Department of Clinical Surgical Sciences; integrated unit of experimental surgery, advanced microsurgery and regenerative medicine, University of Pavia, Pavia, Italy.
Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
J Biomed Mater Res B Appl Biomater. 2023 Aug;111(8):1571-1580. doi: 10.1002/jbm.b.35255. Epub 2023 Apr 4.
Osteosarcoma is the most frequently primary malignant bone tumor characterized by infiltrative growth responsible for relapses and metastases. Treatment options are limited, and a new therapeutic option is required. Boron neutron capture therapy (BNCT) is an experimental alternative radiotherapy able to kill infiltrative tumor cells spearing surrounding healthy tissues. BNCT studies are performed on 2D in vitro models that are not able to reproduce pathological tumor tissue organization or on in vivo animal models that are expensive, time-consuming and must follow the 3R's principles. A 3D in vitro model is a solution to better recapitulate the complexity of solid tumors meanwhile limiting the animal's use. Objective of this study is to optimize the technical assessment for developing a 3D in vitro osteosarcoma model as a platform for BNCT studies: printing protocol, biomaterial selection, cell density, and crosslinking process. The best parameters that allow a fully colonized 3D bioprinted construct by rat osteosarcoma cell line UMR-106 are 6 × 10 cells/ml of hydrogel and 1% CaCl as a crosslinking agent. The proposed model could be an alternative or a parallel approach to 2D in vitro culture and in vivo animal models for BNCT experimental study.
骨肉瘤是最常见的原发性恶性骨肿瘤，其特征为浸润性生长，导致复发和转移。治疗选择有限，需要新的治疗方法。硼中子俘获治疗（BNCT）是一种实验性的放射治疗替代方法，能够杀死浸润性肿瘤细胞，同时保护周围的健康组织。BNCT 研究在 2D 体外模型上进行，这些模型无法复制病理性肿瘤组织的结构，或者在昂贵、耗时且必须遵循 3R 原则的动物模型上进行。3D 体外模型是更好地模拟实体瘤复杂性的解决方案，同时限制动物的使用。本研究的目的是优化开发 3D 体外骨肉瘤模型的技术评估，作为 BNCT 研究的平台：打印方案、生物材料选择、细胞密度和交联过程。允许大鼠骨肉瘤细胞系 UMR-106 完全定植的 3D 生物打印结构的最佳参数是 6×10 细胞/ml 的水凝胶和 1%CaCl2 作为交联剂。所提出的模型可以作为 BNCT 实验研究的 2D 体外培养和体内动物模型的替代或并行方法。
