Stem Cell Engineering Approaches to Additive Bioas-sembly

The extracellular matrix surrounding cells in tissue is a dynamic composite material, where the presentation of biophysical and biochemical information directs functional bioactivities. My laboratory is interested in how the properties of the extracellular matrix guides cell decision making and have developed a suite of engineered extracellular matrices to probe the biophysical and biochemical basis underlying cell programming and re-pro-gramming. Here I will discuss how engineered model systems that better recapitulate in vivo biology than tissue culture plates can be leveraged to explore how cells receive and integrate sig-nals to specify lineage. First, I will show how combinatorics can serve to identify hydrogel substrates that prime a thera-peutic acitivity in mesenchymal stromal cells (MSC). MSCs adherent to extracellular specific matrix conjugated hydrogels show elevated secretion of pro-angiogenic and immunomodu-latory cytokines and this activity is retained after cryopreserva-tion and storage. Next, I will demonstrate a new bioprinting ap-proach within a cell-laden bath of extracellular matrix colloids, where MSCs within the bath proliferate and differentiate when in proximity to bone-like structures. These and other composite hydrogel-based model systems are changing the way in which fundamental biological questions can be probed, which will aid our understanding of biological processes while revealing new design parameters for regenerative biomaterials.