Gastrointestinal tract (GIT) malignancies are an important public health problem considering the increased incidence in recent years and the high morbidity and mortality associated with it. GIT malignancies constitute 26% of the global cancer incidence burden and 35% of all cancer-related deaths. Gastrointestinal cancers are complex and heterogenous diseases caused by the interplay of genetic and environmental factors. The tumor microenvironment (TME) of gastrointestinal tract carcinomas is dynamic and complex; it cannot be recapitulated in the basic two-dimensional cell culture systems. In contrast, three-dimensional (3D) in vitro models can mimic the TME more closely, enabling an improved understanding of the microenvironmental cues involved in the various stages of cancer initiation, progression, and metastasis. However, the heterogeneity of the TME is incompletely reproduced in these 3D culture models, as they fail to regulate the orientation and interaction of various cell types in a complex architecture. To emulate the TME, 3D bioprinting has emerged as a useful technique to engineer cancer tissue models. Bioprinted cancer tissue models can potentially recapitulate cancer pathology and increase drug resistance in an organ-mimicking 3D environment. In this review, we describe the 3D bioprinting methods, bioinks, characterization of 3D bioprinted constructs, and their application in developing gastrointestinal tumor models that integrate their microenvironment with different cell types and substrates, as well as bioprinting modalities and their application in therapy and drug screening. We review prominent studies on the 3D bioprinted esophageal, hepatobiliary, and colorectal cancer models. In addition, this review provides a comprehensive understanding of the cancer microenvironment in printed tumor models, highlights current challenges with respect to their clinical translation, and summarizes future perspectives.

中文翻译：

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胃肠道癌症模型的 3D 生物打印：对加工、特性和治疗意义的全面回顾。

考虑到近年来发病率增加以及与之相关的高发病率和死亡率，胃肠道 (GIT) 恶性肿瘤是一个重要的公共卫生问题。GIT 恶性肿瘤占全球癌症发病率的 26%，占所有癌症相关死亡的 35%。胃肠道癌症是由遗传和环境因素相互作用引起的复杂和异质性疾病。胃肠道癌的肿瘤微环境 (TME) 是动态且复杂的；它不能在基本的二维细胞培养系统中概括。相比之下，三维 (3D) 体外模型可以更紧密地模拟 TME，从而更好地理解癌症发生、进展和转移各个阶段所涉及的微环境线索。然而，TME 的异质性在这些 3D 培养模型中没有完全再现，因为它们无法调节复杂结构中各种细胞类型的方向和相互作用。为了模拟 TME，3D 生物打印已成为一种有用的技术来设计癌症组织模型。生物打印的癌症组织模型有可能重现癌症病理学并在模拟器官的 3D 环境中增加耐药性。在这篇综述中，我们描述了 3D 生物打印方法、生物墨水、3D 生物打印结构的表征，以及它们在开发将微环境与不同细胞类型和基质相结合的胃肠道肿瘤模型中的应用，以及生物打印方式及其在治疗和药物中的应用筛选。我们回顾了关于 3D 生物打印食管、肝胆、和结直肠癌模型。此外，这篇综述提供了对印刷肿瘤模型中癌症微环境的全面了解，强调了当前在临床转化方面面临的挑战，并总结了未来的前景。