3D Cell migration
Cell migration is a key function of multicellular organisms in homeostasis, regeneration of injured tissues and immune responses. Migration of mesenchymal cells on flat substrates such as glass or tissue culture treated polystyrene is well characterized as lamellipodial migration, while migration in 3D environments such as the human body is not well known. In our lab, we use nanofiber scaffolds to investigate how cells migrate in nanofiber-based tissue engineering scaffolds. These 3D environments also impact our understanding of cell migration mechanisms due to an ability to control the physical environmental parameters that is not possible with natural extracellular matrix systems.
Tendon tissue engineering
The cell microenvironment, including adhesion mechanisms and responses of cells to biomaterials, plays a critical role in cell proliferation, differentiation, and growth. Previous PhD student Brittany Banik developed a tendon bioreactor targeted for tendon tissue engineering applications, focusing on harnessing bioinstructive cues through nanofiber diameter and bulk scaffold architecture to encourage cells to move towards a tenogenic lineage. Using a unique electrospun scaffold with a Chinese-fingertrap design to create an improved tendon scaffold which mimics the anisotropic stress-strain curve of natural tendon, we have seen increased scaffold mechanical properties, improved scaffold integration and performance, and directed mesenchymal stem cells to the tendon lineage. This work has the potential to be utilized in not only tendon tissue engineering but also in ligament and vascular regenerative medicine.
Cartilage tissue engineering
Cartilage injuries, such as a torn meniscus, are extremely common, but healing cartilaginous tissue is difficult due to a lack of vascularization. Our lab is particularly interested in the potential of 3D printing to improve scaffold designs that can be utilized to regenerate the meniscus. 3D printing nanofibers provides increased control of nanofiber orientation and layering and allows for the creation of curved nanofibers that can mimic the shape of a native meniscus. By using multiple extrusion heads, we can combine printed nanofibers with controlled deposition of hydrogel materials and create a composite material with desirable properties.
Enthesis Tissue Engineering
Integration of regenerated cartilage with bone has yet to be successful, and this integration is critical for cartilage to provide the intended support and cushion. The transitional region where cartilage and bone meet is called an enthesis, although the term can also refer to regions where tendon, ligament, or fascia join bone as well. Current lab work focuses on generation of a ligament enthesis through the use of electrospun nanofiber scaffolds created from silk fibroin.
Systems mechanobiology
Mechanobiology is a relatively young field at the intersection of biophysics and biology. It is focused on describing of the impact of physical forces such as tension, geometry, shear flow, etc. on cell behavior, as well as developing our understanding of the mechanisms by which these signals are detected and transduced and effect changes in protein and gene expression. Our lab is focused on characterizing the structure and composition of the cytoskeleton (the ‘mechanical state’) of mesenchymal stem cells attached to various surfaces and determining the differentiation state each surface promotes. Through this work, we aim to draw connections between the mechanical state and differentiation state, uncover signaling pathways that connect these two aspects of cellular behavior, and utilize large datasets to construct statistical models that can be used to predict cell behavior.