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Surgical optogenetic bioprinting of engineered cardiac muscle

Project description

Off-the-shelf in vivo cardiac regeneration solution

Advances in tissue engineering allow the fabrication of cardiac tissue for regenerating a damaged heart or repairing congenital heart defects. However, the culture of cardiac tissue is laborious, necessitating faster alternatives. Funded by the European Research Council, the LIGHTHEART project aims to develop an in vivo cardiac tissue engineering approach that uses induced pluripotent stem cells differentiated into cardiac cells directly on patient’s heart. The strategy employs bioprinting and optogenetic stimulation of proteins expressed at the cell surface to drive cellular assembly, thereby overcoming the need for embedding cells in hydrogels. This disruptive bioprinting solution is expected to advance regenerative and transplantation medicine, bringing hope to millions of people suffering from heart failure.

Objective

Heart failure remains a leading cause of mortality worldwide taking an estimate of 16 million lives each year. Cardiac tissue engineering solutions that can improve the quality of life of those with advanced heart disease have proved challenging so far. Bioprinting is an exciting technology that holds promise to fabricate tissues and organs. Lab-grown engineered cardiac muscle requires at least four weeks to maturate in a bioreactor. In LIGHTHEART, an off-the-shelf solution will be developed for treating injured myocardium in vivo. An unconventional combination of bioprinting and optogenetics will be used to surgically fabricate engineered cardiac muscle directly at the patient’s heart. A surgical bioprinting tool will be constructed to achieve vascularization and cellular architectures as that observed in native cardiac muscle. Induced pluripotent stem cell-derived cardiac cells will be the basis of the bioinspired biomaterial-free ink that will be printed. Optogenetic expression of different light-sensitive proteins at the cell surfaces will be the sole trigger of cellular assembly, thus omitting the need to embed cells in hydrogels or printing in a supporting bath. Surgical optogenetic bioprinting will be first tested ex vivo using a silicone human phantom with a mimicking beating heart, and later in vivo in a large animal model in accordance with the 3R principles. LIGHTHEART opens up new horizons in the way heart failure can be clinically treated and brings hope to patients who are desperately waiting for a heart transplantation. The disruptive nature of LIGHTHEART will unite engineers, surgeons and scientists to change the future of transplantation medicine with modular bottom-up technologies that allow for in vivo tissue and organ restoration or replacement directly at the operating theatre.

Host institution

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Net EU contribution
€ 1 499 705,00
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 705,00

Beneficiaries (1)