PDF(Pubmed)
Abstract：
This scoping review evaluated 3D osteosarcoma (OS) models\' biomimicry, examining their ability to mimic the tumour microenvironment (TME) and their drug sensitivity. Adhering to PRISMA-ScR guidelines, the systematic search revealed 293 studies, with 70 selected for final analysis. Overall, 64% of 3D OS models were scaffold-based, compared to self-generated spheroid models. Scaffolds generated using native matrix were most common (42%) with collagen I/hydroxyapatite predominating. Both scaffold-based and scaffold-free models were used equally for drug screening. The sensitivity of cancer cells in 3D was reported to be lower than that of cells in 2D in ~90% of the drug screening studies. This correlates with the observed upregulation of drug resistance. OS cells cultured in extracellular matrix (ECM)-mimetic scaffolds and native biomaterials were more resistant than cells in 2D. Co-cultures of OS and stromal cells in 3D models enhanced osteogenic differentiation, ECM remodelling, mineralisation, and angiogenesis, suggesting that tumour-stroma crosstalk promotes disease progression. Seven studies demonstrated selective toxicity of chemotherapeutics towards OS cells while sparing stromal cells, providing useful evidence for developing biomimetic tumour-stroma models to test selective drug toxicity. In conclusion, this review highlights the need to enhance biomimicry in 3D OS models for TME recapitulation, especially in testing novel therapeutics. Future research should explore innovative 3D biomimetic models, biomaterials, and advancements in personalised medicine.
摘要：
这项范围审查评估了3D骨肉瘤(OS)模型的仿生，检查它们模拟肿瘤微环境(TME)的能力和药物敏感性。坚持PRISMA-ScR准则，系统搜索揭示了293项研究，其中70人被选中进行最终分析。总的来说,64%的3DOS模型是基于支架的，与自生成球体模型相比。使用天然基质产生的支架是最常见的(42%),其中胶原I/羟基磷灰石占优势。基于支架的模型和无支架的模型同样用于药物筛选。据报道，在约90％的药物筛选研究中，3D中癌细胞的敏感性低于2D中细胞的敏感性。这与观察到的耐药性上调相关。在细胞外基质（ECM）模拟支架和天然生物材料中培养的OS细胞比2D中的细胞更具抵抗力。OS和基质细胞在3D模型中的共培养增强了成骨分化，ECM重塑，矿化，和血管生成，提示肿瘤-基质串扰促进疾病进展。七项研究表明，化疗药物对OS细胞的选择性毒性，同时保留基质细胞，为开发仿生肿瘤基质模型以测试选择性药物毒性提供有用的证据。总之,这篇综述强调了在TME重述的3DOS模型中增强仿生的必要性，特别是在测试新疗法方面。未来的研究应该探索创新的三维仿生模型，生物材料,以及个性化医疗的进步。
