Abstract：
Bone metastasis primarily occurs when breast, prostate, or lung cancers disseminate tumoral cells into bone tissue, leading to a range of complications in skeletal tissues and, in severe cases, paralysis resulting from spinal cord compression. Unfortunately, our understanding of pathophysiological mechanisms is incomplete and the translation of bone metastasis research into the clinic has been slow, mainly due to the lack of credible ex vivo and in vivo models to study the disease progression. Development of reliable and rational models to study how tumor cells become circulating cells and then invade and sequentially colonize the bone are in great need. Advances in tissue engineering technologies offers reliable 3D tissue alternatives which answer relevant research questions towards the understanding of cancer evolution and key functional properties of metastasis progression as well as prognosis of therapeutic approach. Here we performed an overview of cellular mechanisms involved in bone metastasis including a short summary of normal bone physiology and metastasis initiation and progression. Also, we comprehensively summarized current advances and methodologies in fabrication of reliable bone tumor models based on state-of-the-art printing technologies which recapitulate structural and biological features of native tissue. STATEMENT OF SIGNIFICANCE: This review provides a comprehensive summary of the collective findings in relation to various printed bone metastasis models utilized for investigating specific bone metastasis diseases, related characteristic functions and chemotherapeutic drug screening. These tumoral models are comprehensively evaluated and compared, in terms of their ability to recapitulate physiological metastasis microenvironment. Various biomaterials (natural and synthetic polymers and ceramic based substrates) and printing strategies and design architecture of models used for printing of 3D bone metastasis models are discussed here. This review clearly out-lines current challenges and prospects for 3D printing technologies in bone metastasis research by focusing on the required perspective models for clinical application of these technologies in chemotherapeutic drug screening.
摘要：
骨转移主要发生在乳腺，前列腺,或肺癌将肿瘤细胞传播到骨组织中，导致一系列骨骼组织并发症，在严重的情况下，脊髓压迫导致的瘫痪。不幸的是,我们对病理生理机制的理解不完整，骨转移研究进入临床的过程缓慢，主要是由于缺乏可靠的离体和体内模型来研究疾病进展。非常需要开发可靠和合理的模型来研究肿瘤细胞如何成为循环细胞，然后侵入并依次定植于骨骼。组织工程技术的进步提供了可靠的3D组织替代方案，这些方案回答了相关的研究问题，以了解癌症的演变和转移进展的关键功能特性以及治疗方法的预后。在这里，我们对涉及骨转移的细胞机制进行了概述，包括对正常骨生理学以及转移开始和进展的简短总结。此外，我们全面总结了基于最先进的印刷技术制造可靠骨肿瘤模型的最新进展和方法，这些技术概括了天然组织的结构和生物学特征。重要声明：这篇综述提供了与用于研究特定骨转移疾病的各种印刷骨转移模型相关的集体发现的全面总结。相关特征功能及化疗药物筛选。对这些肿瘤模型进行综合评价和比较,就其重现生理转移微环境的能力而言。本文讨论了各种生物材料（天然和合成聚合物以及基于陶瓷的基材）以及用于3D骨转移模型打印的模型的打印策略和设计体系结构。这篇综述通过关注这些技术在化疗药物筛选中的临床应用所需的视角模型，清楚地揭示了3D打印技术在骨转移研究中的当前挑战和前景。
