Hidden in the epigastric region of the abdomen concealed by a curtain of peritoneum is a moody, often forgettable little organ. Of course, the term organ is a somewhat generous description for this rather overqualified gland. The pancreas has its own set of rules as it mischievously lurks behind the stomach waiting for its cue for chaos.
In a moment of theatrical exaggeration, it can go from completely forgettable to a life-changing, painful calamity. Or by a more subtle route, it may suddenly cease to function without warning. This is why the cautionary advice of “do not to mess with the pancreas” resonates throughout operating rooms.
From uncontrollable diabetes to painful pancreatitis to the feared pancreatic cancer, pathologies of the pancreas have long been uphill struggles in medicine. Often diseases of the pancreas are severe and intractable. Even the most intense of treatments, including surgical resections and combined chemotherapies, eventually fail to treat the various mishaps of this organ. But imagine, what if we could instead bypass the need to target the actual pathophysiology of the pancreas?
Consider if, maybe only in the future, we could design a pancreas not defined by its volatile temperament.
The concepts of bionic humans and cyborgs have been familiar in the genres of science fiction and fantasy. For anyone who has struggled with a copying machine, the idea of printing anything beyond a 2-dimensional paper might seem unrealistic.
However, the technology necessary for 3D-printed organs first emerged 37 years ago, in 1983, when Charles Hull invented stereolithography, more commonly known as 3D printing today. This new technology consisted of a printing method that used a laser to solidify polymer material emitted from a nozzle.
Stereolithography set the foundation for the future of 3D-printed organs. From data coding for physical features of an organ structure, a 3D printer could translate the data into the organ’s physical structure. The first-ever 3D-printed organ was a bladder in 1999 at the Wake Forest Institute of Regenerative Medicine. An artificial scaffold was first printed, followed by cells being seeded onto the framework. Astoundingly, the recipient of the bladder had no major complications even 10 years later.
The pancreas is one of the latest, though not often considered, targets of 3D printing. Type 1 diabetes is one of the most common yet most challenging pancreatic illnesses to manage and can result in severe complications in many other organ systems.
In the pathophysiology of type 1 diabetes, pancreatic islets of Langerhans, a group of beta cells that secrete insulin, fail to function appropriately, which results in hypoglycemic episodes. From comorbid damages to the eyes, kidney, and heart, managing diabetes requires lifelong treatment, and not all patients respond well.
Currently, more than 40 million people globally have type 1 diabetes, and the WHO predicts that by 2030, diabetes prevalence, morbidity, and mortality will only continue to increase.
While insulin injections and pumps are common in type 1 diabetes management, the only potential cures are pancreas transplantation and pancreatic islet transplantation. Unfortunately, transplants are at high risk for organ rejection and rely on availability from deceased organ donors, not to mention surgical risks.
Only recently, researchers began considering novel ways to combat type 1 diabetes using 3D printing. On March 14th, 2019, the first bionic pancreas was printed. A group of researchers in Warsaw working for the Polish Foundation of Research and Science Development created the prototype measuring 3x3x5 cm that was also vascularized. Not only was the pancreas physically printed, but it also had functional capabilities of insulin secretion responding to glucose.
With successfully bio-printed pancreatic islets and vessels with endothelial cells, the 3D-printed pancreases were quickly moved on to animal testing on mice. Ideally, from this study that is currently being conducted, a mechanism of how vasculature develops between the bio-printed organ and the host’s body will be elucidated. Eventually, stem cells will be used to develop alpha and beta cells (glucagon and insulin-producing cells, respectively) to replace the pancreatic islets.
From the ongoing research, a technique to create a 3D-printed pancreas for implantation can be developed. Using a 3D bioprinter named “BioX” from Swedish company, Cellink, the 3D-print would actually be a scaffold that would support a collection of alpha and beta cells. These cells would be cultured from the patient’s own stem cells retrieved from a biopsy that will function as a “bio-ink.” Given that the cells originate from the patient, there will be no need for immunosuppression after implant. The immunocompatibility is a major benefit of 3D printed implants over transplants from deceased organ donors. Regardless, attention will still be necessary to ensure that the cells and the bio-print are compatible.
Clinical trials testing the efficacy of 3D-printed pancreases are still concepts of the future. Nevertheless, research is bringing that distant hope closer to reality. Magnetic resonance imaging and CT scans have already revealed that the vascular system of the bionic pancreas is exactly as it was designed to be.
Blood vessels have been designed with a diameter of 1 mm. Researchers would like to reduce the size even more to resemble the natural vessels to improve the perfect integration of the transplant into the human body. As the previously mentioned mice studies are showing success so far, the project will then likely be conducted on pigs prior to moving onto human transplants.
A fully functional 3D-printed pancreas was aimed to be developed by 2022. Of course, due to the recent COVID-19 pandemic, it is unclear whether this goal can still be met. However, the future of medicine in regards to the pancreas and treating diabetes is bright. After the animal and clinical trials, the possible FDA-approved bionic pancreas is predicted to become a permanent, functioning piece of the human body. Unlike insulin injections and pumps, patients will no longer have to intervene as much, if at all, in their management of diabetes. While the pancreas will be artificial, its functioning is predicted to be physiologically comparable to a natural pancreas.
For many, the diagnosis of type 1 diabetes leads to endless concerns and anxiety, and unfortunately for some, comorbidities are unavoidable. But the potential of designing fully functional pancreases, or any organ, in fact, is to target the pathologies that remain formidable.
Therefore the question is, what else can be treated by 3D printing?
Pancreatic cancer, for example, has a 5-year survival rate of 9 percent for all stages combined, according to the American Cancer Society. In patients in which the cancer has not spread beyond the pancreas, patients can undergo resection, which can improve 5-year survival up to 37 percent if the tumor is fully removed. Even with resection, however, pancreatic cancer remains a challenging disease to treat.
Already there has been the application of 3D printing to pancreatic cancer treatment. For local chemotherapy, 3D-printed drug delivery patches have been used target treatment with greater specificity to pancreatic tumors.
Another approach has been using 3D printing to study how pancreatic tumor microenvironments impact pancreatic cancer development. Patient-specific in vitro 3D models have been designed to study extracellular and cellular aspects of pancreatic cancer. Even so, fully functioning 3D-printed pancreases have yet to be applied to cancer treatment which raises the question of whether it is possible.
At the same time, it is important to step back and consider limitations to such an advancement. When would using a 3D-printed pancreas, or any organ, be considered a necessary intervention as opposed to an optional one?
Whereas, for example, type 1 diabetes could be cured by a 3D-printed pancreas, injections and routine management might still be preferred due to less surgical risk and possibly more cost-efficient. Furthermore, what assessments might be used to determine who would be an appropriate candidate for 3D-printing therapies? Assumedly, medical limitations would affect who could be treated effectively. Predicting the feasibility of 3D printing is challenging to do at the moment, given its infancy. Still, it is necessary to consider that such a treatment may not be accessible to all patients equally and readily.
The capabilities of 3D-printing technologies are new to medicine but have implications for manufacturing tissues, organs, implants, prosthesis, surgical simulation models and even medicines. The thought of a bionic organ, much less a pancreas, was once just a topic considered for science fiction but now are becoming a reality full of potential possibilities. With continued advancements in technology, it would seem that no pathology would be left untouched by future remedies.
If, after all, we can tame the infamous, moody pancreas, then what can medicine not do?
Thomas L. Amburn is a medical student.
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