This two-year proposal examines the feasibility of using self-assembly to synthesize biomaterials that have porous three-dimensional (3D) architectures. Development of many envisioned biomedical devices, including scaffolds and stents for tissue repair, bioreactors for the expansion of cells ex vivo, and microparticles for controlled drug delivery, will require methods to precisely control the pore sizes and geometries of biomaterials. Current methods for 3D fabrication often rely on machining or layer-by-layer lithography, and are thus limited in speed, resolution, or applicability to soft materials. To address these limitations, the proposed work uses directional, selective forces between microscale liquid films to effect assembly of 3D structures. This broadly applicable strategy for materials synthesis affords control over pore sizes and geometries at the 1- to 1000-micrometer size scale, and thereby enables the synthesis of biomaterials that have complex internal structure. Specifically, this work will target the assembly of materials suitable as bioreactors that can transport and exchange gases or solutions throughout an engineered tissue construct. These self-assembled materials will have large surface area-to-volume ratios and a grid of internal channels 10-50 micrometers in width. The self-assembling process will rely on capillary forces between 10- to 100-micrometer-sized metallic polyhedra to induce the aggregation of polyhedra into porous scaffolds. Replication of these open geometries in inert metals, degradable polymers, and type I collagen gels will yield model tissue constructs that possess a set of channels for internal perfusion. This work will create three types of bioreactors: (1) collagen gels that have ordered arrays of interconnected channels, (2) porous collagen gels whose channels are lined by a metallic support, and (3) porous collagen gels whose channels are lined by human umbilical vein endothelial cells. Each reactor will consist of human dermal fibroblasts embedded within a gel; for each type of reactor, this work will determine how network geometry and perfusion rate affect the maximum sustainable density of fibroblasts and their rates of proliferation and apoptosis.
| Golden, Andrew P; Tien, Joe (2007) Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 7:720-5 |
| Nelson, Celeste M; Tien, Joe (2006) Microstructured extracellular matrices in tissue engineering and development. Curr Opin Biotechnol 17:518-23 |
