The tumor extracellular matrix (ECM) plays a vital role in tumor progression and drug resistance. Previous studies have shown that breast tissue-derived matrices could be an important biomaterial to recreate the complexity of the tumor ECM. We have developed a method for decellularizing and delipidating a porcine breast tissue (TDM) compatible with hydrogel formation. The addition of gelatin methacrylamide and alginate allows this TDM to be bioprinted by itself with good printability, shape fidelity, and cytocompatibility. Furthermore, this bioink has been tuned to more closely recreate the breast tumor by incorporating collagen type I (Col1). Breast cancer cells (BCCs) proliferate in both TDM bioinks forming cell clusters and spheroids. The addition of Col1 improves the printability of the bioink as well as increases BCC proliferation and reduces doxorubicin sensitivity due to a downregulation of HSP90. TDM bioinks also allow a precise three-dimensional printing of scaffolds containing BCCs and stromal cells and could be used to fabricate artificial tumors. Taken together, we have proven that these novel bioinks are good candidates for biofabricating breast cancer models.

中文翻译：

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生物打印脱细胞乳腺组织用于开发三维乳腺癌模型

肿瘤细胞外基质（ECM）在肿瘤进展和耐药性中起着至关重要的作用。先前的研究表明，乳腺组织衍生的基质可能是重建肿瘤 ECM 复杂性的重要生物材料。我们开发了一种与水凝胶形成相容的猪乳房组织 (TDM) 脱细胞和脱脂的方法。明胶甲基丙烯酰胺和海藻酸盐的添加使这种 TDM 能够自行进行生物打印，具有良好的可印刷性、形状保真度和细胞相容性。此外，这种生物墨水已被调整为通过结合 I 型胶原蛋白 (Col1) 更紧密地重建乳腺肿瘤。乳腺癌细胞 (BCC) 在 TDM 生物墨水中增殖，形成细胞簇和球体。由于 HSP90 的下调，Col1 的添加提高了生物墨水的可印刷性并增加了 BCC 增殖并降低了阿霉素的敏感性。TDM 生物墨水还允许对含有 BCC 和基质细胞的支架进行精确的 3D 打印，并可用于制造人造肿瘤。总之，我们已经证明这些新型生物墨水是生物制造乳腺癌模型的良好候选者。