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癌症致命的主要原因是癌细胞在临床上的转移性. 癌细胞的侵袭和转移是一个非常复杂的三维过程, 但现有的癌症研究在活体上有诸多观测和操作上的困难. 而体外实验又通常在培养皿中进行, 其二维的生长环境已完全不能满足对癌细胞空间转移性的深入研究, 故在活体外构建出癌细胞侵袭和转移的三维物理模型具有十分重要的意义. 然而如何在体外尽可能真实地模拟体内癌细胞的生长微环境一直是困扰科学家的难题. 本文系统介绍了三维微纳米制造的几种主流技术, 探讨了它们在癌症生物物理研究中的应用和发展. 在此基础上为了在未来实现对体外三维模型的制造、观测和精确操作, 文章还创新性地提出了一种结合紫外线固化生物型水凝胶的三维成型技术、光片三维成像技术以及微纳米探针控制技术的一体化研究平台. 这些先进的技术和理念, 势必会逐步升级现有传统的癌症研究手段, 为未来理解和治疗癌症揭开全新的篇章.The major reason why cancer kills is its metastatic potentials. Metastasis is an extremely complex three-dimensional (3D) process. Currently, routine in vivo cancer research still experiences bottlenecks in observation and manipulation, while in vitro research mainly stays in petri-dish levels that limit cell environment with two-dimensional confinements. Therefore, it is in urgent needs to construct 3D in vitro models to deepen the studies in cancer invasion and metastasis. However “how to carry out” is a big question that harasses scientists for decades. In this report, we will systematically discuss several popular technologies for 3D microfabrication and their applications in bio and cancer research. Besides, we will demonstrate our efforts to construct an all-in-one 3D micro ecology simulation system (3D MESS) which highly integrates a UV bio-compatible hydrogel printer, a light-sheet imaging system, and a nano pipette operation system. This novel system will create a brand-new method to fabricate, observe and controls the 3D structures and the cells inside. We believe that these advanced technology and ambitions will definitely update the current cancer research methods and bring promising hopes for future deeper understandings and more efficient treatment of cancer.
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Keywords:
- three-dimensional micro/nano fabrication /
- cancer /
- cancer biophysics /
- in vivo microenvironment
[1] Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M J 2009 Ca-Cancer J. Clin. 59 225
[2] Wolgemuth C W 2011 Physics 4
[3] Tay C Y, Irvine S A, Boey F Y C, Tan L P, Venkatraman S 2011 Small 7 1361
[4] Pranav Soman, Jonathan Kelber A, Jin Woo Lee 2012 Biomaterials 33 7064
[5] Lu Y, Mapili G, Suhali G, Chen S, Roy K, J. A 2006 Biomed. Mater. Res. 77A 396
[6] Wang S, Foo C W P, Warrier A, Poo M M, Heilshorn S C, Zhang X 2009 Biomed. Microdvices. 11 1127
[7] Hoffman-Kim D, Mitchel J A, Bellamkonda R V 2010 Annu. Rev. Biomed. Eng. 12 203
[8] Zhang A P, Qu X, Soman P 2012 Adv. Mater. 24 4266
[9] Germán Comina, Anke Suskaa, Daniel Filippini 2014 Lab. Chip 14 424
[10] Kuo C T, Kuo C T, Chiang C L, Chang C H, Liu H K, Huang G S, Ruby Yun-Ju Huang, Leec H, Huang C S, Wo A M 2014 Biomaterials 35 1562
[11] Tiemo Bckmann, Nicolas Stenger 2012 Advanced Materials 24 2710
[12] Nelson B J, Kaliakatsos I K, Abbott J J, Annu 2010 Rev. Biomed. Eng. 12 55
[13] Klein F, Striebel T, Fischer J, Jiang Z, Franz C M, Freymann G, Wegener M, Bastmeyer M 2010 Adv. Mater. 22 868
[14] Sangwon Kim, Famin Qiu 2013 Adv. Mater. 25 5863
[15] Ying Zhang, Junmei Chen 2012 PNAS 109 24
[16] Connell J L, Ritschdorff E T 2013 PNAS 110 46
[17] Anselme K, Bigerelle M 2011 Int. Mater. Rev. 56 243
[18] Tina Qing Huang, Qu X, Justin Liu, Shaochen Chen 2014 Biomed Microdevices 16 127
[19] Kolin Hribar C, Pranav Soman, John Warner 2014 Lab. Chip 14 268
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[1] Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M J 2009 Ca-Cancer J. Clin. 59 225
[2] Wolgemuth C W 2011 Physics 4
[3] Tay C Y, Irvine S A, Boey F Y C, Tan L P, Venkatraman S 2011 Small 7 1361
[4] Pranav Soman, Jonathan Kelber A, Jin Woo Lee 2012 Biomaterials 33 7064
[5] Lu Y, Mapili G, Suhali G, Chen S, Roy K, J. A 2006 Biomed. Mater. Res. 77A 396
[6] Wang S, Foo C W P, Warrier A, Poo M M, Heilshorn S C, Zhang X 2009 Biomed. Microdvices. 11 1127
[7] Hoffman-Kim D, Mitchel J A, Bellamkonda R V 2010 Annu. Rev. Biomed. Eng. 12 203
[8] Zhang A P, Qu X, Soman P 2012 Adv. Mater. 24 4266
[9] Germán Comina, Anke Suskaa, Daniel Filippini 2014 Lab. Chip 14 424
[10] Kuo C T, Kuo C T, Chiang C L, Chang C H, Liu H K, Huang G S, Ruby Yun-Ju Huang, Leec H, Huang C S, Wo A M 2014 Biomaterials 35 1562
[11] Tiemo Bckmann, Nicolas Stenger 2012 Advanced Materials 24 2710
[12] Nelson B J, Kaliakatsos I K, Abbott J J, Annu 2010 Rev. Biomed. Eng. 12 55
[13] Klein F, Striebel T, Fischer J, Jiang Z, Franz C M, Freymann G, Wegener M, Bastmeyer M 2010 Adv. Mater. 22 868
[14] Sangwon Kim, Famin Qiu 2013 Adv. Mater. 25 5863
[15] Ying Zhang, Junmei Chen 2012 PNAS 109 24
[16] Connell J L, Ritschdorff E T 2013 PNAS 110 46
[17] Anselme K, Bigerelle M 2011 Int. Mater. Rev. 56 243
[18] Tina Qing Huang, Qu X, Justin Liu, Shaochen Chen 2014 Biomed Microdevices 16 127
[19] Kolin Hribar C, Pranav Soman, John Warner 2014 Lab. Chip 14 268
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