Final Report Summary - 3D-E (3D Engineered Environments for Regenerative Medicine)
The objective of this project was to develop a unified, underpinning technology for novel, complex and
biomimetic 3D environments for the control of tissue growth. These advances were then employed in research into therapies for the specific areas of breast cancer, cardiac disease and blood disorders.
Ice templating is an effective method of producing porous macromolecular scaffolds. A solution or suspension of chosen macromolecules is frozen to form an interpenetrating network of pure ice crystals surrounded by the “rejected” solute. Ice crystals are then removed by sublimation, leading to the formation of a porous scaffold templated by the original ice structure. To enhance the structural stability, chemical and/or physical cross-linkers are introduced. Hence ice templating followed by cross linking provides a base technology for the production of 3D cell culture environments.
We established the relationships between freeze drying thermal conditions and the resulting architecture of the scaffolds using experimental and finite element modelling approaches to create and control anisotropy. Our percolation analysis of X-ray micro tomographic data sets allowed the first full characterisation of the relationships between scaffold interconnectivity and cell invasion. We studied composition effects, explore the ablation of integrin recognition motifs from crosslinking and designed peptide functionalisation strategies which we proved could control cell binding. Self-crosslinked blends exploiting polyelectrolyte interactions were considered, and the multi-scale responses of the scaffolds to stress investigated. The multiple levers to adapt the environments were used to develop three dimensional environments for cells in cardiac repair, mammary gland mimics for breast cancer research and diagnostics, and bioreactor applications for blood disorders.
biomimetic 3D environments for the control of tissue growth. These advances were then employed in research into therapies for the specific areas of breast cancer, cardiac disease and blood disorders.
Ice templating is an effective method of producing porous macromolecular scaffolds. A solution or suspension of chosen macromolecules is frozen to form an interpenetrating network of pure ice crystals surrounded by the “rejected” solute. Ice crystals are then removed by sublimation, leading to the formation of a porous scaffold templated by the original ice structure. To enhance the structural stability, chemical and/or physical cross-linkers are introduced. Hence ice templating followed by cross linking provides a base technology for the production of 3D cell culture environments.
We established the relationships between freeze drying thermal conditions and the resulting architecture of the scaffolds using experimental and finite element modelling approaches to create and control anisotropy. Our percolation analysis of X-ray micro tomographic data sets allowed the first full characterisation of the relationships between scaffold interconnectivity and cell invasion. We studied composition effects, explore the ablation of integrin recognition motifs from crosslinking and designed peptide functionalisation strategies which we proved could control cell binding. Self-crosslinked blends exploiting polyelectrolyte interactions were considered, and the multi-scale responses of the scaffolds to stress investigated. The multiple levers to adapt the environments were used to develop three dimensional environments for cells in cardiac repair, mammary gland mimics for breast cancer research and diagnostics, and bioreactor applications for blood disorders.