The quest to create functional human organs outside the body for transplantation has long been a tantalizing dream in the field of medical science. Despite the challenges, recent breakthroughs have brought this ambition closer to reality. A collaborative effort between researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences has yielded a groundbreaking method for 3D printing vascular networks that could revolutionize organ fabrication.The Breakthrough in Vascular Network PrintingThe team’s innovative approach focuses on creating interconnected blood vessels that closely mimic the structure of natural blood vessels. These vascular networks consist of a “shell” made of smooth muscle cells and endothelial cells that encase a hollow “core” for fluid circulation, all integrated within human cardiac tissue. This development represents a substantial advancement toward the fabrication of implantable human organs.Previously, the researchers developed a 3D bioprinting technique known as “sacrificial writing in functional tissue” (SWIFT), which allowed for the creation of hollow channels within living cellular matrices. Their latest work, published in the journal Advanced Materials, introduces an enhanced method called coaxial SWIFT (co-SWIFT). This technique mimics the multilayered architecture of native blood vessels, which is crucial for forming an interconnected endothelium and withstanding the internal pressure of blood flow.Innovative Core-Shell Nozzle DesignCentral to this breakthrough is a unique core-shell nozzle equipped with two separate fluid channels for the printing materials. One channel is dedicated to a collagen-based shell ink, while the other is for a gelatin-based core ink. The design allows the core chamber to extend slightly beyond the shell chamber, enabling it to penetrate previously printed vessels and create essential interconnected branches for tissue oxygenation through perfusion.During the printing process, researchers can adjust the vessel size by modifying the ink flow rates or printing speed, providing flexibility in design. The team first demonstrated the co-SWIFT method by successfully printing multilayer vessels within a clear hydrogel matrix and a novel material called uPOROS, which mimics the fibrous structure of muscle tissue. These experiments resulted in successful prints of branching vascular networks in cell-free matrices.Creating Perfusable VasculatureAfter establishing the vascular networks, the next step involved heating the matrix to crosslink the collagen in both the matrix and the shell ink while simultaneously melting away the gelatin core ink. This process left behind a hollow, perfusable vasculature. To enhance functionality, the researchers infused the shell ink with smooth muscle cells, which are characteristic of the outer layers of human blood vessels. Following the removal of the gelatin core, endothelial cells were perfused to form the inner vessel layers.After just one week, the infused cells remained alive and functional, successfully forming vessel walls. In a significant test of their technique, the researchers integrated these 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. Remarkably, the integration of these systems led to OBBs that began to beat synchronously after five days, demonstrating the formation of functional and healthy heart tissue. The researchers further validated their method by observing responses to typical cardiac drugs.Personalized Medical ApplicationsThe team also showcased the potential for personalized medical applications by creating a 3D-printed model of a patient's coronary artery vasculature. This ability to tailor 3D-printed vascular networks to individual patients opens new avenues for personalized medicine and tailored treatment strategies.Looking ahead, the researchers plan to focus on developing capillary networks that can integrate with these 3D-printed vessels, further mimicking the microscale structure of human tissues and enhancing the functionality of lab-grown organs.Challenges and Future Prospects“Engineering functional living human tissues in the lab is difficult,” 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.” His remarks highlight the significant challenges that lie ahead, but also the promising potential of these advancements.The journey toward implantable lab-grown tissues for patients continues, and this groundbreaking work represents a pivotal step forward in the field of regenerative medicine. As researchers refine their techniques and expand their understanding of tissue engineering, the dream of functional organ transplantation may soon be within reach, transforming the landscape of medical treatment and improving countless lives.ConclusionThe advancements in 3D bioprinting, particularly the development of coaxial SWIFT for vascular network fabrication, demonstrate the innovative spirit of scientific inquiry and its potential to overcome longstanding challenges in organ transplantation. By harnessing the power of bioprinting technology, researchers are paving the way for a future where lab-grown organs become a reality, offering hope to patients in need of transplants and reshaping the future of healthcare.
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