Restraint of the Differentiation of Mesenchymal Stem Cells By a Nonfouling Zwitterionic Hydrogel

The success of human mesenchymal stem cell (hMSC) therapies is largely dependent on the ability to maintain the multipotency of cells and control their differentiation. External biochemical and biophysical cues can easily trigger hMSCs to spontaneously differentiate, resulting in a rapid decrease of the multipotent cell population and thus compromising their regenerative capacity. In this work, we demonstrate for the first time that nonfouling hydrogels composed of pure poly(carboxybetaine) (PCB) allow hMSCs to retain their stem cell phenotype and multipotency, independent of differentiation-promoting media, cytoskeletal manipulation agents, and the stiffness of the hydrogel matrix. Moreover, encapsulated hMSCs can be specifically induced to differentiate down osteogenic or adipogenic pathways by controlling the content of fouling moieties in the PCB hydrogel. This work examines the critical role of nonspecific interactions in stem cell differentiation and highlights the importance of materials chemistry in maintaining stem cell multipotency and controlling differentiation.