The increasing application of 3D printing technology in the fields of medicine and dentistry is revolutionizing the production of dental implants, prosthetics, and practice models for surgeons. Researchers are transitioning from using plastics and metals to 3D printing with cells that can develop into living human tissues. While fully functional transplantable human organs have yet to be printed, notable advancements are being made in developing human tissue samples for drug testing and exploring ways to overcome biological complexities involved in organ fabrication. This article explores significant milestones achieved by research teams and the challenges they face in creating 3D-printed organs.
Heart Cells and Ear Transplants
To date, scientists have successfully printed mini-organ models and microfluidic tissue systems, commonly referred to as organ-on-chip technologies. These innovations provide valuable insights into human physiological functions. Pharmaceutical companies utilize these models to conduct preliminary drug tests before moving on to animal trials and, ultimately, clinical studies. One research group focused on printed heart cells placed these cells in a bioreactor to assess the cardiac toxicity of a well-known cancer medication, Doxorubicin. They observed a significant decrease in the cells‘ contraction rate following drug exposure.
According to Robby Bowles, a bioengineer at the University of Utah, several firms are exploring the use of 3D printing for creating ears intended for transplantation in children with congenital ear deformities. He praised the initial attempts to incorporate 3D printing technology into medical applications.
Organovo Studies
Recently, researchers developed tissue patches mimicking fragments of particular organs. However, they have yet to reproduce the complexity or cell density of a complete organ. Some studies indicate that even small samples of human tissue could considerably aid patient treatment. Organovo, a company focused on designing 3D-printed liver tissue for human transplants, presented promising results from a prior study showcasing live implantations in a mouse model with genetic liver disease, which exhibited several biomarkers indicating enhanced liver functionality.
Researchers have also made gains in addressing one of the primary challenges in 3D organ printing by successfully creating vascular systems within the printed organs. For example, in the Organovo study, patches implanted in mouse livers received blood flow from the surrounding tissue. However, preparing an entire organ to facilitate blood circulation remains a challenge.
Wyss Institute
In 2018, a team at the Wyss Institute, including Sebastian Uzel and Mark Skylar-Scott, achieved a breakthrough by successfully 3D printing a miniature beating heart chamber with integrated blood vessels. Days after the framework was produced, Uzel expressed his astonishment and excitement upon finding tissue that was actively beating when he returned to the lab.
The team employed an embedded printing approach rather than layering the veins in a traditional manner. Their method allows for direct deposition of materials into a matrix, enabling researchers to create “free-form 3D” structures, as noted by Skylar-Scott. In this case, the matrix comprised the cell material that formed the heart chamber. The viscous gel used in the process guided the cells, crafting a network of channels. After completing the printing, heating the combination solidified the cell matrix while liquefying the gel, clearing space for blood flow.
Challenges
Despite notable progress in 3D organ printing, scientists stress that they remain “far away” from producing more complex tissues and organs suitable for transplantation into living organisms. Many researchers aspire to reach this goal soon, as noted by Bowles. According to the United Network for Organ Sharing, over 112,000 individuals in the U.S. are currently awaiting organ transplants, with approximately 20 patients dying every day while on the list.
Bioengineers have long aimed to construct 3D structures capable of carrying stem cells that can evolve into organs. One reason for the difficulties, as Bowles explains, is that traditional methods „largely do not allow for controlling the arrangement of gradients and patterns within the tissue.“ He also emphasized the lack of control over the positioning of cells in these constructs, whereas 3D printing potentially allows for precise spatial organization, which could guide better organ development.
Another critical aspect is that 3D-printed organs must be composed of cells that the patient’s immune system recognizes as its own to minimize the risk of rejection and the need for immunosuppressive medications. Producing 3D-printed organs from patient-specific induced pluripotent stem cells is conceivable; however, the challenge lies in achieving the differentiation of the cells into the specific mature types required to build a particular organ. Bowles notes the difficulty in harmonizing complex cellular patterns with biomaterials to replicate the varying functions of different tissues and organs.
Potential Solutions for the Future
To successfully recreate the in vivo patterns seen in natural tissues, scientists must explore additional methods. They could print cells alongside molecular signals and gradients within hydrogels or other environments to stimulate the cells into organizing themselves into life-like organs. Notably, 3D printing can also facilitate the fabrication of these hydrogels.
Meanwhile, the advancement of tissue 3D printing contributes to enhancing basic and clinical research on human physiology. Despite the ongoing challenges, this technology holds vast potential for organ fabrication, paving the way for life-saving transplants for patients. The continuous evolution of 3D printing demonstrates encouraging outcomes that could one day prove instrumental in treating individuals with critical health conditions.
