Mechanical stiffness-defined matrices for stem cell research and drug screening

Synthetic polymer matrices or subtrata with tailored elastic properties provide a powerful method to direct biological cell' differentiation and foster cell multiplication. By changing the stiffness of the substrate, human mesenchymal stem cell (MSCs) could be directed along neuronal, muscle, or bone lineages. Matrix elastic modulus can also control anchorage dependent cell's motility, localization, tissue formation and organization. Besides that, synthetic materials such as biodegradable polymers offer a versatile alternative to naturally derived biopolymers. Their mechanical properties can be highly tailored and they are easy to synthesize and shape. Moreover, these platforms can be readily "biologically" fine-tuned toward a particular cell linage by incorporating well-documented parameters, which play crucial roles in cell-extra cellular matrix (ECM) signaling pathway, such as growth factor, surface topology and stimulation signal. Hence, these materials are suitable candidates to develop engineered matrices for stem cell culture, cell manipulating platforms in biological research and drug development. In this thesis, commercialization aspects of these engineered matrices for stem cell research, cell culture and drug development markets are evaluated both in USA and in Singapore markets. Technological barriers, intellectual property and a preliminary cost model are analyzed. A business plan is presented and discussed for applications in both the stem cell research and the drug screening markets. Although these two markets are ill-defined, both of them are growing rapidly and appear to be very promising. A review of the technology itself led to the conclusion that the matrix is capable of induce anchorage dependent cell into specific lineage but the success rate is not yet quantified and further research need to be done to achieve good reproducibility and to meet the required efficacy of the industry. Thesis Advisor: Krystyn J. Van Vliet Title: Thomas Lord Assistant Professor of Materials Science and Engineering Mechanical Stiffness-Defined Matrices for Stem Cell Research and Drug Screening Acknowledgments I would like to take this opportunity to express my heartfelt gratefulness to those who have assisted me in one way or another towards the completion of my thesis. Without their supervision, guidance, assistance, and support, the project would not have been to existence. First and foremost, I would like to thank my thesis advisor, Assistant Professor Krystyn J. Van Vliet, for her supervision, guidance and suggestions on the project. She has helped me filtering irrelevant information, provided valuable articles and advices for the thesis. She recommended many ways to improve the thesis's content and brought up to date about relevant researches. I am grateful to Assistant Professor Wang Dong An from Nanyang Technological University, Singapore, Professor Ramakrishna Seeram, Professor Teoh Swee-Hin, Professor Hanry Yu from National University of Singapore, Dr. Dean Tai from Institute of BioNanotechnology, Singapore and Dr. Thuan D. Bui from iDNA Pte. Ltd for their guidance, comment and advice for the thesis. With their patience, they have constantly inspired me to tackle numerous difficulties and to come up with creative ideas. Their knowledge, advice, review and support in finding out the methods and valuable information to carry on the analysis in this thesis are remarkably valuable. Their supports and professionalism are beyond the scope of the thesis. My thanks also go to my friends, Yuyan, Weimin and Thu Trang for their help on Cost Modeling. They have also shared their experiences in business planning and market analysis. Their reliable backings have made difficult tasks manageable. Finally, I wish to thank my Mom, my Dad, my brother and much-loved Thanh Hoai for their consistent support, and encouragement, making my studies at MIT a memorable one. Mechanical Stiffness-Defined Matrices for Stem Cell Research and Drug Screening