Fig. 3.

Future engineered stem cell niches may be designed to mimic the dynamic native niche environment through incorporation of bi-directional feedback between encapsulated cells and their matrix. In one potential realization, (1) stem cells initially adhere to a matrix that (2) releases factor 1 at a specific time. (3) Factor 1 could be a growth factor that leads to stem cell proliferation and the accumulation of protease 1. (4) Protease 1 degrades specific regions of the matrix, which may lead to a change in stiffness, thus inducing stem cell differentiation. (5) Upon differentiation, cells alter their proteome and begin secreting protease 2. (6) Protease 2 triggers the cleavage of cell binding ligands, (7) thereby inducing cell migration and extension of processes such as axons and dendrites into the surrounding material. Listed below are several potential bi-directional response elements that could be designed into future dynamic matrices.