Bioinspired Materials for Controlling Stem Cell Fate

摘要

Although researchers currently have limited abil-nity to mimic the natural stem cell microenvi-nronment, recent work at the interface of stem biologynand biomaterials science has demonstrated that con-ntrol over stem cell behavior with artificial microen-nvironments is quite advanced. Embryonic and adultnstem cells are potentially useful platforms for tissuenregeneration, cell-based therapeutics, and disease-nin-a-dish models for drug screening. The major chal-nlenge in this field is to reliably control stem cellnbehavior outside the body. Common biological con-ntrol schemes often ignore physicochemical parame-nters that materials scientists and engineers commonlynmanipulate, such as substrate topography andnmechanical and rheological properties. However, with appropriate attention to these parameters, researchers have designed novelnsynthetic microenvironments to control stem cell behavior in rather unnatural ways.nIn this Account, we review synthetic microenvironments that aim to overcome the limitations of natural niches rather than to mimicnthem. A biomimetic stem cell control strategy is often limited by an incomplete understanding of the complex signaling pathways thatndrive stem cell behavior from early embryogenesis to late adulthood. The stem cell extracellular environment presents a miscellany ofncompeting biological signals that keep the cell in a state of unstable equilibrium. Using synthetic polymers, researchers have designednsynthetic microenvironments with an uncluttered array of cell signals, both specific and nonspecific, that are motivated by rather thannmodeled after biology. These have proven useful in maintaining cell potency, studying asymmetric cell division, and controlling cellularndifferentiation.nWe discuss recent research that highlights important biomaterials properties for controlling stem cell behavior, as well as advancednprocesses for selecting those materials, such as combinatorial and high-throughput screening. Much of this work has utilized micro- andnnanoscale fabrication tools for controlling material properties and generating diversity in both two and three dimensions. Because of theirnease of synthesis and similarity to biological soft matter, hydrogels have become a biomaterial of choice for generating 3D microenvi-nronments. In presenting these efforts within the framework of synthetic biology, we anticipate that future researchers may exploit syn-nthetic polymers to create microenvironments that control stem cell behavior in clinically relevant ways.