Membrane supported scaffold architectures for tissue engineering

Tissue engineering aims at restoring or regenerating a damaged tissue. Often the tissue recreation occurs by combining cells, derived from a patient biopsy, onto a 3D porous matrix, functioning as a scaffold. One of the current limitations of tissue engineering is the inability to provide sufficient nutrient and oxygen supply in developing 3D in-vitro culture. In human body the vasculature is embedded into almost every tissues and organs. They transport blood, and thus nutrients and waste products, to and from almost any part of the body. It is a critical template for the exchange of gas, nutrients, cells or molecules and a regulator of tissue development. Insufficient vascularization within the construct results in nutrient limitations, which in-turn results in suboptimal integration of, and cell death in tissue engineered constructs. This thesis explores a new approach by integrating semi-permeable porous hollow fiber membrane in to tissue engineered scaffolds to mimic capillary network. The rationale of this method is that the hollow fibers integrated within the tissue engineered scaffolds would supply required nutrients and gases through the walls of the fiber during in-vitro perfusion bioreactor culture. Furthermore, the same approach is used to develop 3D multilayer tissue using bottom-up process by rolling pre-seeded electrospun (ES) sheets around multibore hollow fiber. The rolling of pre-seeded ES sheet to form multilayer constructs achieves uniform cell distribution in the scaffold and has a marked potential to form functional tissue composed of multiple cell types. This thesis also presents the development of biodegradable hollow fiber membrane of poly (L-lactic acid) (PLLA), suitable for nutrient perfusion and illustrates the effect of scaffold surface structure and curvature which plays a critical role in cell adhesion and proliferation in dynamic culture conditions.