Biomimetic In Vitro Systems
One of our main interests is in using ideas from tissue engineering and multi-scale mechanics to engineer in vitro models of tissues. Two particular applications of interest are with respect to cutaneous wound healing and scar formation and to traumatic joint injury and contracture.
We have developed several 3D in vitro platforms for observing and quantifying dynamic cell-cell and cell-matrix interactions that arise during the remodeling process in response to both mechanical and chemical cues. These systems typically consist of fibrin and collagen gels embedded with cells isolated from fibrotic and non-fibrotic tissue, such as rabbit joint capsule fibroblasts (RJCFs). Time-lapse images acquired at multiple positions are later analyzed to provide quantitative data on cell force generation, migration, collagen production, and other ECM remodeling processes over a wide field of view. At the end of the experiment, the gels are then extracted for qPCR, histology, or protein quantification.
In addition to biochemical cues, mechanical cues inform and drive cellular behavior. These cues can from the geometry and material properties of the local environment, or from forces transmitted through the tissue from the outside surroundings, or from traction forces exerted by neighboring cells.
Multi-scale Mechanical Interactions
Multiscale mechanical interactions are scale-spanning physical interactions between cells, the extracellular matrix (ECM), and the tissue, and they are critical to all phases of a tissue’s life cycle (i.e., development, growth, homeostasis, aging, and disease). These dynamic and reciprocal interactions are inherently complex and produce emergent behaviors that cannot be easily understood using reductionist approaches. It is therefore essential that a theoretical framework exists that can incorporate data and observations from different experiments into a unified picture so that basic principles of mechanobiology can be understood and used to direct tissue remodeling.
Schematic illustrating the role that multi-scale mechanical interactions play in directing tissue remodeling
|The mechano-chemical feedback loop that drives tissue remodeling and wound healing.|
Synthetic biology is a new area of interest for the group that has been driven by undergraduate interest in the annual iGEM competition.