A 3D printed liver is a laboratory-created biological structure that mimics the human liver, produced using advanced additive manufacturing techniques. This technology involves building up layers of biological materials, including living cells, to form a three-dimensional object, replicating the complex architecture and functions of a natural liver.
Addressing Organ Shortage and Research Needs
The development of 3D printed livers is largely driven by the severe global shortage of organs for transplantation. Liver disease is responsible for approximately 2 million deaths annually, making liver transplantation a life-saving treatment for many. In 2023, while 10,659 liver transplants were performed in the United States, 9,745 candidates were still waiting. The lack of suitable donor organs means many patients face long delays, and some may not receive a transplant.
Beyond transplantation, 3D printed liver models address a significant need in medical research for improved models for drug testing and disease study. Traditional methods, such as two-dimensional cell cultures or animal models, often do not accurately reflect the complex environment and functions of a human liver. More physiologically relevant 3D structures can provide a better platform to test drug toxicity and efficacy, potentially accelerating drug development and reducing reliance on animal testing. These models also allow researchers to study liver diseases, such as fibrosis or cancer, in a controlled environment, leading to a deeper understanding of disease progression and potential treatments.
The Science of Bioprinting
The creation of a 3D printed liver relies on bioprinting, a specialized process similar to traditional 3D printing but using biological materials. A fundamental component is “bio-ink,” a material composed of hydrogels and living cells. Bio-inks provide a supportive environment for cells, allowing them to maintain viability and function. Hydrogels like alginate, collagen, gelatin, and fibrin are commonly used for their biocompatibility and ability to mimic the natural extracellular matrix.
Multiple cell types are combined within these bio-inks to mimic the liver’s intricate cellular composition. Key cell types include hepatocytes, the liver’s main functional cells, and endothelial cells, which line blood vessels. Fibroblasts and hepatic stellate cells are also included as supporting cells to create a more realistic tissue structure and promote cell interactions. The precise arrangement of these cell types is crucial for replicating the liver’s complex microarchitecture, including its hexagonal lobule structure.
The bioprinting process involves depositing layers of bio-ink to build the desired three-dimensional structure. Different bioprinting techniques exist, such as inkjet, extrusion-based, and laser-assisted bioprinting, each offering varying levels of precision and speed. Some methods involve printing cell “spheroids” or clumps of cells, rather than individual cells, which can help maintain cell contact and functionality. The goal is to construct a scaffold that supports cell growth and organization, mimicking the liver’s complex internal structures and functions.
Current Capabilities and Applications
3D printed liver models currently make significant contributions in several research and testing applications. One application is drug toxicity screening, assessing the safety of new pharmaceutical compounds. By providing a more physiologically relevant environment than conventional 2D cell cultures, these models offer more accurate predictions of drug effects on the human liver, potentially reducing animal testing and accelerating drug development. Some commercially available models, like the exVive3D, incorporate primary hepatocytes, hepatic stellate cells, and endothelial cells for comprehensive drug assessment.
Another use is disease modeling, replicating various liver conditions in a laboratory setting. This allows for detailed study of disease progression, such as fatty liver disease or fibrosis, and enables testing of new therapeutic strategies. Bioprinted liver tissues can mimic liver fibrosis and hepatocellular carcinoma, offering a platform to investigate disease mechanisms and evaluate drug efficacy.
3D printed liver models hold promise for personalized medicine. Using a patient’s own cells, patient-specific liver models can be created. These tailored models allow for individualized drug screening, predicting how a patient responds to medication or treatment. While still largely an aspirational goal for full organ transplantation, the ability to create patient-specific tissues for testing purposes represents a significant step towards more personalized healthcare approaches.
Overcoming Hurdles to Full Organ Function
Achieving fully functional, transplantable 3D printed livers presents several complex hurdles. One challenge is vascularization: creating a dense network of blood vessels within the printed tissue. Without a robust vascular system, cells deep within the printed organ cannot receive sufficient oxygen and nutrients or remove waste, limiting the construct’s size and viability. Researchers are exploring methods like using sacrificial bio-inks to create channels that blood vessels can form within, or directly printing vascular structures with high precision.
Ensuring cell viability and proper maturation within the printed structure remains another obstacle. Cells need to survive bioprinting and mature into fully functional liver cells that can perform the organ’s metabolic and detoxification functions. Maintaining long-term functionality of these cells in a 3D environment, often mimicking the native extracellular matrix and cellular interactions, is an ongoing area of research. For instance, while initial studies show promising cell viability and function, maintaining these for extended periods (e.g., beyond 30 days) is difficult.
The scale and complexity of a human liver also pose challenges. A fully functional liver is a large organ with a highly organized internal structure, including lobules and multiple vascular systems. Printing an organ of this size with the required cellular density and micro-architectural precision is technically demanding and time-consuming. Current bioprinting technologies are still in their infancy regarding the ability to recreate the macro- and microstructural components of a full human liver.
Beyond creation, long-term functionality and seamless integration with the body’s systems are paramount for potential transplantation. This involves ensuring the printed organ connects to the patient’s existing blood vessels and bile ducts, functions correctly over many years, and avoids immune rejection. Researchers are working towards developing patient-specific organs from a patient’s own cells to reduce the risk of rejection and eliminate the need for immunosuppressive drugs.