Bioengineering biomaterials to assess signaling in response to mechanosensing
Hydrogels and fibrosis
Despite the ubiquitous role of fibrosis in tissue dysfunction arising from aging and disease, no representative in vitro model of the fibrotic microenvironment exists. Fibrosis is characterized by excess extracellular matrix deposition that stiffens the cellular microenvironment. To model fibrosis in vitro, cell culture substrates that permit quantitative, dynamic tuning of matrix mechanics and composition are necessary. Fibrotic stiffening occurs in a wide range of tissues, including skeletal muscle. Muscle stem cells (MuSCs) are responsible for maintaining and repairing muscle throughout life and are acutely mechanosensitive, losing their stem cell potential when cultured on stiff substrates. Thus, the stiffened, fibrotic microenvironment may contribute to the diminished regenerative capacity of aged MuSCs. Our current goal is to develop an in vitro model of tissue fibrosis based on dynamic hydrogel biomaterials and to employ this model to identify molecular mechanisms of MuSC mechanosensing that are implicated in MuSC dysfunction in aging.
Hydrogels that soften on demand
We use human-derived cells in combination with novel biomaterials and engineering techniques to deconstruct and reconstruct the cellular and architectural complexity of skeletal muscle in a dish to provide a platform for studying fundamental processes that affect skeletal muscle function in aged tissue. Using biomaterials with tunable mechanical properties combined with microfabrication techniques we can recapitulate features of muscle organization and neuromuscular function in a dish. These organ-like systems offer human-derived platforms for mechanistic study of muscle biology as well as drug testing.