Combinatorial Development of Biomaterials for Stem Cell Engineering

Human pluripotent stem cells hold enormous potential for applications in regenerative medicine and human disease modeling. They have the unique ability to undergo self-renewal indefinitely in culture and have potential to differentiate into almost all cell types in human body. Such cells can either be derived from human embryos or be ‘reprogrammed' from patient's blood, skin, and fat samples. However, current methods to clonally grow them are inefficient and poorly-defined for genetic manipulation and therapeutic purposes. Here I report combinatorial development of synthetic biomaterials that support robust self-renewal of fully dissociated human pluripotent stem cells, preserve a normal karyotype, and maintain full differentiation capacity after prolonged cell culture. To the best of our knowledge, these materials provide the first chemically defined, xeno-free, feeder-free system to support the efficient clonal growth of human pluripotent stem cells at unprecedented high levels. Materials properties including surface topography after protein adsorption, surface wettability, molecular surface chemistry and reduced indentation modulus of all polymeric substrates were quantified using high-throughput methods to develop structure/function relationships between materials properties and biological performance. The studies described here provide a global understanding of relationships between human pluripotent stem cell growth and synthetic materials, as well as a general framework for the development of synthetic surfaces for stem cell culture.