Inkjet printing of cellular sheets and gelation mechanisms

This fellowship proposal aims to bring together several different research disciplines to address a current need in reconstructive surgery. Nasal reconstructive surgery is not confined to cosmetic enhancement and is often required as a result of trauma, disease or cancer treatment. Removal of cancerous tissue and severe injury can lead to severe deformation of the patients features post operation. Current treatments of the nasal and oral cavities to alleviate this problem utilise transplanted tissue taken from other non-mucosal areas of the body. These grafts are compatible with the patient's immune system but lack the qualities of normal mucosal tissues leading to poorer clinical outcomes characterised by scarring and drying. This research aims to engineer a mucosal epithelium graft using the patients own cells. Very thin skin-like layers can be generated in a laboratory environment through the use of thermo-responsive surfaces. These surfaces are coated with a special polymer which allows cells to stick onto it at body temperature (37?C). Over time the cells stuck to this surface will produce their own support matrix binding them tightly together to form a sheet. When the cell sheet is ready the temperature is lowered and the special polymer becomes less favourable for cell attachment and allows the sheet to be peeled off in one layer. Current methods of creating patterned cell sheets are limited to time-consuming chemistry.My previous research has shown that cell suspensions can survive being printed using an inkjet printer similar to that used in an ordinary office. Printing is a rapid and efficient way of patterning a surface. Using the printer we plan to deposit cells onto the thermo-responsive surfaces in defined patterns so we can create a skin sheet containing several types of cells and fabricate a more accurate mimic of natural tissues. Real tissues are made of cells and extracellular matrix. The extracellular matrix is a gel like substance containing many vital nutrients and biomolecules. In order to create a more natural mimic of the tissue structure this fellowship will look at ways of including gels into the fabrication of the cell sheets. The addition of a gel will also help to improve the mechanical properties of the cell sheet. Improved mechanical strength is important for future surgical use such as suturing. In order to print a gel we need to engineer a new method of delivering a chemical cross-linker. This system will incorporate an inert chemical into the gel which will be activated at a specific temperature allowing us to control exactly when the gel will set.