The research objective of this Interdisciplinary Research (IDR) award is to collaboratively advance nanomanufacturing and biomedical science by exploring the development of human stem cells cultured on molded polymeric substrates with nanostructured surfaces. The successful differentiation and maturation of stem cells is critical to cell implantation therapeutics and tissue engineering. Since mammalian cells are significantly influenced by their physical environment, the incorporation of tailored nanostructured surfaces into tissue culture devices has great potential to enhance stem cell engineering by more effectively mimicking in vivo situations. The approach taken will be to utilize nanoscale injection molding to reliably and economically produce cell culture devices designed specifically for each cell phenotype of choice. Fully approved biocompatible polymers will be used, and molded surface features throughout the study will range from the sub-micron scale down to as small as 50 nanometers. Human mesenchymal stem cells will be studied initially, with other stem cell types included as the work evolves.
If successful, the benefits of this research will include the development of a practical and more effective route to optimally develop human stem cells for a wide range of medical applications. This would dramatically enhance the international position of U.S. based bioengineering firms active in this field. In addition, the fully coupled advancement of biomedical science with nanomanufacturing science will establish a new paradigm for approaching bioengineering challenges. This will benefit both the manufacturing community that needs to direct nanoscale manufacturing science advancements toward appropriate applications and the biomedical community that has so many important problems to solve. The research will also bolster the development of the future scientific workforce through the inclusion of a significant number of middle and high school students in the work each year. This will establish interdisciplinary scientific advancement as an enjoyable and productive norm in the minds of all involved.
Intellectual Merit: This award enabled the exploration of nano-scale injection molding as a way to tailor the surfaces of cell culture substrates to manipulate stem cell fate. This particular project was rooted in how injection-molding techniques could be used to produce devices that could enhance stem cell differentiation. In the early stages of the award, mechanotransduction of human mesenchymal stem cells (hMSCs) was studied. This is the process by which biophysical cues are sensed and interpreted by cells. These studies were carried out on standard tissue culture treated Petri dishes (made from polystyrene or glass). These products, while inexpensive and readily available, were found to produce undesirable effects on adherent cells through the process of mechanotransduction. Effects such as premature differentiation and/or aging phenomenon in cells were observed. Following these preliminary studies, manufacturing parameters to produce mechanically tunable cell culture substrates in the form of nano-structured materials were determined. These nano-structured materials, produced using injection molding techniques by the team, allowed for robust culture of stem cells (both human mesenchymal and other subtypes) in the absence of further chemical treatments, such as oxygen plasma, protein coatings, or other surface modifications. Through manufacturing, the team produced a suite of nano-structured surface features (thus altering the perceived flexural stiffness of the material) and found that the nano-structured surface allows for either long-term culture of stem cells (eliminating the aging effect) or controlled differentiation of the cells (into useful phenotypes for tissue engineering), depending upon material design. Broader Impacts: This award enabled the PI and Co-PI to develop and participate in several collaborative outreach programs, including NanoDays (with the DaVinci Center), CHOICES camp, Lehigh University Governor’s school, among others. In addition, multiple students were trained under the IDR award, including graduate students (3 in total, 2 female), undergraduates (15 in total, 7 female), and graduating high school students (1 in total). These students disseminated their results at a variety of conferences and through the preparation of various manuscripts, targeted at both the biomedical science community as well as the manufacturing community. Currently, the team is working on the next phase of the project, which involves translation of these nano-structured features to larger devices that can be used in place of standard tissue culture treated polystyrene devices in long-term cell culture. Partnerships with manufacturers of biomedical devices are being sought to license the injection molding technology. In addition, commercialization efforts are being pursued actively by the team.
