Chemically defined, plant-derived biomaterial platform for human cell culture

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NON-TECHNICAL SUMMARYStem cells are cells within our bodies that unlike most cells, have the potential to differentiate into many different types of cells. Stem cells have been an area of focused study in basic sciences due to their therapeutic potential in treating human disease. However, precise control over stem cell differentiation into useful therapeutic cells remains challenging, and better regulation of stem cell behaviors such as adhesion, proliferation, differentiation, and tissue formation could expedite biomedical applications of human stem cells. Natural and synthetic biomaterials can serve as a “scaffold” that controls the cell’s environment, often by mimicking the native environment in which the cells grow. Plants have developed unique and diverse material properties over more than 700 million years of evolution, and plant properties are ideally suited to support stem cell growth. The scalable, sustainable nature of plant leaf production, along with enhanced oxygen diffusion, wide diversity of morphology and length scales, and their biocompatibility, all make a strong case for their development as a broadly useful biomaterial for human stem cell manufacturing. However, plant-derived materials provide no intrinsic mechanism for proper attachment and function of human cells. The synthetic polymer coatings developed through this work will control cell-biomaterial attachment and present signals to stem cells that control their fate. The plant-derived biomaterials developed through this work can be delivered to cell biologists and bioengineers, who can use them to probe key biological questions or manufacture specific cells of interest. This research program will serve to educate and inspire rural high school students and teachers by the development of an interdisciplinary learning module. The award will enhance, retain, and promote engagement with underrepresented groups, through the Women in Science & Engineering Leadership Institute, and research experience for undergraduates at UW-Madison. TECHNICAL SUMMARYBiomaterials based on decellularized plant materials provide intricate interconnected vasculature for transport of biomolecules, as well as wide diversity in morphology and length scales for cell alignment and pattern registration. The research proposed here aims to develop a decellularized plant leaf-based biomaterial as a broadly useful and adaptable biomaterial for human cell culture. The research will test the hypothesis that plant-derived materials conformally coated with chemically-defined polymer films will support cell adhesion, viability and alignment, and also enhance stem cell differentiation toward functional tenocytes and myocytes. The work focuses on developing methodology to fully characterize plant-derived biomaterials and on developing coating chemistry to modify leaf surfaces to make them conducive for human cell culture. This understanding will allow systematic interrogation of the effect of surface topography and the customizable surface chemistry on the cellular alignment and differentiation. The expected outcomes of the proposed research are 1) the development of the decellularization process, and comprehensive characterization of chemical composition, cytotoxicity, morphology, enzymatic degradability, mass transport, and mechanical properties of the leaf material, 2) development of novel copolymer coating chemistry to minimize non-specific adsorption of biomolecules, enable the nanometer-scale co-localization of adhesion peptides, and quantitatively present a combination of muscle and tendon extra-cellular matrix derived peptides, and 3) correlating the leaf microtopography and surface chemistry with cell alignment during myogenic and tenogenic differentiation using second harmonic generation microscopy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.