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Engineering Bone Marrow Bioreactors for the Infinite Production of Blood Products

Project description

Scalable, continuously bio-printed bone marrow could create an infinite blood supply

Global demand for blood transfusions far exceeds voluntary donations, with EU shortages growing by around 20 % annually. Cultivating blood-forming stem cells is a potential solution but attempts have failed – these cells rapidly lose their regenerative and differentiative capacities. Hypothesising that these stem cells require the complex signals provided by their natural bone marrow environment, the ERC-funded InfiniBlood project aims to engineer the first bone marrow-mimicking bioreactor. Using its pioneering continuous volumetric bioprinting technology, it will create 3D hydrogel structures at virtually unlimited scale and quantity that replicate the biochemical and physical components stem cells need to self-renew and differentiate. InfiniBlood outcomes could unlock limitless, on-demand production of blood cells for life-saving therapies worldwide,

Objective

Life-saving blood replacement therapies depend entirely on voluntary donations, but demand surpasses supply. In the EU, 25 million blood donations are collected annually, yet shortages persist with about 20% yearly increase in demand. A promising solution is preservation of hematopoietic stem cells (HSC) in the laboratory to provide a limitless, off-the-shelf source of blood cells. In vivo, these HSC, primarily residing in the bone marrow (BM), continuously regenerate blood. Yet, in vitro attempts to recreate this lead to rapid loss of HSC self-renewal and differentiation capabilities. I hypothesize that this is related to the lack of necessary cues of the BM niche created by its highly vascularized extracellular matrix (ECM) where HSC are maintained during adulthood. In InfiniBlood, I will advance Xolography, a new two-colour volumetric manufacturing technology, into a unique continuous bioprinting process to engineer the first BM-like material bioreactor capable of sustaining HSC self-renewal and differentiation for extended periods (months) in vitro.
To achieve this, I will 1)develop BM mini-tissues (organoids) within novel two-colour photoinitiators and viscoelastic hydrogels with functional proteins, thus recapitulating BM ECM properties allowing for guidance of HSC maintenance; 2) engineer perfusion of BM organoids for nutrient and oxygen supply, ensuring long-term HSC maintenance in culture and mature blood cell collection; 3) advance Xolography to continuous bioprinting on a moving belt (roll-to-roll), thus enabling indefinite extension of build volumes, ultimately producing clinically relevant blood cell amounts; and as proof-of-concept, 4) investigate the ability of bioreactor-cultured HSC, to self-renew and differentiate into erythrocytes and thrombocytes. Overall, this ambitious project will engineer novel material bioreactors via the first continuous bioprinting method to unlock infinite blood cell production in vitro to address patient needs worldwide.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-COG

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Host institution

TECHNISCHE UNIVERSITEIT EINDHOVEN
Net EU contribution
€ 1 999 096,00
Address
GROENE LOPER 3
5612 AE Eindhoven
Netherlands
Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 999 096,00

Beneficiaries (1)