Recent advancements in 3D printing have brought us closer to the reality of lab-grown organs, a long-sought goal in organ transplantation. A pioneering method known as co-SWIFT has been developed, allowing scientists to 3D print complex blood vessel networks within living human heart tissue. This breakthrough represents a significant step toward creating fully functional, transplantable human organs.
The development of lab-grown organs has been a critical objective in biomedical engineering, often referred to as the “holy grail” of organ transplantation. Despite decades of research, the challenge of replicating the intricate structures of human organs, particularly their vascular networks, has kept this goal out of reach. However, researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Science (SEAS) have made remarkable progress in this area.
The co-SWIFT (coaxial Sacrificial Writing into Functional Tissue) technique is a novel 3D printing method that enables the creation of vascular networks that closely mimic the structure of natural blood vessels. These networks are composed of a double-layered structure with a collagen-based “shell” and a gelatin-based “core,” which can be infused with smooth muscle cells (SMCs) and endothelial cells (ECs). These components are crucial for the function of blood vessels, as they provide structural integrity and facilitate blood flow.
Paul Stankey, a graduate student at SEAS and the study’s lead author, explained the innovation: “Building on our previous work with the SWIFT method, we developed co-SWIFT to replicate the multilayer architecture of natural blood vessels, making it easier to create interconnected networks that can withstand the pressures of blood flow” .
A core-shell nozzle is at the heart of this innovation, featuring two independently controllable fluid channels. One channel dispenses the collagen-based shell ink, while the other releases the gelatin-based core ink. This design allows for precise control over the size and structure of the printed vessels. The nozzle can penetrate previously printed vessels, creating branching networks that are essential for oxygenating human tissues and organs.
The ability to vary the vessel size during printing, by adjusting the speed or ink flow rates, adds another layer of customization, making the process adaptable to different tissue types and patient-specific requirements. This adaptability is crucial for replicating the dense, fibrous structure of living muscle tissue, which is often challenging to achieve.
To validate the co-SWIFT method, the research team first printed the multilayer vessels into a transparent granular hydrogel matrix. They later used a porous collagen-based material called uPOROS, which closely mimics the structure of living muscle tissue. In both cases, the printed vessels successfully formed branching networks, demonstrating the method’s potential for creating functional vascular systems in lab-grown tissues .
The researchers took their work a step further by integrating living cells into the printed vessels. They infused the shell ink with SMCs, which form the outer layer of blood vessels, and perfused ECs, which line the inner layer, into the vasculature. After seven days of perfusion, both cell types remained viable and formed functional vessel walls. This resulted in a threefold decrease in the permeability of the vessels, indicating a significant improvement in their functionality compared to vessels without ECs.
The ultimate test of the co-SWIFT method came when the team applied it to living human heart tissue. They constructed cardiac organ building blocks (OBBs) – tiny spheres of beating heart cells – and used co-SWIFT to print a vascular network within this tissue. After removing the gelatin core, they perfused the vessels with ECs and observed that the tissue began to beat synchronously, a sign of healthy and functional heart tissue. The tissue also responded to cardiac drugs, further demonstrating its viability.
Perhaps most impressively, the researchers 3D printed a model of a real patient’s left coronary artery into the heart tissue, showcasing the potential for personalized medicine. This capability could one day enable the creation of patient-specific organs for transplantation, tailored to the individual’s unique anatomy .
Looking forward, the team plans to enhance their method by integrating self-assembled capillary networks with the 3D-printed vessels. This integration would more accurately replicate the microscale structure of human blood vessels, further improving the function of lab-grown tissues.
Dr. Donald Ingber, Wyss Founding Director, praised the team’s achievements, stating, “Engineering functional living human tissues in the lab is an incredibly challenging task, but this research proves that we can build better blood vessels within living heart tissues. I look forward to seeing how this work progresses toward the ultimate goal of implanting lab-grown tissues into patients” .
The co-SWIFT method represents a major breakthrough in the quest to create lab-grown organs. By successfully 3D printing vascular networks within living human heart tissue, this technology brings us closer to a future where fully functional, transplantable organs can be grown in the lab. The potential for personalized medicine, where organs are tailored to individual patients, is now within reach, thanks to these innovative advancements in 3D printing and tissue engineering.
Reference:
- Stankey, P.P., Kroll, K.T., et al. (2024). Embedding Biomimetic Vascular Networks via Coaxial Sacrificial Writing into Functional Tissue.
