Kevin E. Healy
Jan Fandrianto Distinguished Professor in Engineering
Departments of Materials Science and Engineering, and Bioengineering
University of California at Berkeley

Highly regulated signals in the stem cell microenvironment such as matrix stiffness, ligand adhesion density, growth factor presentation and concentration, and tissue architecture have been implicated in modulating stem cell differentiation, maturation, and ultimately tissue function. Therefore, for applications spanning human pluripotent stem cell (hPSC) expansion and differentiation to tissue biofabrication it is desirable to have independent control over these biochemical and mechanical cues to analyze their relative and combined effects on cell function and tissue formation. Accordingly, we have developed synthetic ECM (sECM) hydrogels, in which biophysical and biochemical properties are tailored to specific tissue types, defined as “design for optimal functionality”. We have also explored alternative sECM designs, defined as “design for simplicity,” in which a deconstructed, minimalist sECM is employed and biology performs the customization in situ. This presentation will discuss our progress in developing: 1) synthetic polymer interfaces for the expansion of hPSCs in defined media; and, 2) in situ forming sECM hydrogels, with growth factor sequestering capacity, as potential bioinks and as assistive matrices for transplantation of hPSCs into diseased or damaged tissue. These synthetic microenvironments have great potential for overcoming major bottlenecks for tissue biofabrication and improving the long-term results of regenerative therapies.

Bioinspired Polymer Networks for Stem Cell Expansion and Tissue Manufacturing.