Title: Bottom-Up Tissue Engineering: Tendon Fiber Self-Assembly and 3D Laser Direct Write Bioprinting
Dr. Corr’s laboratory aims to understand the impact of various environmental and developmental stimuli on cell behavior and fate decisions, and to exploit these to improve functional tissue engineering, particularly in musculoskeletal soft tissues. This seminar will highlight the development and application of two bottom-up techniques used to inform and guide soft tissue engineering and regeneration: (i) scaffold-free fiber engineering, and (ii) gelatin-based laser direct write (LDW) bioprinting.
Dr. Corr’s scaffold-free approach utilizes directed cellular self-assembly and applied biophysical stimulation to harness the cells’ natural abilities to organize, create extracellular matrix, and form fibers (e.g., skeletal muscle, tendon, ligament), in a method that mimics key aspects of embryonic tissue development. Cellular growth is guided using differentially-adherent growth channels, and a custom electromechanical bioreactor precisely delivers prescribed mechanical strain and/or electrical stimulation to the fiber as it forms. This provides novel insight to the influence of the magnitude and timing of environmental cues (e.g., biophysical stimuli) on fiber formation, the elaboration of matrix/structure, and evolution of biomechanical function.
Gelatin-based LDW is a CAD/CAM bioprinting technique able to “print” living cells for the creation of spatially-precise cellular cultures and co-cultures in 2D. It is uniquely able to target and transfer cells, or other biopayload (e.g., soluble factors, proteins, biomolecules), to a substrate, with spatial precision, and can do so while preserving stem cell pluripotency. Dr. Corr’s lab extended this technique to create and pattern 3D hydrogel microbeads, in which the size is controlled by the beam diameter of the laser. Microbeads provide a custom-engineered 3D microenvironment for the cells, and can be printed in layer-by-layer fashion to create thick constructs in which the composition is prescribed with bead-level fidelity. Printed microbeads can be further processed to create spherical microcapsules and tubular microstrands. Taken together, these bio-additive fabrication techniques can create 2D and 3D cellular structures, with customized composition and architecture, for use in tissue engineering and in vitro diagnostics. Examples in directing stem cell fate decisions, creating size- and shape-controlled 3D aggregates (e.g., EBs, tumor spheroids), and heterogeneous 3D tumor models will be discussed.