35.73 kPa), significantly higher than the uncoated group (160.7 ± 49.92 kPa, p < 0.05) and the CPC-coated group (141.2 ± 18.94 kPa, p < 0.01). Triangular scaffolds demonstrated the best performance in the CPC-coated group (251.0 ± 44.34 kPa), significantly higher than the uncoated group (214.7 ± 43.62 kPa, p < 0.05) and the cell-coated group (231.8 ± 41.92 kPa, p < 0.05). Hexagonal scaffolds showed small differences in tensile strength among the three groups, with the cell-coated group (282.8 ± 45.62 kPa) slightly higher than the CPC-coated group (271.6 ± 32.71 kPa) and the uncoated group (269.0 ± 50.41 kPa). In the cell-cultured scaffolds, the mean calcium contents were hexagonal (3.913 ± 0.129 mmol/L), triangular (3.818 ± 0.182 mmol/L), and rectangular (3.738 ± 0.194 mmol/L) structures. For the CPC-coated scaffolds, the mean calcium contents were hexagonal (3.933 ± 0.114 mmol/L), triangular (3.808 ± 0.228 mmol/L), and rectangular (3.831 ± 0.219 mmol/L). Hexagonal scaffolds performed excellently, triangular scaffolds also showed good results, while rectangular scaffolds require optimization.
Discussion
The findings highlight the potential of hexagonal scaffolds to replicate the bone microenvironment, offering a promising platform for advancing osteosarcoma research and preclinical drug testing. Triangular scaffolds, with balanced mechanical and biochemical properties, represent a flexible option requiring both stability and bioactivity. Although rectangular scaffolds exhibited weaker performance, their straightforward design offers room for enhancement. Future research should focus on refining scaffold geometries and coating strategies to meet the diverse requirements of modeling the osteosarcoma microenvironment and improve translational utility.
References
1.Chiappetta C,et al. Whole-Exome Analysis and Osteosarcoma: A Game Still Open. International Journal of Molecular Sciences. 2024;25(24):13657.
2.Frankenbach-Désor T, et al. Tissue-engineered patient-derived osteosarcoma models dissecting tumour-bone interactions. Cancer and Metastasis Reviews. 2024;44(1).
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