Periodic Reporting for period 2 - VOLUME-BIO (Volumetric light-driven bioprinting capturing complex physiological shape, size and function in artificial tissues and organoids)
Okres sprawozdawczy: 2022-07-01 do 2023-12-31
Achieving this primary goal, the pioneering work of VOLUME-BIO comprises: 1) Establishing a new versatile light-based bioprinting technology, to overcome the limits of current bioengineering and printing methods, which preclude the generation of fully functional human tissues; 2) Developing a portfolio of materials compatible with the VOLUME-BIO approach, with tunable mechano-biochemical properties, capable to safely embed cells and drive their maturatio; 3) Creating a platform to probe the fundamental question of how the degree of complexity of the engineered organoids (multicellularity, architecture, ECM stiffness and 3D morphogen patterns) influences the emergence of tissue-level functions, in contrast to simplified, less organized models. 4) Introducing perfusable vascular networks to permit long-term survival of biofabricated tissues. 5) Presenting a proof-of concept of functionality of bioprinted organoids, laden with cells displaying diverse characteristics and engineering requirements, specifically, as bio-factories expressing the hematopoietic function of bone.
1) A novel technique for bio-friendly refractive index matching, to enable high resolution light-based bioprinting, also in presence of high cell concentrations.
2) The creation of centimeter-scale with micrometer-scale resolution environments to grow and steer the functionality of bioprinted organoids.
3) We built a new set of fully chemically defined, and bioprintable hydrogels in which multiple types of organoids can be expanded
4) We demonstrated for the first time the possibility to use a single-photon technology to position bioactive molecules and morphogens with micrometer-scale resolution, in any desired 3D pattern, across centimeter-large hydrogels, therefore steering cell behavior in a spatially-controlled fashion
5) We have developed a new strategy to build reinforced, cell-laden hydrogels, converging volumetric bioprinting and melt electrowriting
5) We developed a new modular, granular hydrogel bioresin for volumetric and light-based printing, which allows multiple cell types to thrive, and combines the strengths of extrusion and volumetric bioprinting in a single process
7) We developed stromal vascular organoids to support the homing and culture of human hematopoietic stem cells
We expect that we will deliver the following results before the finalization of the project:
1) Generating a complex bone marrow-niche system for the homing and sustained culture of human hematopoietic stem cells
2) Gaining fundamental insights into what drives HSC maintenance of multipotency, survival and differentiation
3) Creation of centimeter-sized and vascularized organoids sized organs that will remain viable in vitro for >4 weeks while sustaining long-term hematopoietic stem cells, the cell type most needed for reconstituting all blood lineages during stem cell transplantation therapies