AIM 3D Cell Culture Chips offer a new perspective in studying angiogenesis by allowing the growth of new vascular sprouts in a 3D matrix from a pre-existing endothelial monolayer. With the transparent laminate at the bottom, the dynamic process of angiogenesis can be monitored in detail from a viewing angle that is perpendicular to the direction of sprouting. The two-media- channel design not only enables the generation of concentration gradient of angiogenic stimuli but also the application of interstitial flow that is very useful in inducing angiogenesis. This protocol covers the techniques to obtain consistent angiogenic sprouting in AIM chips.   


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  1. Design, fabrication and implementation of a novel multi-parameter control microfluidic platform for three-dimensional cell culture and real-time imaging. Vickerman V, Blundo J, Chung S, Kamm R. Lab Chip, 2008. 8 (9):1468-1477
  2. Surface-Treatment-Induced Three-Dimensional Capillary Morphogenesis in a Microfluidic Platform. Chung S, Sudo R, Zervantonakis IK, Rimchala T, Kamm RD. Advanced Materials, 2009. 21 (47):4863-4867
  3. Transport-mediated angiogenesis in 3D epithelial coculture. Sudo R, Chung S, Zervantonakis IK, Vickerman V, Toshimitsu Y, Griffith LG, Kamm RD. FASEB J., 2009. 23 (7):2155-2164
  4. Determining Cell Fate Transition Probabilities to VEGF/Ang 1 Levels: Relating Computational Modeling to Microfluidic Angiogenesis Studies. Das A, Lauffenburger D, Asada H, Kamm R. Cellular and Molecular Bioengineering, 2010. 3 (4):345-360
  5. Sprouting angiogenesis under a chemical gradient regulated by interactions with an endothelial monolayer in a microfluidic platform. Jeong GS, Han S, Shin Y, Kwon GH, Kamm RD, Lee SH, Chung S. Analytical Chemistry, 2011. 83 (22):8454-8459
  6. In vitro 3D collective sprouting angiogenesis under orchestrated ANG-1 and VEGF gradients. Shin Y, Jeon JS, Han S, Jung GS, Shin S, Lee SH, . . . Chung S. Lab Chip, 2011. 11 (13):2175-2181
  7. Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures. Farahat WA, Wood LB, Zervantonakis IK, Schor A, Ong S, Neal D, . . . Asada HH. PLoS ONE, 2012. 7 (5):e37333
  8. Engineering of In Vitro 3D Capillary Beds by Self-Directed Angiogenic Sprouting. Chan JM, Zervantonakis IK, Rimchala T, Polacheck WJ, Whisler J, Kamm RD. PLoS ONE, 2012. 7 (12):e50582
  9. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels. Shin Y, Han S, Jeon JS, Yamamoto K, Zervantonakis IK, Sudo R, . . . Chung S. Nature Protocols, 2012. 7 (7):1247-1259
  10. In vitro angiogenesis assay for the study of cell-encapsulation therapy. Kim C, Chung S, Yuchun L, Kim M-C, Chan JKY, Asada HH, Kamm RD. Lab Chip, 2012. 12 (16):2942-2950
  11. Complementary effects of ciclopirox olamine, a prolyl hydroxylase inhibitor and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting. Lim SH, Kim C, Aref AR, Kamm RD, Raghunath M. Integr. Biol., 2013. 5 (12):1474-1484
  12. *Crumbs proteins regulate layered retinal vascular development required for visionSon S,  Cho M and Lee J.  Biochemical and Biophysical Research Communications, Volume 521, Issue 422 January 2020, Pages 939-946.

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