Patients suffering from large tissue defects due to conditions such as trauma, tumour resection and congenital malformations have limited and suboptimal treatment options. For example, autografts taken from the patient’s own body require sufficient volumes of healthy tissue, and donor site morbidity can result. Advanced manufacturing techniques combined with biologically compatible materials have been applied to the development of porous three dimensional implants with the potential to treat challenging medical conditions such as the repair of large, critically sized tissue defects. When seeded with cells and cultured in vitro, these structures provide a scaffold for the guided development of tissue while also creating the environment necessary for cellular proliferation, differentiation and the generation of extra cellular matrix.

Supplying cells with nutrients, removal of cell metabolic by-products and the application of appropriate levels of hydrodynamic stimuli is essential for viable tissue growth within the scaffold during culture. Managing these requirements has proven a considerable challenge when culturing large tissue scaffolds and irregular scaffold shapes commonly result in non-viable or irregular cell culture conditions beyond a periphery surface zone.

This program of research has developed methods that can be followed to create a culture system individually customised for specific tissue scaffold requirements. Pre-existing medical imaging data was used to generate the external shape of large osseous tissue scaffolds including calcaneus, femur, cranium and mandibular sections. These scaffolds have been used as the basis for the design of adaptable bioreactor systems consisting of customised transitional geometry between the scaffold and bioreactor system to control the flow of culture media through the scaffold. With this method, a standard bioreactor can successfully culture cells within one-off, patient-specific scaffolds. Computational fluid dynamics and experimental flow testing was used to investigate the permeability of the scaffolds and optimise the bioreactor designs. Final designs were developed into a functional perfusion bioreactor and tested with cell culture experiments to assess their feasibility and gain an understanding of their performance. The cell culture experiments show that these techniques can be used to design bioreactors capable of cell culture within thick, anatomically-shaped scaffolds that otherwise commonly result in a necrotic core of cells beyond a thin region of viability at the scaffold surface (up to a few millimetres). Furthermore, the methodology used here can be followed to developed tailored systems of in vitro culture for a range of different applications.