Novel strategies to encode engineered living matter with self-feeding properties

The field of tissue engineering aims to replace or repair damaged or diseased tissue, typically by combining cells with various biomaterials and growth factors. Although a plethora of approaches have been developed and researched, the field has so far lacked the impact it promised. One of the main challenges for translating engineered tissues towards patients is the upscaling of these structures from small lab to clinically relevant sizes. Specifically, upon implantation, engineered tissues typically lack functional vascularization that offers continuous nutrient and oxygen supply. This typically results in the development of ischaemia that leads to a necrotic core and hence implant failure.
This thesis highlights the ability to preserve cell viability and function under oxygen deprived conditions similar to those found in large engineered tissues. As typical nutrients, such as glucose, are characteristically small and hydrophilic, the scientific chapters represent the developmental path of a nutrient releasing system to be integrated into engineered tissues and to provide these structures with self-feeding properties. The incorporation of glucose into a hydrophobic carrier enables controlled and sustained release into the surrounding, which is build upon on by 3D-printing the first of its kind mechanical life support.
Lastly, the work on the previous self-feeding approaches led to the discovery of glycogen as potent and novel glucose releasing system, with straightforward integration into tissue engineering applications. This cell-mediated nutrient release ensures glucose availability for the cells at the time of need.

To summarize, this thesis introduces novel self-feeding approaches with the aim to give tissue engineered constructs the chance to “grow up” towards clinically relevant sizes.