Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low-Concentration Collagen-Based Bioinks.
Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low-Concentration Collagen-Based Bioinks.
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使用低浓度胶原蛋白生物墨水对乳腺肿瘤细胞和类器官进行嵌入式生物打印。
DOI：
10.1002/adhm.202300905
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发表时间：
2023
影响因子：
10
通讯作者：
Duan,Bin
中科院分区：
文献类型：
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作者：
Shi,Wen;Mirza,Sameer;Kuss,Mitchell;Liu,Bo;Hartin,Andrew;Wan,Shibiao;Kong,Yunfan;Mohapatra,Bhopal;Krishnan,Mena;Band,Hamid;Band,Vimla;Duan,Bin
用于肿瘤模型3D生物打印的生物墨水不仅应满足可打印性要求，还应准确维持和支持肿瘤周围细胞的表型，以重现关键的肿瘤标志。胶原蛋白是实体瘤的主要细胞外基质蛋白，但胶原蛋白溶液的低粘度使得3D生物打印癌症模型具有挑战性。这项工作使用低浓度基于I型胶原蛋白的生物墨水生产了包埋的、生物打印的乳腺癌细胞和肿瘤类器官模型。生物相容性和物理交联的丝素蛋白水凝胶用于生成用于嵌入式3D打印的支撑浴。基于I型胶原蛋白的生物墨水的组成通过基于热响应性透明质酸的聚合物进行优化，以保持非侵袭性上皮和侵袭性乳腺癌细胞以及癌症相关成纤维细胞的表型。使用优化的胶原生物墨水生物打印小鼠乳腺肿瘤类器官以模拟体内肿瘤形态。还使用类似的策略创建血管化肿瘤模型，在缺氧下显著增强血管形成。这项研究表明，利用低浓度胶原蛋白生物墨水的嵌入式生物打印乳腺肿瘤模型具有巨大潜力，可以促进对肿瘤细胞生物学的理解并促进药物发现研究。
Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low‐concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized with a thermoresponsive hyaluronic acid‐based polymer to maintain the phenotypes of both the noninvasive epithelial and invasive breast cancer cells, as well as cancer‐associated fibroblasts. Mouse breast tumor organoids are bioprinted using optimized collagen bioink to mimic in vivo tumor morphology. A vascularized tumor model is also created using a similar strategy, with significantly enhanced vasculature formation under hypoxia. This study shows the great potential of embedded bioprinted breast tumor models utilizing a low‐concentration collagen‐based bioink for advancing the understanding of tumor cell biology and facilitating drug discovery research.