Biomimetic Material

1. 3D Cell Culture for High-throughput Screening

3D cell culture platforms have been developed and applied to preclinical screening, which can mimic the physiological and diseased state in vivo while excluding the discrepancy between animals and humans. Most importantly, 3D cell culture as an in vitro platform allows high-throughput and high-content assays that can be integrated with imaging, automation, and computational tools to achieve preclinical drug screening for effective and precise drug discovery and drug development in pharmaceutical science and industry. 

The Wang Lab design and engineer 3D biomimetic scaffold with inverted colloidal crystal geometry to afford a high yield production of controlled size spheroids in standard 96-384 well-plates. Transparent hydrogel matrix and ship-in-bottle effect also allows for convenient monitoring of cell processes by convectional analytical techniques in real-time. We anticipate the presented system together with smart analytical tools and machine learning assisted algorithms will contribute to the development of various physiological and pathophysiological 3D tissue models which can be served as a valuable tool for understanding tissue level biology and in vitro drug testing application.

• Wang, Y.^* and Jeon, H. Three-Dimensional Cell Cultures toward Quantitative High-Throughput Cancer Drug Screening. Trends in Pharmacological Sciences 2022, 43, 11-24.
• Wang, Y.^*; Bahng, J. H.; Kotov, N. A. Three-Dimensional Biomimetic Scaffolds for Hepatic Differentiation of Size-Controlled Embryoid Bodies. J. Mater. Res. 2019, 34, 1371-1380.
• Wang, Y.^*; Jan, E.; Cuddihy, M.; Bahng, J. H.; Kotov, N. Layered Biomimetic Nanocomposites Replicate Bone Surface in Three-Dimensional Cell Cultures. Nanocomposites 2018, 4, 156–166.
• Wang, Y.; Bahng, J. H.; Che, Q.; Han, J.; Kotov, N. A. Anomalously Fast Diffusion of Targeted Carbon Nanotubes in Cellular Spheroids. ACS Nano 2015, 9, 8231–8238.

2. 3D Cell Culture for Extracellular Vesicle Manufacturing

Taking advantage of modern biomaterials and tools, 3D cell culture models were enabled to exhibit features mimicking in-vivo conditions which include cell morphology, physiology, cell-cell interactions, and cell-matrix interactions. Extracellular vesicles (EVs) derived from 3D cell cultures possess distinctive properties and functions influenced by their parent cell lines, culture geometries, and environmental factors. 3D cell culture systems improve the relative EV yield compared to 2D cell culture systems by an average of ~30 fold and ~3 fold, respectively. 3D cultured EVs also possess enhanced therapeutic properties that can be applied to tissue regeneration, drug-delivery based therapeutics, and immunomodulation therapies.

The Wang Lab designs and fabricate nanofibrous scaffolds with unique properties that can improve the quantity and quantity of EV production from 3D cell cultures with scalable potentials for large scale biomanufacturing. By implementing the nanofibrous scaffold into a perfusion reactor system, we will provide an avenue for large scale EV production with controlled quantity and quantity for various medical uses.

• Wang, Y.^*; Jan, E.; Cuddihy, M.; Bahng, J. H.; Kotov, N. Layered Biomimetic Nanocomposites Replicate Bone Surface in Three-Dimensional Cell Cultures. Nanocomposites 2018, 4, 156–166.
• Feng, Z.; Chu, X.; Huang, N.; Leach, M.; Wang, G.; Wang, Y.; Ding, Y.; Gu, Z. Rat Hepatocyte Aggregate Formation on Discrete Aligned Nanofibers of Type-I Collagen-Coated Poly(l-Lactic Acid). Biomaterials 2010, 31, 3604–3612.
• Feng, Z.; Leach, M.; Chu, X.; Wang, Y.; Tian, T.; Shi, X.; Ding, Y.; Gu, Z. Electrospun Chitosan Nanofibers for Hepatocyte Culture. J. Biomed. Nanotechnol. 2010, 6, 658–666.
• Feng, Z.; Chu, X.; Huang, N.; Wang, T.; Wang, Y.; Shi, X.; Ding, Y.; Gu, Z. The Effect of Nanofibrous Galactosylated Chitosan Scaffolds on the Formation of Rat Primary Hepatocyte Aggregates and the Maintenance of Liver Function. Biomaterials 2009, 30, 2753–2763.