The goal of generating functional human organs outside the body for transplantation has long captivated the field of medical science, but has largely remained out of reach. Recent advancements, however, may have now brought this ambition significantly closer to reality.

A collaborative effort by researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering (Cambridge, MA, USA) and the John A. Paulson School of Engineering and Applied Sciences (SEAS, Cambridge, MA, USA) has led to the creation of a groundbreaking method to 3D print vascular networks. These networks feature interconnected blood vessels that are lined with a “shell” of smooth muscle cells and endothelial cells encircling a hollow “core” where fluid can circulate, all embedded within human cardiac tissue. This structure closely mirrors that of natural blood vessels and marks a substantial step forward in the potential to fabricate implantable human organs. In their previous work, the same team had developed a new 3D bioprinting method, called “sacrificial writing in functional tissue” (SWIFT), for patterning hollow channels within a living cellular matrix. In their latest work published in Advanced Materials, the team built on this method to introduce coaxial SWIFT (co-SWIFT) that mimics the multilayered architecture typical of native blood vessels, enhancing their ability to form an interconnected endothelium and withstand the internal pressure of blood flow.

The breakthrough involves a unique core-shell nozzle equipped with two separate fluid channels for the printing “inks”: one for the collagen-based shell ink and another for the gelatin-based core ink. The core chamber of the nozzle protrudes slightly beyond the shell chamber, allowing it to penetrate a previously printed vessel to create interconnected branches essential for tissue oxygenation through perfusion. Adjustments in vessel size during printing can be achieved by altering the ink flow rates or the printing speed. The team first demonstrated the co-SWIFT method by printing multilayer vessels within a clear hydrogel matrix and a novel matrix called uPOROS, which mimics the fibrous structure of muscle tissue. These experiments led to successful prints of branching vascular networks in cell-free matrices.

Following this, the matrix was heated to crosslink the collagen in both the matrix and the shell ink, and to melt away the gelatin core ink, leaving behind a hollow, perfusable vasculature. Advancing further, the researchers infused the shell ink with smooth muscle cells, typical of the outer layers of human blood vessels, and after removing the gelatin core, endothelial cells were perfused to form the inner vessel layers. After a week, these cells were alive and functional, forming vessel walls. In the most significant test of their technique, the researchers integrated their printed vessels into densely packed cardiac organ building blocks (OBBs)—clusters of beating human heart cells. They 3D-printed a biomimetic vessel network into this cardiac tissue, removed the core ink, and perfused the vessels with endothelial cells. The integration of these systems culminated in OBBs that began to beat synchronously after five days, demonstrating functional and healthy heart tissue. Responses to typical cardiac drugs further validated their method. The researchers even created a 3D-printed model of a patient's coronary artery vasculature, showcasing the potential for personalized medical applications. Future efforts will focus on developing capillary networks that integrate with these 3D-printed vessels to better mimic the microscale structure and enhance the functionality of lab-grown tissues.

“To say that engineering functional living human tissues in the lab is difficult is an understatement,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. “I’m proud of the determination and creativity this team showed in proving that they could indeed build better blood vessels within living, beating human cardiac tissues. I look forward to their continued success on their quest to one day implant lab-grown tissue into patients.” 

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