Designing synthetic materials to control stem cell phenotype

This review discusses how stem cell behavior is manipulated using synthetic materials. Ligands have been designed to emulate the natural extracellular matrix, cell-cell contacts, and growth factors. Fate determination of the stem cells is regulated by material architecture and mechanical properties. Synthetic material systems are specifically designed to interact with cells on different length scales (e.g. macro vs cellular). Thus, they replicate the elements of natural stem cell niches (micro-environment needed to sustain self-renewal and control differentiation). However, synthetic materials differ from natural because they have the potential for improved control, repeatability, safety and scalability. Several classes of synthetic materials have been created to control stem cell phenotype: natural polymers (like mammalian ECM), synthetic polymers (like polyacrylamides), inorganic materials, and self-assembling peptides. Whichever class is used, the material must be processed and functionalized for specific clinical applications. Important material properties include ligand identity, presentation (conformity/orientation), and density. Optimizing these parameters creates materials that resemble the natural environment of the stem cells and allows for controlled mechanical properties.

Self-renewal and differentiation mechanisms are sensitive to many ligands/combinations of ligands: adhesion ligands from ECM, ligands from neighboring cells, and immobilized growth factors. Once a set of ligands is selected, it must be conjugated to the material for proper orientation. The way a material is organized and structured on the nanoscale (aka material architecture) is known to control cell signaling and organization. The geometry of the cellular interface with the material is a major factor in determining ligand engagement, molecular diffusion, and force transmission. Material architecture also determines bulk mechanical properties at larger scales. Both 2D and 3D architectures have been used for stem cell cultures. For 3D scaffolds, there are 3 predominant types: porous solids, hydrogels, and nanofibers. Material mechanics is largely determined by material's composition, water content, and structure. These affect intermolecular forces and stress distributions. Common techniques to change mechanical properties include altering molecular composition/connectivity, thermal processing, and creating porous composites. Mechanical properties affect cell migration and proliferation. Tensional homeostasis with the micro-environment (via integrins) causes cytoskeletal rearrangements and changes gene regulation pathways. The elastic modulus of culture material can alter or maintain human stem cell phenotype. Viscoelasticity is another mechanical property that may affect stem cell phenotype, but its effect is not fully known yet.

I chose this paper because I believe that studying how to manipulate stem cells is crucial, particularly if we want to successfully utilize stem cells in therapeutic applications. This paper discusses several properties that play significant roles in directing stem cell phenotype, but concludes that much work needs to be done in the future to realize the full clinical potential of stem cells.

-Rustin