As a graduate student I plan to delve into the field of biomaterials with tissue engineering and drug delivery applications. My immediate goal as a graduate student is to design a degradable polymer that could be used for wound healing, tissue regeneration, and/or drug delivery. This fall semester I chose to work in Dr. Miriam Rafailovich’s lab because of her exciting work in biomaterials. The lab consists of an Interdisciplinary Research Group with a focus on the design of polymer thin film properties through precise control of interfacial structure. In biomaterials, there is a focus on the development of engineered surfaces for cellular adhesion and protein adsorption. An area of focus was the use of Gelatin, derived from collagen, to form hydrogels. Gelatin has both mechanical properties required for tissue growth, as well as the functional domains required fro cell binding. Understanding the supermolecular structure of this hydrogel is necessary for the encapsulation of cells for tissue engineering applications. These advances in polymeric biomaterials, which I intend to expand on, can lead to a new approach in tissue engineering as well as localized drug delivery.

Injectable Hydrogels have great potential for use as 3-D cell culture scaffolds in cartilage and bone tissue engineering due to their high water content, extracellular matrix, and porous framework that allow for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. Bioprinting is an emerging tissue engineering discipline because of its ability to print cell-laden hydrogels layer-by-layer according to a predefined, 3D model. The hydrogel-cell suspension is usually printed as a liquid solution and undergoes gelling, chemically or physically triggered, after the dispensing process. A problem that arises during bioprinting is shear stress. Upon dispensing, a shear stress is inevitable and could play a decisive role in cell biology. The level of shear stress is directly influenced by different printing parameters, such as nozzle diameter, printing pressure, and viscosity of the dispensing medium. In order to optimize the functionality of cells upon dispensing, these parameters need to be tuned accordingly. Depending on the cell type, the level of shear stress could enhance or be detrimental to cell function. For example, moderate shear stress can have an influence on stem cell differentiation but at excessive shear stress, the cells can be dispatched by disruption of the cell membrane. To prevent adverse cell response and printing-related cell death, it is essential to control the shear stress level.

Currently, I am working with Dr. Miriam Rafailovich to design a 3-D bioprinting system for tissue engineering applications. The system works where a liquid polymer loaded with various growth factors and cells is injected onto a substrate and self-assembles into a network suitable for cell growth. As stated above, upon injection, the cells are subjected to a shear force that could kill or affect functionality. My first goal is to determine the critical shear force that would harm a cell and then optimize the polymer properties to ensure that threshold is never reached. The cell types I will be using are dermal fibroblasts, which are adherent cells. These adherent cells would be subjected to a wall shear force since they are likely to bind to the surface of the dispenser. There are many parameters that could affect the amount of shear stress the polymer could induce on the cells upon injection. Viscosity, Molecular Weight, Volume Fraction, and Flow Rate all affect the amount of shear stress the polymer generates on the cells.

Once an optimal polymer is found, a bioprinting system can be implemented. The cells can be loaded with various growth factors and the proliferation of the cells in the polymer can be determined. Using the bioprinting system I can design scaffolds for tissue engineering and drug delivery applications. The goal of this project is to design a scaffold from the optimal polymer that can be implemented in vivo and induce tissue regeneration and localized drug delivery.