Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture.
Multicellular spheroids are an important 3-dimensional cell culture model that reflects many key aspects of in vivo microenvironments. This paper presents a scalable, self-assembly based approach for fabricating microcavity substrates for multicellular spheroid cell culture. Hydrophobic glass microbeads were self-assembled into a tightly packed monolayer through the combined actions of surface tension, gravity, and lateral capillary forces at the water-air interface of a polymer solution. The packed bead monolayer was subsequently embedded in the dried polymer layer. The surface was used as a template for replicating microcavity substrates with perfect spherical shapes. We demonstrated the use of the substrate in monitoring the formation process of tumor spheroids, a proof-of-concept scale-up fabrication procedure into standard microplate formats, and its application in testing cancer drug responses in the context of bone marrow stromal cells. The presented technique offers a simple and effective way of forming high-density uniformly-sized spheroids without microfabrication equipment for biological and drug screening applications.
Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, MA, 02114, USA.
Keyue
K
Shen
Jungwoo
J
Lee
Martin L
ML
Yarmush
Biju
B
Parekkadan
D001943:Breast Neoplasms; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D055616:Microtechnology; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism; D013499:Surface Properties
D011108:Polymers