While stem cell differentiation in 3D recapitulates aspects of embryonic development and stem cell niches, current approaches lack spatial and temporal control of morphogenesis and patterning. We are working to engineer methods that enable precise control of the biophysical and biochemical environment.
Outside-in Engineering- Recent studies from our group have demonstrated that modulation of the stem cell culture environment impacts pluripotency and differentiation via indirect and direct effects on aggregate formation and size, as well as intercellular and matrix adhesions and soluble morphogen expression. Therefore, ongoing work aims to define the role of fluidic parameters (transport, shear), morphogen composition and metabolite profiles in regulating cell fate, particularly in 3D stem cell aggregates. We have also explored techniques for manipulating the stem cell environment via microencapsulation of aggregates in hydrogel materials, which enables tunable changes in mechanics and permeability via modification of material properties.
Inside-out Engineering - We have also successfully developed techniques for engineering the stem cell microenvironment from the inside-out using biomaterial microparticles that are directly incorporated inside the aggregates of cells. The biomaterial particles, often in the form of microspheres, can be engineered to temporally control the delivery or presentation of morphogenic factors locally. Depending upon the choice of materials and morphogens, this approach can be broadly used to direct stem cells to various differentiated cell fates. We are working in collaboration with polymer chemists, biomaterials scientists and engineers to develop novel delivery vehicles and related technologies capable of improving the controlled presentation of morphogens to stem cells undergoing differentiation.