Designing synthetic materials to control stem cell phenotype

Abstract

The micro-environment in which stem cells reside regulates their fate, and synthetic materials have recently been designed to emulate these regulatory processes for various medical applications. Ligands inspired by the natural extracellular matrix, cell-cell contacts, and growth factors have been incorporated into synthetic materials with precisely engineered density and presentation. Furthermore, material architecture and mechanical properties are material design parameters that provide a context for receptor-ligand interactions and thereby contribute to fate determination of uncommitted stem cells. Although significant progress has been made in biomaterials development for cellular control, the design of more sophisticated and robust synthetic materials can address future challenges in achieving spatiotemporal control of cellular phenotype and in implementing histocompatible clinical therapies.

Figure 1. Design parameters for engineering synthetic stem cell materials

Ligand identity, density, and presentation from the material surface dictate interactions with cell surface receptors to alter cytoskeletal linkages and intracellular signaling pathways. Receptor-ligand interactions are further modulated by material architectures, which provide a two-dimensional (e.g. flat surfaces, micro-porous solids) or three-dimensional (e.g. nanofibers, hydrogels) microenvironment for cellular engagement. Also, the elastic and viscoelastic properties of the material determine the interplay between cell and material mechanics. Collectively, these parameters define the context for stem cell self-renewal and differentiation in a similar fashion to their native niches. Graphs schematically depict mechanical properties: elastic properties via a stress (σ) − strain (ε) plot and viscoelastic properties via a complex modulus (G*) − frequency (f) plot.