描绘骨转移性癌症研究的前进道路:3D工程模型和生物打印支架在重现骨肿瘤微环境中的应用

Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone-Tumor Niche.

作者信息

Hughes Anne M, Kolb Alexus D, Shupp Alison B, Shine Kristy M, Bussard Karen M

机构信息

Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USA.

Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

Cancers (Basel). 2021 Jan 29;13(3):507. doi: 10.3390/cancers13030507.

Abstract

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone-tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone-tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles.

摘要

乳腺癌通常会转移至骨骼,导致溶骨性病变,并使患者生活质量下降。骨细胞外基质(ECM)通过提供支持细胞间相互作用的物理和生化线索,在癌细胞转移中发挥关键作用。当前的二维体外模型缺乏天然ECM的空间和生化复杂性,无法完全重现肿瘤与内源性基质细胞之间发生的相互作用。诸如芯片上的骨、骨髓外骨和生物反应器等工程模型目前用于模拟细胞间相互作用和骨肿瘤细胞相互作用,但仍无法提供仿生骨微环境。三维生物打印允许将生物相容性材料和活细胞沉积在复杂结构中,还提供了一种在体外更好地复制生物组织微环境的方法。特别是在癌症研究中,3D构建体在模拟癌细胞向骨骼扩散以及骨骼中骨肿瘤细胞相互作用的开创性工作中发挥了重要作用。此外,使用生物相容性材料,如羟基磷灰石,能够打印出具有植入体内动物模型并进行研究能力的类骨微环境。而且,生物打印模型的使用可能推动新型癌症治疗方法和药物递送载体的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d83/7865550/b86941273753/cancers-13-00507-g001.jpg

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