文章：

三维骨肉瘤模型仿生学增强研究：范围综述

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

原文发布日期：28 December 2023

DOI: 10.3390/cancers16010164

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

本范围综述评估了三维骨肉瘤（OS）模型的生物仿生性，考察其模拟肿瘤微环境（TME）的能力及药物敏感性。遵循PRISMA-ScR指南，系统检索共纳入293项研究，最终筛选70项进行分析。总体而言，64%的三维骨肉瘤模型采用支架构建法，而自生成球体模型占比较低。使用天然基质制备的支架最为常见（42%），其中以I型胶原/羟基磷灰石为主。支架构建模型与无支架模型在药物筛选中应用比例相当。约90%的药物筛选研究表明，三维培养中癌细胞的药物敏感性低于二维培养，这与观察到的耐药性上调现象相符。在模拟细胞外基质（ECM）的支架及天然生物材料中培养的骨肉瘤细胞，较二维培养细胞表现出更强的耐药性。三维模型中骨肉瘤细胞与基质细胞的共培养体系可增强成骨分化、ECM重塑、矿化及血管生成，提示肿瘤-基质交互作用促进疾病进展。七项研究证实化疗药物对骨肉瘤细胞具有选择性毒性且不损伤基质细胞，为开发用于测试药物选择性毒性的仿生肿瘤-基质模型提供了重要依据。综上，本综述强调需提升三维骨肉瘤模型的生物仿生性以更好模拟肿瘤微环境，尤其在新型疗法测试领域。未来研究应聚焦创新三维仿生模型、生物材料开发及个体化医疗的进展。

原文链接：

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review