Schmid Rafael, Schmidt Sonja K, Schrüfer Stefan, Schubert Dirk W, Heltmann-Meyer Stefanie, Schicht Martin, Paulsen Friedrich, Horch Raymund E, Bosserhoff Anja K, Kengelbach-Weigand Annika, Arkudas Andreas
Laboratory for Tissue-Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Krankenhausstraße 12, 91054, Erlangen, Germany.
Institute of Biochemistry, Friedrich-Alexander University Erlangen-Nürnberg, Fahrstraße 17, 91054, Erlangen, Germany.
Mater Today Bio. 2024 Apr 27;26:101071. doi: 10.1016/j.mtbio.2024.101071. eCollection 2024 Jun.
Although 2D cancer models have been the standard for drug development, they don't resemble properties adequately. 3D models can potentially overcome this. Bioprinting is a promising technique for more refined models to investigate central processes in tumor development such as proliferation, dormancy or metastasis. We aimed to analyze bioinks, which could mimic these different tumor stages in a cast vascularized arteriovenous loop melanoma model . It has the advantage to be a closed system with a defined microenvironment, supplied only with one vessel-ideal for metastasis research. Tested bioinks showed significant differences in composition, printability, stiffness and microscopic pore structure, which led to different tumor stages (Matrigel and Alg/HA/Gel for progression, Cellink Bioink for dormancy) and resulted in different primary tumor growth (Matrigel significantly higher than Cellink Bioink). Light-sheet fluorescence microscopy revealed differences in vascularization and hemorrhages with no additional vessels found in Cellink Bioink. Histologically, typical human melanoma with different stages was demonstrated. HMB-45-positive tumors in progression inks were infiltrated by macrophages (CD163), highly proliferative (Ki67) and metastatic (MITF/BRN2, ATX, MMP3). Stainings of lymph nodes revealed metastases even without significant primary tumor growth in Cellink Bioink. This model can be used to study tumor pathology and metastasis of different tumor stages and therapies.
尽管二维癌症模型一直是药物研发的标准，但它们无法充分模拟肿瘤特性。三维模型有可能克服这一问题。生物打印是一种很有前景的技术，可用于构建更精细的模型，以研究肿瘤发展的核心过程，如增殖、休眠或转移。我们旨在分析生物墨水，其能够在一种铸型血管化动静脉环黑色素瘤模型中模拟这些不同的肿瘤阶段。该模型具有优势，它是一个具有明确微环境的封闭系统，仅通过一根血管供血——这对转移研究来说非常理想。测试的生物墨水在成分、可打印性、硬度和微观孔隙结构方面存在显著差异，这导致了不同的肿瘤阶段（基质胶和Alg/HA/Gel用于肿瘤进展，Cellink生物墨水用于休眠），并导致了不同的原发性肿瘤生长情况（基质胶显著高于Cellink生物墨水）。光片荧光显微镜检查揭示了血管生成和出血方面的差异，在Cellink生物墨水中未发现额外的血管。组织学检查显示了不同阶段的典型人类黑色素瘤。进展期墨水中HMB - 45阳性肿瘤被巨噬细胞（CD163）浸润，具有高增殖性（Ki67）和转移性（MITF/BRN2、ATX、MMP3）。淋巴结染色显示，即使在Cellink生物墨水中原发性肿瘤生长不显著的情况下也出现了转移。该模型可用于研究不同肿瘤阶段的肿瘤病理学和转移情况以及治疗方法。
