The main objective of 4-DBR is to generate a new implantable 4D-bioprinted reconstructed brain that contains a vascular system, specific human neurons that will be stimulated by a customized optogenetic system to bypass the bottlenecks in cell-based therapies for neurodegenerative disorders.
To achieve the objective of 4-DBR, four specific aims has been targeted:
1. To develop 3D transplantable reconstructed brain-based therapeutic strategies.
We will improve existing techniques and protocols to obtain all the components of the personalized reconstructed brain. These include a variety of brain cells, the cellular components of the Blood Brain Barrier (BBB) and brain extracellular matrix (ECM) to develop our own bioinks.
2. To set up 4D bioprinting technologies allowing a rapid and standardized production of reconstructed brains.
The Consortium will develop the scaffold to sustain the different components previously described, through next-generation bioprinting
3. To develop and bioprint a bio-photonic system.
We will include in the bioprinted reconstructed brains an optogenetic system. This system, linked through wireless technology, will leak light at several points to promote cell maturation once the structure is implanted.
4. To validate reconstructed brains-based therapeutic strategies in a mouse model.
The functionality of the highly innovative reconstructed 4D mini-brain will be tested in vivo, specifically in transgenic Huntington's disease mouse models.