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Better Bioprinting by Light-sheet Lithography

Periodic Reporting for period 1 - B-BRIGHTER (Better Bioprinting by Light-sheet Lithography)

Período documentado: 2022-10-01 hasta 2023-09-30

Bioprinting is considered the most promising method to produce functional engineered tissues with physiological properties. Successful tissue engineering will open research avenues for drug testing and therapeutic and will therefore raise much interest not only in the academia, but also pharma and clinical sectors. Current bioprinting methods are limited by combinations of insufficient speed, spatial resolution and cell viability. Since these technologies often suffer from poor spatial resolution and inability to control biomechanical properties, they fail to mimic the heterogeneous nature of native tissues. B-BRIGHTER aims to develop a novel bioprinting technology able to produce engineered tissues with high spatial resolution at high printing speed using an original top-down lithography approach. In contrast with current bottom up, layer-by-layer bioprinting methods, B-BRIGHTER aims at ultra high-speed digital light-sheet illumination strategy to selectively photo-crosslink cell-laden hydrogels mimicking specific tissues, in confined voxels and produce three-dimensional complex geometries. Previous advances from the BRIGHTER project will be extended by building complex bioengineered skin, cornea and gut tissue models, all of which represent pioneering examples for bioengineering, and its application for cell therapy, drug discovery and toxicology. Together with the work on patterning technology, bioink and application, a basis will be established for formulating a valid business case for a bioprinting product. The work on exploitation activities will ultimately result in a go-no go decision for the industrialisation of a bioprinting product and a commercial path forward. Ultimately, the goal of the B-BRIGHTER project is to provide a radically new bioprinting technology to boost the performance of various engineered tissues which in turn will promote improved healthcare opportunities, as well as business and employment advances in the European Union and beyond.
The B-BRIGHTER project can be seen to have four main goals, namely producing a cost-effective and repeatable bioink, producing two prototype bioprinters, that these bioprinters can be used to produce bioprinted tissue, and finally that this tissue provides data that can be used in the development of an effective business case based on the light-based bioprinter. These overarching goals will be achieved through work undertaken in all of the work packages, as described in detail below. At a macroscopic level, the work toward achieving the four main goals can be summarised as follows.

Cost effective bioink manufacture – The development of the bioink is led by CED.

Two LS Bioprinter prototypes are operational – Work is focussed at GUF and MYC to convert a laboratory-based device built on an open optical table to a more compact device with an acceptable footprint to be used in a laboratory environment. The device will be installed initially at the project partners IBEC-CERCA and TECH. The work is led by GUF, but has been supported by MYC and one of its experienced mechanical designers. A fundamental optical design that implements multiple patterning beams that would decrease the patterning time linearly with the number of beams. The multi-beam implementation will not be used in the two bioprinters that will be built during the project.

LS Bioprinter and bioinks produce bioprinted tissues – The main work of printing the tissue types that have been identified for the B-BRIGHTER project, namely gut, skin and cornea, is being prepared at present while waiting for the delivery of the two bioprinters during 2024. Preliminary work is being undertaken by IBEC-CERCA and TECH with the existing printing device at GUF to facilitate the coming work with the new bioprinters.

Bioprinting data valid for the business case – A significant amount of work has been performed to shape the business case for a valid business offering. This includes interacting with stakeholders, utilising business case development strategies for deep tech innovations, and carrying out workshops within the project. Further work will be carried out to better understand existing and future users of bioprinters will require with respect to bioprinter specifications, such as resolution, printing speed, utilisation time, et cetera.
Work in the project enables real-time monitoring of hydrogel crosslinking using fluorescent recovery after photobleaching (FRAP) and brightfield imaging as well as in situ light sheet imaging of cells. Full-thickness skin constructs of high viability displayed characteristics of both epidermal and dermal layers and remained.

Work continues in the project to produce new bioprinters, as well as developing a viable business case. Work with the business case of the technology requires further development of the relevant use cases, interactions with existing and possible future users. Support concerning regulatory aspects is being identified, as is mentoring concerning how to access funding opportunities for a proposed spin-off.
B-BRIGHTER schematic