Tissue engineering research has opened a new chapter in modern medicine since it emerged as a mainstream research field in the early 90s. Until now, however, effective strategies to fully emulate the complexity of natural tissue remain elusive. One of the key features in the development of complex tissue structures is the presence of morphogen gradients during development. In nature, from squid beaks to human teeth, gradients are preserved in many structures after evolution. In a living organism, gradients play an essential role in defining the physiological function. The formation of these gradients is often largely dictated by an anisotropic distribution of different morphogens present during development. The spatial difference in concentration of different morphogens results a spatial variance in cell signalling, patterning the development of tissue and leading to the formation of heterogeneous structure.
Although these principles of development are well-established, the overwhelming majority of in vitro engineering strategies use uniform scaffolds and spatially invariant growth factor delivery to produce homogeneous tissue constructs. It is clear that more sophisticated fabrication processes are required to replicate the native complexity and fulfil the functional requirements of tissue grafts. A few material strategies have been developed that can heterogeneously deliver biological or mechanical cues; however, most of them are limited by complex fabrication procedures or restricted compatibility with different material systems.
By establishing signaling factor gradients within tissue engineering scaffolds, the formation of heterogeneous tissue interfaces can be achieved. This thesis will demonstrate two gradient casting strategies to emulate physiological gradients, exploiting magnetism and buoyancy to distribute growth factors. These strategies are shown to be capable of establishing gradients in different materials, and are used to engineer osteochondral tissue. The strategies proposed in this research are designed to be widely applicable and easy to reproduce. It is hoped that these strategies may be adapted and tailored for wider use by the tissue engineering field, allowing development of complex, functional tissue by mimicking the processes used by nature.