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.
