Development of Next Generation 3-Dimensional In vitro Soft Tissues Models for Biomaterial Testing: Controlling Construct Properties with Fluid Flow

Pre-clinical biomaterial development and testing have traditionally relied on 2D in vitro, or complex in vivo assays. It is essential for the cell environment to match the natural tissue in terms of matrix density, architecture, components (including stress/strains) for tissue models to behave in a natural manner. The aim of this project is to improve existing in vitro models for the biomaterial testing. Plastically compressed collagen hydrogels were used to create a simple and accessible 3D model. Improvement in hydrogel stiffness was achieved using pre-crosslinked, polymeric collagen, as a starting material. Hydrogels were formed by blending polymeric and monomeric collagens, which delayed the aggregation of collagen fibrils, and enabled cell incorporation at physiological pH. Plastic compression of the novel hydrogel resulted in stiffer constructs; however, during compression, cells were exposed to reversible (i.e. using mobile macromolecules) increases in cell-damaging fluid shear stresses. In the material degradation model, it was found that the release rates of PLGA degradation products were influenced by cells in the collagen matrix; and differed significantly between 2D (24 hours) and 3D (7 days) models. Imaging of cells cultured within the biomaterial also demonstrate the up-take of biomaterials within cells within the model after 10 days in culture. Nanoparticle drug delivery via hyaluronan nanoparticle (HA-NP) was im-