3D Bioprinting Engineering Artificial Respiratory Tract Tissue

The proposed project fits in Priority Area: Leading Edge Healthcare
Background:
There is a need to develop and improve human relevant tools enabling the study of mechanisms not yet fully understood in human biology. Current in vivo models almost exclusively utilise non primate animals which are limited by frequent poor correlation between human and animal systems. The ideal model would allow the direct interrogation and comparison of genetically equivalent human tissues under different experimental conditions. Advances in growing human tissues ex vivo, have led to the development of ex vivo human organ culture. To date this has focused on generating human organs for transplantation. However, the techniques developed also offer the potential to revolutionise in vitro studies of human biology. Whilst decellularised scaffolds hold promise for transplantation, the requirement for human or animal tissue to generate scaffolds limits the broad scale application of the technology to other areas such as science discovery.
3D bio-printing is the process of creating spatially-controlled cell patterns, in which the behaviour of biological tissues can be reproduced. This ideally extends to printing complete, viable organs for in vitro model, tissue repair and organ transplant. Printing viable organs is not possible as of yet, as organs are very complex. Most printed tissue constructs are not viable for very long, printable cell-laden bioink and perfusion of the construct after printing are still open issues. Despite challenges, the functioning micro- organs have been produced by 3D bioprinting, promising for further development.
Research Plan:
The aim of this project is to develop and optimise engineered artificial scaffolds amenable to ex vivo human respiratory tract organ culture. We propose to investigate approaches to enable the growth of organs in test tubes, by making use of advances in 3D bioprinting technologies with an ultimate goal to significantly reduce/entirely replace the use of animal organs in research. Specifically the programme of research would consist of:
(i) Printing artificial human epithelial tissue
1.2 IMPACT SUMMARY (Up to 1500 characters)
1.3 DATA SHARING (Up to 2000 characters)
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The first step is to develop printable hydrogels and cell loaded bio-ink for fabricating airway tissue. Artificial airway with multicellular structure consisting of fibroblast stroma with epithelium will be printed and cultured for growing a fully differentiated epithelium in air-liquid interface models. Cellular self-assembly within printed scaffold will be studied and compared with human lung scaffolds from donor tissue through histological analysis and biomarker profiling.
(ii) 3D printing miniaturised whole organ scaffolds
The 2nd stage of the project will print artificial lung tissue with integration of airway, compared with human cell self-assembly on human whole organ scaffolds. Histological, transcriptomic and protein biomarker based profiling would be used to compare artificial tissue generated using miniaturised scaffolds to whole donor tissue.
(iii) Functional studies of miniaturised artificial tissue
The tissue generated within this study would be tested using previously described mediators of tissue function (e.g. inhibition of airway mucus production of epithelial cells by simvastatin in a lung tissue model, or inhibition of acetylcholine induced intestinal motility by interleukin 1 beta in in a gut model). The specific functional mediators investigated would be defined based on the outcome of (i) and (ii).