STEREOLITHOGRAPHY PRINTER

My proposal aims to develop a stereolithography 3D printing platform for the rapid fabrication of low-cost material systems in the laboratory with micro-scale features yet centimeter-scale objects. A digital micromirror device (DMD) will be used to project patterns with spatial resolution down to 20 μm onto a layer of photo-crosslinkable hydrogel. DMD is a micro-electro- mechanical system that enables a user to control over one million micron-sized mirrors to turn on or turn off in a time of the order of one thousandth of second. Large-scale 3D objects will be fabricated by stitching projected images over a 3cm x 3cm area, while incorporating an axial stage for controlling the height of the construct. This allows the entire construct to be fabricated in the bulk fluid without any intermediate processing steps. The optical set-up will be optimized for precise patterning of the projected images onto the ink.

         

DISEASE-ON-A-CHIP

The cancer microenvironment is highly complex and highly dynamic, with distinctive key features present at each of the different stages of the disease. In particular, the large-scale growth of a tumor ultimately requires a blood supply, which leads to abnormal vascularization in the tumor spheroid when compared to healthy tissue. Despite significant advances in conventional cell cultures and animal models, they do not necessarily replicate tumor microenvironments that involve sprouting vasculature and tissue stiffness that affects the behavior and directionality of the cancer cells. I hypothesize that the use of the proposed platform will allow fabrication of a clinically relevant tumor model to replicate the structural complexity of tissue vasculature. This may offer an unprecedented examination of early cell migration and drug diffusion induced by the gradient of tissue stiffness. The DMD platform will be used to bioprint normal and tumor vasculature patterns in methacrylated gelatin, loaded with fibroblast and breast cancer cells, respectively. First, the bioprinted tumor model will be inserted into a chip design and subjected to media circulation as a form of closed bioreactor. Second, the chip will be used to stimulate pre- vascularized cell-loaded gelatin with breast cancer cells and optimize the construct composition to enhance vascularization. Third, fluorescence microscopy will be used to observe cell migration for different degrees of gelatin stiffness. This tumor-on-a-chip holds significant potential for drug research and development.

MECHANICS OF EXTRUSION

3D Printing techniques have been flourished in the fabrication of advanced scaffolds for tissue engineering and regenerative medicine. In addition to design and development of bioprinting platforms, bioink formulation should be optimized for the application of interest. A proper optimization of bioink formulation requires an inclusive understanding of bioprinting process. In this project, we will itemize the governing parameters in extrusion based bioprinting process: printing resolution and instability. Assuming known geometry and constant flow rate, we try to describe the behavior of a general viscoelastic fluid. This would lead to derivation of the relations between fluid properties and printing resolution as well as threshold of instability. We then develop a printability map based on fluid viscosity, input flow and nozzle size. This project will help researchers in understanding current challenges of bioprinting and selecting the proper approach.

DISEASE-ON-A-CHIP

Cartilage tissue engineering is of significant interest in regenerative medicine because damaged articular cartilage lacks the ability to self-repair. Recent studies focus on induced pluripotent stem cells (iPSCs) that possess an extraordinary capacity to differentiate into different cell types. Mechanical stimulations have been shown to enhance iPSC differentiation into chondrocytes; however, designing microenvironments that control iPSC differentiation and plasticity is still challenging. ECM-derived hydrogels provide an instructive microenvironment for chondrogenesis. I hypothesize that mathematically defined periodic mesostructures will provide biomechanical tuning in cell-laden constructs under cyclic loading. This project will initially involve designing negative-stiffness honeycombs, introduced by Correa et al. (Rapid Proto J 2015), which exhibit relatively large positive stiffness followed by a region of plateau stress as the building blocks buckle, with full recovery after compression. This can be elicited by a curved beam structure in regular honeycomb structures. The mechanism underlying energy-absorbing behavior is elastic buckling rather than plastic deformation (i.e., full recovery). The proposed platform will then be used to fabricate 3D methacrylated gelatin-based constructs, loaded with pluripotent stem cells. Next, the construct will be stimulated by cyclic loading, at physiological deformation and frequency, to accelerate the kinetics of the stem cell differentiation. Finally, computational simulations will be used to correlate the relations between differentiated stem cell markers and structural pore size ranging from microns to millimeters.

Research Projects

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