A 3D Bioprinted Pancreatic Cancer Model Using Collagen-Gelatin Methacrylamide-Alginate Bioinks to Mimic the Desmoplastic Microenvironment

利用胶原蛋白-明胶甲基丙烯酰胺-海藻酸盐生物墨水构建3D生物打印胰腺癌模型,以模拟促纤维增生微环境

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Abstract

Pancreatic ductal adenocarcinoma is one of the cancers with the least favorable survival prognosis worldwide. It is characterized by a high desmoplastic stroma rich in collagen I, which regulates pancreatic cancer cells' behavior. There is a critical need to develop desmoplastic 3D models for preclinical testing. In this study, bioinks that imitate the biochemical characteristics of pancreatic ductal adenocarcinoma were developed to observe the influence that the desmoplastic extracellular matrix has on cancer cells. The bioinks were made of gelatin methacrylamide, alginate, and different concentrations of collagen I. Cancer cells were able to proliferate in all bioinks, presenting high paclitaxel resistance and a high expression of desmoplasia and extracellular matrix remodeling markers. The designed bioinks can play a crucial role in developing more clinically relevant cancer models for chemotherapeutic drug screening. Furthermore, they have significant potential for studying the influence of desmoplasia and for improving advanced treatment approaches for pancreatic cancer.

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