Third party funded individual grant
Start date : 01.01.2019
End date : 31.12.2020
Additive Biomanufacturing (ABM) has stimulated a whole new research direction by the combination of tissue engineering and additive manufacturing technologies. Tissue engineering approaches, which originally focused on the repair and restoration of damaged tissue structure and function, are increasingly applied with ABM to produce three-dimensional (3D) cell culture models. ABM can, for instance, be used to engineer physiologically relevant cancer microtissues in the laboratory for drug development and basic research, allowing the acquisition of data with increased predictive value of the human response. Although such cell culture models are emerging as promising tools for disease modelling or drug screening applications, the application of this technology is also coupled with new, yet unmet technical challenges. The current preparation and manufacturing workflow involves tedious manual steps that limit throughput and increase the probability of user error; errors that can potentially manifest as inaccurate results. Moreover, the analysis of 3D models with traditional laboratory equipment and cell analysis methods is challenging or impossible because highly specialized laboratory equipment and assays are required for the analysis of 3D structures. Investigation of matrix remodelling as well as cell function screening are required on a maturation timeline over several days, weeks, or even months in a repetitive and reproducible manner to characterize the suitability of novel biomaterials or cell combinations. Thus, with the advancements of 3D culture models come the engineering challenges to implement adequate readout platforms that also allow high-content and high-throughput screening to ease otherwise tedious bioanalytics methodologies. Up to now, combinatorial screening of 3D biomaterial properties and 3D engineered constructs is limited due to missing technical solutions, such as automated manufacturing and screening systems. Based on the Australian partner’s current focus on tissue engineering principles and the German partner’s expertise on robophotonics and optical engineering, advanced Additive Biomanufacturing Technologies will be designed to successfully translate 3D models into an automated industrial setting with high-throughput capabilities. Such an industrial setting with automated manufacturing workflows and integrated quality control has been termed ‘Industry 4.0’ and is evolving as an emerging field in multidisciplinary bioengineering disciplines.
This project aims to transfer technologies and expertise related to the high-throughput manufacturing and screening process of 3D cell culture models between the Australian team based at the Queensland University of Technology (QUT) and the German partner at the Friedrich-Alexander University Erlangen-Nuernberg (FAU) as well as to establish collaborative projects to work on advanced Additive Biomanufacturing technologies. To exchange knowledge and enable technology transfer, the specific goals of this project are:
1) The established 3D tissue culture platform and know-how on 3D cancer models by QUT will be transferred to FAU to successfully integrate 3D cell culture technologies in FAU’s laboratories. 3D cancer models will be visualized using the recently developed xCell low-cost microscopy environment (http://www.port-a-scope.com) using camera-based automated acquisition, image segmentation and registration, followed by automated pattern recognition and object classification. The technology of the xCell system will be then transferred to the Australian partner to allow long-term microscopical assessment of cell growth and matrix remodelling experiments at both partner locations. Second Harmonic Generation (SHG) multiphoton microscopy will be performed on selected 3D constructs fixed at given time points and transferred to the German labs to assess matrix formation of collagen-I networks by cells, replacing the biomaterial phase.
2) FAU’s expertise on robophotonics and optical screening technology will be introduced to QUT’s team to successfully integrate a camera-based feedback system and design a control system with a web-based interface for QUT’s prototype of an Additive Biomanufacturing Platform. The developed and integrated improvements will enhance the capability and functionality of the prototype to manufacture 3D models in a reproducible manner.
Building upon each other’s expertise and the aquired know-how within this project, an advanced workstation will be designed and engineeed to allow high-throughput drug screening applications using a multimode plate detection system, liquid and viscous handling device, and integrated imaging functionality.