Scaffold-Free soft Tissue Engineering

Part of the Corr Group's research is the development of scaffold-free soft tissue engineering models. This embryonic-inspired approach to tissue generation utilizes micromolded, differentially-adherent growth channels to guide seeded cells into single, naturally-formed fibers. We have also developed a custom bioreactor to mechanically and electrically stimulate our fibers. The application of these stimuli during fiber development enables precise control over the structural and/or mechanical properties of the mature fiber.

The scaffold-free, embryonic-inspired technique we are exploring relies on a highly cellular microenvironment with little matrix presence to encourage direct cell-cell contact an native matrix production. Our approach has been successfully applied to synthesize long-lasting (> 21 day survival) individual tendon fibers with good mechanical properties. We note that key to single tendon fiber synthesis is early mechanical stimulation, e.g., intermittent cyclic uniaxial strain.

Changes in tendon fiber alignment and nuclear morphology in response to uni-axial loading.

Changes in tendon fiber alignment and nuclear morphology in response to uni-axial loading.

Current projects include evaluation of mechanical and biochemical stimuli on these engineered tendon fibers, namely characterization of the effects of these stimuli on parameters such as collagen content and cell nuclear morphology. We are also exploring adapting our approach for the development of single muscle fibers.

Laser Direct-Write bioprinting

We have developed a laser-based direct-write (LDW) bioprinting technique capable of patterning living cells, in a spatially precise manner, while maintaining cellular viability. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs.

Our work with this technique has thus far enabled the fabrication of 3D customizable core-shelled environments, which allow for controlled cell-cell contact, cellular proliferation and aggregation within the capsule. In this way, we are exploring the properties of development of cellular aggregates, formed naturally within the shelled environments by self assembling cell types.

We have also explored the creation of continuous 3D structures, such as microstrands, bifurcations, and rings, in which the architecture and composition can be prescribed at the individual microbead level. Thus, heterogeneous structures can be created, with different cell types at specific locations.