Funded Project Summary:
Professor Ruth Cameron’s team at the University of Cambridge was recently awarded £63,980 to take the following project forward:
Directing respiratory organoid development via tailored three-dimensional macromolecular environments
Our aim is to produce alveolar organoid structures in highly defined 3D structures. This will allow us to transition away from current spherical organoid systems, typically cultured using Matrigel, to a 3D system that more appropriately reflects tissue organisation. We propose to design ice –templated, collagen- and elastin-based, porous environments to supply the spatial, mechanical and biochemical cues of native tissue.
The self-organisation of alveolar-derived co-cultures in 3D cell scaffolds will be studied in structures possessing a range of density, porosity and composition, identifying conditions that promote cellular organisation to closely match native lung. Critically these tailorable structures permit systematic decoupling and assessment of extracellular matrix (ECM) attributes that are crucial for lung cell organisation which is not possible using current homogeneous supports (e.g. transwell inserts and Matrigel) or decellularised lung tissue. Instead our system will allow the study of cells in a native-ECM structure with systematically altered properties to address specific, hypothesis-driven, questions such as the influence of architecture, biochemical cues and stiffness.
We will use ice-templating methodology to fabricate highly porous, completely interconnected 3D structures of biologically-derived collagen I and elastin with precisely tailored architectural cues. These are highly cell conductive and can be used for the formation of complex self organised cell structures, developed from multiple cell types. We will explore the effects of pore architecture, mechanics, the ratio of collagen and elastin and the use of synthetic peptide motifs to direct the cellular phenotype.
This project will provide proof of concept of a system replicating lung cell self-organisation with the flexibility to decouple, assess and address environmental attributes crucial for lung development and disease progression.