4D bioprinting shape-morphing tissues using phototunable supramolecular hydrogels

Projektinformationen

morphoPRINT

ID Finanzhilfevereinbarung: 101077900

DOI

10.3030/101077900

EK-Unterschriftsdatum 22 November 2022

Startdatum 1 Mai 2023

Enddatum 30 April 2028

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

€ 1 499 906,00

EU-Beitrag

€ 1 499 906,00

Koordiniert durch

UNIVERSITY OF GALWAY
Ireland

Periodic Reporting for period 1 - morphoPRINT (4D bioprinting shape-morphing tissues using phototunable supramolecular hydrogels)

Berichtszeitraum: 2023-05-01 bis 2025-10-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Heart failure affects over 64 million worldwide and is the leading cause of death globally. While heart transplantation offers a viable solution, there is a critical shortage of suitable donor organs. Consequently, there is an urgent need for regenerative therapies that can strengthen the failing heart. Bioprinting, the precise layering of cell-containing bioinks into 3D tissue constructs, holds immense promise for creating lab-grown heart tissue from a patient's cells. However, despite this progress, current bioprinted heart tissues often lack the structural and functional maturity of adult heart tissue, leading to significantly weaker contractile forces. This limits their potential as implants that can strengthen or remuscularise a diseased heart.

To overcome these limitations, the morphoPRINT project is developing new approaches to organ bioprinting inspired by how organs naturally form during embryogenesis. During native embryonic development, organs emerge through highly dynamic processes driven by complex shape transformations that sculpt their final shape, composition, and function. With this in mind, the overall project goal is to develop a hydrogel platform that can spatially control 4D shape-morphing in bioprinted tissues and utilise this platform to re-engineer morphogenetic shape changes that sculpt the tissue into a more mature form. The central hypothesis is that recapitulating 4D shape-morphing in bioprinted tissues will enhance structural and functional maturity compared to static controls. The project has three main objectives. The first is to develop phototunable hydrogels that can be used to direct the programmable shape-morphing behaviours in bioprinted tissues. The second objective is to utilise this hydrogel platform to bioprint heart tubes that undergo embryonic-like cardiac looping into an early 4-chamber structure. The third objective is to explore how these shape-morphing behaviours impact the structural and functional maturation of bioprinted tissues compared to static controls.

Altogether, morphoPRINT will establish a ground-breaking approach to bioprinting where organ rudiments proceed through series of programmed shape changes to sculpt their final shape, composition, and function. This will provide a new platform for enhancing the structural and functional maturity of bioprinted heart tissues. This will accelerate their translation into effective implants for tissue repair and enable their use as predictive platforms for drug screening, bringing us closer to new treatment options for heart failure.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

To date, we have developed phototunable support hydrogels that can be used for embedded bioprinting of tissue constructs. The rheological and viscoelastic properties of these hydrogels have been optimised so that they can support the growth and morphogenesis of organoids and bioprinted tissues derived from induced pluripotent stem cells (iPSCs). It has also been demonstrated that the mechanical properties of these hydrogels can be modulated using light. The impact of cell phenotype (e.g. proliferative, non-proliferative, or contractile) on shape-morphing in organoids and bioprinted constructs has also been characterised. Additionally, we have also investigated how the viscoelastic properties of support hydrogels can impact such cell-mediated shape-morphing behaviours. For example, more viscous hydrogels can better support volumetric growth of organoids and bioprinted tissues. We have also explored how shape-morphing can impact iPSC-cardiomyocyte differentiation and maturation in bioprinted heart tissues. These results demonstrated that morphing can accelerate tissue maturation trajectories compared to static tissue controls. Finally, our collaborators have developed a computational finite element model that can predict the shape-morphing of bioprinted tissues within our support hydrogels. The next phase of the project will focus on bioprinting heart tube models that undergo embryonic-like looping into a four-chamber structure.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Current approaches to organ bioprinting typically focus on creating static tissue constructs that recapitulate the final shape of the organ. This bypasses the developmental processes in which embryonic tissues undergo dynamic structural shape changes that sculpt their final shape, composition, and function. morphoPRINT is advancing beyond the state-of-the-art by developing a novel platform for programming 4D shape-morphing behaviours in bioprinted tissues.

Our results to date demonstrate that support hydrogels with more viscous properties enhance shape morphing of organoids and bioprinted tissues, whereas more elastic hydrogels constrain morphing. Importantly, our results also demonstrate that cell-mediated shape-morphing can accelerate the differentiation and maturation of bioprinted heart tube constructs. Given that the limited maturity of bioprinted heart tissues has been a significant challenge in the field, this represents an advance beyond the current state-of-the-art.

Furthermore, our computational finite element models also effectively predict 4D tissue shape-morphing, providing a framework for the predictive design of shape evolution in bioprinted tissues for the first time. Our bioprinting platform, coupled with this predictive FE modelling framework, offers a powerful tool for designing and fabricating issues that undergo programmable shape-morphing to sculpt their final form.