CellWell: A micropatterned biphasic nanocomposite platform for culturing chondrocytes

Graphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC=\"FIGDIR/small/790030v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@e0a6c0org.highwire.dtl.DTLVardef@e3b9f7org.highwire.dtl.DTLVardef@c60cb6org.highwire.dtl.DTLVardef@6cb884_HPS_FORMAT_FIGEXP M_FIG C_FIG AbstractWe present a unique micropatterned nanocomposite cell culture platform to model articular cartilage that is suitable for high-throughput single-cell analyses using standard imaging techniques. This platform, the CellWell, is constructed out of a thin, optically transparent substrate that is lithographically micropatterned with a network of wells sized to fit individual cells. The substrate material consists of a thin layer of agarose hydrogel embedded with polyvinyl alcohol nanofibers. The geometries of the wells are designed to reinforce a physiological morphology, thereby combining the physiological advantages of 3D culture systems with the practical advantages of 2D systems. CellWells were found to have compressive moduli of 144 {+/-} 11.5 kPa and 158 {+/-} 0.6 kPa at strain rates of 5 m/s and 15 m/s. The compressive moduli were determined at two different strain rates to allow for comparison of CellWell stiffness with published values of pericellular matrix and with observed values of articular cartilage, which could not be indented at the same rate. Articular chondrocytes seeded in a CellWell were found to maintain their spheroidal morphology more effectively than those seeded in monolayer cultures and to be more easily imaged than those seeded in a 3D scaffold of identical thickness. Through its ease of use and ability to maintain the physiological morphology of chondrocytes, we expect that the CellWell will enhance the clinical translatability of future studies conducted using this culture platform.