UC San Diego

Techniques for cellular encapsulation within three-dimensional (3D) structures, such as bioprinting and patterning methods, play an important role in creating complex and hierarchically organized tissues, as well as when studying cell-cell and cell-matrix interactions. To this end, advances in technologies have enabled development of methods to generate such 3D structures. We describe an easy-to-use photopatterning method involving photomask and a simple fluorescence microscope. This method is adapted to generate homogeneous and co-culture tissue constructs. Additionally, we extend this approach to establish a system to quantitatively study cancer spheroid growth. We developed a method combining the photomask-based 3D photopatterning technique with microfluidics technology to encapsulate a cancer spheroid within a patterned hydrogel embedded with fluorescent particles, monitor the cancer growth, and quantify the corresponding relative changes in the mechanical properties of the surrounding extracellular matrix (ECM). In this method, we applied hydrostatic pressure to compress the acellular and cell-laden gelatin methacrylate (GelMA) structure to detect volumetric strains. In the case of cell-laden GelMA hydrogel, we applied hydrostatic pressure at different culture timepoints, and recorded the changes in the local volumetric strains and compared it to a finite element simulation. We assess the possibility of this approach to deduce the approximate changes in the material properties during the cancer spheroid growth.