3D Bioprinting of Patient-Derived Vascularized Cardiac Spheroids for Heart Tissues

Background and Aim: 3D bioprinting of tissue and organs from humanstem cells is a promising alternative to promote tissue regeneration.Methods: We have generated a bio-ink for the bioprinting of the humanheart by co-culturing in hanging drops human primary or iPSC-derivedcardiomyocytes, endothelial cells and fibroblasts at ratios approximatingthose present in vivo.Results: These microtissues are called vascularized cardiac spheroids (or VCSs ) as their cellular organization, extracellular matrix andmicrocapillary network recapitulate the microenvironment of the humanheart tissue. VCSs respond to both physiological and pathologicalstimulation in vitro and have been employed to investigate molecularand cellular mechanisms regulating cardiotoxicity, angiogenesis,fibrosis and regeneration of the heart. Loaded into the nozzle of the 3Dbioprinter, VCSs are used as building blocks for the bioprinting of humanheart tissues. To bioprint heart tissues with defined geometries, VCSs aredeposited layer-by-layer within a biocompatible matrix or hydrogel that better recapitulates the human heart microenvironment.Conclusion: 3D bioprinting of a fully vascularized human heart tissueusing VCSs offers a promising alternative to animals and standard cellcultures for drug testing and disease modeling in vitro. Transplantationof patient-specific 3D bioprinted human heart patches from VCSs arecurrently investigated to promote tissue regeneration for cardiovasculardisease patients.

کلیدواژه ها:

bioprinting ، cardiac spheroids ، bio-ink ، personalized therapy ، angiogenesis ، hydrogels