The overarching goals of this proposal are to; one, research and develop transparent ultrathin nanomembranes and two, utilize these membranes to advance biomedical in vitro model systems through work in the laboratory of the PI and an array of current and future collaborators. Nanomembrane development will include research towards fabricating ultrathin nanoporous silicon dioxide membranes, scaling up their active area, creating unique surface chemistries to promote cellular interaction and integration of sensor technologies. This proposal will enable collaborators to visualize endothelial barrier transmigration, produce better in vitro corneal models and visualize motile cilia in a patient derived primary lung model of cystic fibrosis. In addition, nanomembrane development through this proposal will enable and supply new collaborators with the tools to solve existing challenges and expand their respective fields. A common need is the ability to culture cells in a physiologically relevant model system that can be visualized in real-time. Transparent ultrathin porous membranes can accomplish this for almost any barrier model and co-culture system. SiO2 nanomembranes enable co-cultured cells to be brought within physiological separations distances (~100 nm), while providing glass-like optical transparency and nearly unhindered transport of signaling molecules. Success in developing new human in vitro systems promises to reduce the reliance on animal models, while simultaneously increasing physiological relevance and accelerating drug development. These tissue- and organ-on-a-chips also make feasible live imaging of complex cellular events that require sophisticated and well-orchestrated microenvironments.
The overall aim of this research proposal is to develop optically transparent nanomembranes to enable improved in vitro tissue models. These models will aid in drug candidate screening as well as improve our understanding of cellular interactions during tissue development.
| Chung, Henry H; Mireles, Marcela; Kwarta, Bradley J et al. (2018) Use of porous membranes in tissue barrier and co-culture models. Lab Chip 18:1671-1689 |
| Chung, Henry H; Casillo, Stephanie M; Perry, Spencer J et al. (2018) Porous Substrates Promote Endothelial Migration at the Expense of Fibronectin Fibrillogenesis. ACS Biomater Sci Eng 4:222-230 |
| Chung, Henry H; Bellefeuille, Sean D; Miller, Hayley N et al. (2018) Extended live-tracking and quantitative characterization of wound healing and cell migration with SiR-Hoechst. Exp Cell Res 373:198-210 |
| Casillo, Stephanie M; Peredo, Ana P; Perry, Spencer J et al. (2017) Membrane Pore Spacing Can Modulate Endothelial Cell-Substrate and Cell-Cell Interactions. ACS Biomater Sci Eng 3:243-248 |
| Mireles, Marcela; Gaborski, Thomas R (2017) Fabrication techniques enabling ultrathin nanostructured membranes for separations. Electrophoresis 38:2374-2388 |
| Carter, Robert N; Casillo, Stephanie M; Mazzocchi, Andrea R et al. (2017) Ultrathin transparent membranes for cellular barrier and co-culture models. Biofabrication 9:015019 |
